A strategy for the targeting of photosensitizers. Synthesis, characterization, and photobiological property of porphyrins bearing glycodendrimeric moieties

DOI: 10.1021/jo102185d

Source and publish data:

Journal of Organic Chemistry p. 2010 - 2028 (2011)

Update date:2022-09-26

Topics:

Authors:

Ballut, Severine

Naud-Martin, Delphine

Loock, Bernard

Maillard, Philippe

Read Full Text PDF DownLoad Join now for total 90,000,000 free articles

Article abstract of DOI:10.1021/jo102185d

This paper describes the conception, synthesis, and characterization of new tetrapyrrolic chromophores bearing glycodendrimeric moieties inducing a potential increase of tumor targeting by a cluster effect. Two families of monoglycodendrimeric photosensitizers bearing three glycosyl units were designed, prepared with an acceptable overall efficiency and characterized by NMR, UV-visible, and fluorescence spectroscopies. The polarity and log P were evaluated by HPLC and the stir-flask method, respectively. The in vitro photoefficiency against two human tumor cell lines was assessed. The presence of the glycodendrimeric group does not appear to increase the tumor in vitro targeting.

Full text of DOI:10.1021/jo102185d

ARTICLE

pubs.acs.org/joc

A Strategy for the Targeting of Photosensitizers. Synthesis,

Characterization, and Photobiological Property of Porphyrins Bearing

Glycodendrimeric Moieties

Sꢀeverine Ballut,^†,‡Delphine Naud-Martin,^†,‡Bernard Loock,^†,‡,§and Philippe Maillard*^,†,‡,§

^†UMR 176 CNRS/Institut Curie, Institut Curie, B^at 110, University Paris-Sud, F-91405 Orsay, France

^‡Institut Curie, Section de Recherches, Centre Universitaire, University Paris-Sud, F-91405 Orsay, France

^§GDR CNRS 3049 “Mꢀedicaments Photoactivables-Photochimiothꢀerapie (PHOTOMED)”, France

S Supporting Information

ABSTRACT:

This paper describes the conception, synthesis, and characterization of new tetrapyrrolic chromophores bearing glycodendrimeric

moieties inducing a potential increase of tumor targeting by a cluster eﬀect. Two families of monoglycodendrimeric photosensitizers

bearing three glycosyl units were designed, prepared with an acceptable overall eﬃciency and characterized by NMR, UV-visible,

and ﬂuorescence spectroscopies. The polarity and log P were evaluated by HPLC and the stir-ﬂask method, respectively. The in vitro

photoeﬃciency against two human tumor cell lines was assessed. The presence of the glycodendrimeric group does not appear to

increase the tumor in vitro targeting.

’ INTRODUCTION

membrane lectin-type receptors. These receptors are over-

expressed in certain malignant cells.^11,12Thus glycoconjugation

can be a potentially eﬀective strategy for targeting photosen-

sitizers toward tumor cells. In the last ten years, we have explored

the eﬀects of the number, the position, and the nature of O- or

S-glycoconjugated moieties on the in vitro photoactivity. Gen-

erally, it has been shown that amphiphilic triglycoconjugated

sensitizers are more phototoxic than either the parent tetra-

pyrrolic or the symmetrical tetraglycoconjugated derivatives.¹³

Recently, we have shown that the presence of a diethylene

glycol linking a monosaccharide as R-mannose or R-galactose

to the macrocycle optimizes the in vitro¹⁴and in vivo¹⁵photo-

activity.

The incorporation of carbohydrates on tetrapyrrolic

macrocyclic cores usable in photodynamic therapy (PDT)

continues to be pursued vigorously by a number of research

teams, particularly during these last two years.^1-3In recent

years, several articles and reviews describing the utility of

porphyrin-based compounds in photodynamic therapy were

published.^4-6In our laboratory, eﬀorts have been focused on

the preparation and in vitro evaluation of the phototoxicity of

a broad series of neutral glycoconjugated tetrapyrrolic macro-

cycles as potential photosensitizing agents for photodynamic

therapy.^7-9In these systems, glycoconjugation modiﬁes

the amphiphilicity of macrocycles and can favor their inter-

actions with the tumor cell membrane.¹⁰Concerning this

latter property, indications are that glycosylation provides the

possibility for speciﬁc interactions of the conjugate with

Received: November 3, 2010

Published: March 01, 2011

2011 American Chemical Society

2010

dx.doi.org/10.1021/jo102185d J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

Figure 1. Structures of dendrimeric and glycodendrimeric porphyrins.

The photodynamic eﬃciency of a photosensitizer was

determined by its cellular uptake and accurate subcellular

localization in tumor cells. The identiﬁcation of transport

mechanisms through the biological membrane was a crux.

This transport could be steered by the action of a membrane

receptor such as lectin or by an active mechanism. It would be

advantageous to use one of these mechanisms for the optimi-

zation of tumor targeting of photosensitizers. In this context,

the use of glycodendrimeric groups as recognition motifs of

lectin is very exciting. It has been widely accepted that

carbohydrate-protein interactions play a crucial role in a

large number of biological processes, such as pathogenic infec-

tions, receptor-mediated endocytosis, inﬂammation, and

metastasis.^16-18Carbohydrates receptors implied in carbo-

hydrate-protein interactions are multisubunit and multi-

valent proteins with many important biological functions.^19-23

Since most proteins possess multiple carbohydrate-recogni-

tion domains and typically exist as oligomeric structures, this

limitation is often overcome through multivalency.²⁴Due

to the weak nature, in the millimolar range, of interac-

tions between single speciﬁc carbohydrate and receptor

protein subunits, nature uses cluster carbohydrates in order

to obtain biologically meaningful aﬃnities for the receptors.

The cluster eﬀect appears when multivalent carbohydrates

interact with more than one receptor-binding site simulta-

neously and cooperatively, resulting in better cellular recog-

nition. Several methods of carbohydrate clustering have been

described, including the attachment of carbohydrates to

natural scaﬀolds, synthetic polymers, synthetic glycopeptides,

or simple oligomerization through organic linkers.^25,26Among

them, dendritic structures or glycodendrimers are emerging as

the ligand for carbohydrate-binding proteins.^27,28Due to rapid

advances in this area, promising potential medicinal applications

appeared during the past decade, including treatment of cancers

(renal cell carcinoma, melanoma, breast cancer, eradication of

metastasis).^29-32Recently, Ballardini et al. described the

synthesis and photophysical properties of two dendrimer

macrocycles, incorporating tetrasubstituted porphyrin units

as core and, in one case, four benzyloylated or deprotected

β-^D-glucopyranosyl and in an other case, twelve acetylated-

β-^D-glucopyranosyl or β-D-glucopyranosyl residues at the

peripheries of the tetrapyrrolic macrocycle.³³These unpro-

tected tetrasubstituted molecules are symmetric and highly

water-soluble but no in vitro photoeﬃciency was described.

In another approach, Matsuo et al. described the synthesis of

glycosylated myoglobin by a reconstitutional method as an

2011

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

Scheme 1. Synthesis of Glycodendrimeric Porphyrin 1

artiﬁcial prosthetic group inserted into sperm whale apomyo-

globin to aﬀord a β-galactosylated myoglobin.³⁴

Glycodendrimers 26-28 and 31-32 (Schemes 2 and 3) were

synthesized from di-tert-butyl 4-[2-(tert-butoxycarbonyl)ethyl]-

4-aminoheptane-dicarboxylate 20. This last compound was con-

densed with N-Z-glycine or N-Z-^L-phenylalanine by a modiﬁed

protocol described by Suda et al.,³⁹using HOAt/WSCI-HCl

as peptidic coupling agents, and giving quantitatively protected

compounds 21-Gly and 21-Phen. Deprotection of compounds

21 by a mixture of triﬂuoroacetic acid/methylene chloride

(1/2, v/v) gives compounds 22-Gly and 22-Phen with very

good yields (92% and 97%, respectively). Condensation of

peracetyl-glycosyl mono-, di-, or triethylene glycol amine^40-43

with dendrons 22-Gly and 22-Phen, in dry dimethylformamide,

in the presence of HATU and DIPEA as coupling agents, gives

Z-glycyl and Z-^L-phenylalanyl glycodendrimers 23-25 and 29-

30 in 31-84% and 32-90% yield ranges, respectively. Catalytic

reduction by H₂/Pd-C allows the cleavage of the benzyloxy-

carbonyl protecting group and the quantitative formation of

aminoglycodendrimers 26-28 and 31-32.

Analogous nonglycosylated dendron 37 (Scheme 4) was

prepared from diethylene glycol monochlorohydrin, which was

protected by an acetyl group (94% yield). Protected compound

33 was transformed to azide derivative 34 (95% yield) by NaN₃

in DMSO and was then reduced by H₂/Pd to amine 35 (88%

yield). This last one reacted with glycyl dendrons 22-Gly in the

presence of HATU and DIPEA in dry dimethylformamide to give

dendrimer 36 in 73% yield, which was deprotected by hydro-

genation to give dendrimer 37 (87%).

We had shown that an amphiphilic structure of the glycocon-

jugated photosensitizers induced a best photocytotoxicity in

vitro.¹³In the aim to increase this photoeﬃciency, we designed

two new families of glycoconjugated photosensitizers 1 and 2-

15 bearing only one glycodendrimer moiety, with variable length

for the spacer linking carbohydrate, various sugars, and two

diﬀerent amino acids (Figure 1). In two recent articles, we have

described the speciﬁc interactions of two glycodendrimeric

porphyrins with concanavalin A, a protein recognizing R-man-

nosyl groups.^35,36

’ RESULTS AND DISCUSSION

In this paper, we report the synthesis and characterization of

two families of glycodendrimeric meso-tetraarylporphyrins 1-15

(Figure 1). The ﬁrst one (compound 1) presents a relative steric

hindrance in the surrounding of glycoside moieties reducing the

mobility of sugars. In the second one (compounds 2-15), the

presence of -CH₂CH₂CONH-(CH₂CH₂O)-, -CH₂CH₂-

CONH-(CH₂CH₂O)₂-, or -CH₂CH₂CONH-(CH₂CH₂O)₃-

linkers between amino acid (glycyl or ^L-phenylalanyl) and glyco-

side parts reduces steric constraints between sugars and induces

some variable ﬂexibility of the sugars. The presence of an amino

acid could lead to a modiﬁcation of the hydrophobic part of the

photosensitizer, which could change its cellular penetration or its

anchorage in the lipid membrane of the targeted cancer cell.

Synthesis. Precursor 19 of the glycodendrimeric photosensi-

tizer 1, shown in Scheme 1, was prepared by the method

described by Polidori et al. in 23% total yield from N-Z-glycine.³⁷

Compound 19 was condensed by using a mixture of EDC-HOBt

as coupling agents in dry methylene chloride, with meso-5-(4-

benzoic acid)-10,15,20-triphenylporphyrin to give porphyrin 1-

OAc in 49% yield. Porphyrin 1 was obtained quantitatively by

Zemplen’s transesterification.³⁸

meso-5-(4-Benzoic acid)-10,15,20-triphenylporphyrin was con-

densed by using a mixture of EDC-HOBt as coupling agents in

dry methylene chloride, with amino glycodendrons 26-28, 31-

32, and 37 to give glycodendrimeric porphyrins 2-OAc-15-

OAc in the 40% yield range (Scheme 5). Deprotected glyco-

dendrimeric porphyrins 2-15 (Scheme 5) were obtained quan-

titatively by Zemplen’s transesteriﬁcation.³⁸

Characterization. H and ¹³C NMR spectroscopies, UV-

visible, fluorescence, elemental analysis, ESI, and MALDI-TOF

2012

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

Scheme 2. Preparation of Glycyl-Glycodendrimers

mass spectrometries characterized all precursor molecules and

final photosensitizers. The polarity of final deprotected porphyr-

ins was assessed by HPLC analysis.

the anomeric proton resonance of the glycosyl group appears

as a well-defined doublet with J = 8-9 Hz (character-

istic of a β anomeric configuration) for glucosyl and galactosyl

derivatives (1-OAc, 2-OAc, 2, 3-OAc, 3, 5-OAc, 5, 6-OAc, 6, 9-OAc,

9, 10-OAc, 10, 12-OAc, 12, 13-OAc, 13, 19, 23-β-GluOAc, 23-β-

GalOAc, 24-β-GluOAc, 24-β-GalOAc, 26-β-GluOAc, 26-β-Ga-

lOAc, 27-β-GluOAc, 27-β-GalOAc, 29-β-GluOAc, 29-β-GalOAc,

30-β-GluOAc, 30-β-GalOAc, 31-β-GluOAc, and 31-β-GalOAc)

and as a narrow doublet with J e 2 Hz or a singlet (R anomeric

configuration), for the mannosylated analogues (4-OAc, 4, 7-OAc,

7, 8-OAc, 8, 11-OAc, 11, 14-OAc, 14, 23-r-ManOAc, 24-r-

ManOAc, 25-r-ManOAc, 26-r-ManOAc, 27-r-ManOAc, 28-r-

ManOAc, 29-r-ManOAc, 30-r-ManOAc, and 31-r-ManOAc).

Mass Spectroscopy. Compounds 1-15 were characterized

by matrix-assisted laser desorption ionization-time-of-flight

(MALDI-TOF). For all glycodendrimeric porphyrins, one peak

was observed in the positive ion MALDI-TOF corresponding to

the protonated porphyrin macrocycle (MH^þ), with two small

additional peaks (MNa)^þand (MK)^þ.

Electronic Spectra. All protected glycodendrimeric por-

phyrins (1-OAc-15-OAc) were dissolved in methylene chlor-

ide and all free ones (1-15) in a mixture of methanol-

pyridine (24/1, v/v). Electronic spectra of all protected

compounds (1-OAc-15-OAc) are very similar to those of

known free base meso-5,10,15,20-tetraphenylporphyrin with a

Soret band near 420 nm and four less intense Q bands near

520, 550, 595, and 645 nm. The spectra of deprotected

compounds (1-15) presented a small blue shift due to the

¹H and ¹³C NMR. ¹H and ¹³C NMR (300 and 75.3 MHz),

homonuclear correlation (COSY), and heteronuclear multiple

coherence (HMQC) spectra were obtained for all precursor

dendrons and glycodendrimeric porphyrins in CDCl₃and

pyridine-d₅solutions. The NMR spectra of these molecules

are mainly governed by the symmetry of the tetrapyrrolic

macrocycle and by the nature of the sugar part. The overall

appearance of the H and ¹³C NMR spectra for protected

glycoconjugated macrocyclic compounds 1-OAc-14-OAc

was very similar to that for the p-glycoconjugated porphyrins

previously studied.^13,35For illustration, the H NMR spec-

trum of compound 2-OAc (Supportong information) is com-

posed of five main groups of resonance: the pyrrolic protons

appearing near 8.85 ppm as one singlet (6 H) and one doublet

(2 H), the phenyl protons as complex signals between 8.31

and 7.75 ppm, the sugar protons between 5.18 and 3.66 ppm,

and protective acetyl group protons between 2.16 and 1.97 ppm.

This results show that the ring current of the tetrapyrrolic

macrocycle does not affect the glycodendrimer moieties. The

absence of the deshielding effects is consistent with a con-

formation of compounds in which the dendrimers are located

in the same plan as the porphyrin ring. The NH pyrrolic

proton resonance appears as a broad singlet at -2.8 ppm. The

integrations were in agreement with the fixation of one

glycodendrimeric part bearing three sugar groups. Moreover,

2013

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

Scheme 3. Preparation of L-Phenylalanyl-Glycodendrimers

solvent, compared to their protected analogues, with a Soret

band near 414 nm and four less intense Q bands near 513, 546,

589, and 645 nm. As expected, the presence of the glycoden-

dron part on the meso-5-(4-benzoic acid)-10,15,20-triphe-

nylporphyrin does not alter the UV-visible spectra of the

chromophore systems. These spectral features show that the

glycodendrimeric porphyrins were monomeric in methylene

chloride and in a mixture of methanol-pyridine, at this con-

centration range.

Fluorescence Data. The corrected emission and excitation

fluorescence spectra of compounds 1-15 (Supporting In-

formation) in a mixture of MeOH/pyridine (24/1, v/v) are

very similar to those of known free base meso-5,10,15,20-

tetraphenylporphyrin with two emission bands at 650 and

715 nm but with a variable intensity ratio I_650/715nmbetween

0.80 and 1.46.

HPLC and Polarity. The polarity of the final porphyrins 1-

15 was checked by HPLC with a reverse phase column Waters

X Terra MS C18. In the first approximation, the retention time

(Rt) reflects the inverse of the polarity of the molecules.

Compounds 2-15 may be categorized by increasing reten-

tion time (Table 1), in three families: Rt between 13.51 and

13.74 min for compounds 2-8 for which the glycodendri-

meric group is linked to macrocycle by a glycine, 15.18 and

15.75 min for compounds 9-14 linked by a ^L-phenylalanine,

and 18.49 min for nonglycoconjugated dendrimer 15. These

results show that only the amino acid group, leading to a

modification of the hydrophobic part of the photosensitizer,

regulates the polarity of the system. On the other hand, the

partition coefficient (log P, Table 1) values of compounds 2-

14, obtained experimentally by the stir-flask method,⁴⁴are

near and included between -0.54 and -0.98 but do not

reflect retention time. A positive versus negative log P value

reflects preferential solubility in 2-octanol versus PBS solu-

tion, respectively. These values are characteristic of weakly

hydrophilic compounds for 2-14 and lipophilic for 15. The

nature of the monosaccharide β-glucose, β-galactose, and

R-mannose does not change noticeably the log P of the

compounds.

Cellular Phototoxicity. Phototoxicity of the photosensiti-

zers 1-15 was determined in HT 29 and Y79 cell lines by

cell survival fraction measurements after incubation during

24 h and exposure to >540 nm light with a fluence of 2 J/cm².

Toxicity in darkness was found to be negligible in all cases,

with a survival fraction close to 100% (>10 μM, 24 h incu-

bation). Photoefficiency of compounds 1-15 is presented

in Table 2.

Compounds 1 and 13 are not cytotoxic and phototoxic.

Among the results obtained with the glycodendrimer por-

phyrins, compounds 2, 4, and 6 have the highest LD₅₀(2.5

to 2.7 μM) for HT29 cells and compound 6 has an LD₅₀of

3 μM, being the best for Y79 cells. Compared with the value

2014

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

Scheme 4. Synthesis of Protected Diethyleneglycol Dendron

Scheme 5. Synthesis of Glycodendrimeric Porphyrins 2-15

of LD₅₀of TPP(p-DEG-O-R-ManOH)₃used as reference,¹³

porphyrins 2-14 are 6 times less phototoxic on HT29 and 10

times less phototoxic on Y79.

The analysis of the in vitro results obtained for both HT29 and

Y79 cell lines does not bring to light a link between the nature of

the sugar linked to the porphyrin and the type of membrane

2015

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

Table 1. Observed Retention Time (Rt) in HPLC Analysis on

Waters X Terra MS C18 5μm, 3.9 ꢀ 150 mm Column and

Log P_{2-octanol/PBS}Measured at 20°C

miscellaneous ﬂexible glycyl or ^L-phenylalanyl glycodendrons.

The asymmetric structure of these new glycoconjugated

porphyrins provides an amphiphilic character useful for drug

administration (hydrophilicity) and transport through the

organism. In spite of a speciﬁc aﬃnity of mannodendrimeric

photosensitizer 7 for lectin as Concanavalin A in a model of

cellular membrane of retinoblastoma cell being demonstrated

and the sugar groups of the glycoconjugated dendrimeric

porphyrins favoring their nonspeciﬁc interaction with mem-

branes,^35,36the measured in vitro phototoxicities of deriva-

tives 2-14 do not reﬂect these interactions.

compd

Rt (min)

log P ( 0.3

TPP

0.25

13.51

13.56

13.79

13.55

13.61

13.73

13.74

15.20

15.21

15.75

15.18

15.19

15.54

18.49

-0.54

-0.66

-0.76

-0.87

-0.65

-0.94

-0.73

-0.67

-0.62

-0.98

-0.91

-0.31

1.6

’ EXPERIMENTAL SECTION

Synthesis and physical characterization of compounds 21-Gly, 22-

Gly, 23-r-ManOAc, 24 r-ManOAc, 26-r-ManOAc, 27-r-ManOAc,

4-OAc, 7-OAc, 4, and 7 were described in ref 35.

5-{p-N-[Tris(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyloxy)

methyl]-N^r-glycinamidophenyl}-10,15,20-triphenylporphyrin,

1-OAc: meso-5-(4-Benzoic acid)-10,15,20-tetraphenylporphyrin (75 mg,

11.4 ꢀ 10^-2mmol), compound 19 (267 mg, 22.8 ꢀ 10^-2mmol), HOBt

(23 mg, 17.1 ꢀ 10^-2mmol), EDC (33 mg, 17.1 ꢀ 10^-2mmol), and Et₃N

(75 μL) were dissolved in dry methylene chloride (25 mL) under argon.

The solution was stirred at room temperature for 1 h. The reaction was

followed up by analytical thin layer chromatography (silica gel, methylene

chloride/acetone, 5/1, v/v). The crude mixture was washed with water,

diluted aqueous chlorhydric acid, water, aqueous sodium bicarbonate, and

water and dried over sodium sulfate then filtered and concentrated under

vacuum. Title compound 1-OAc was purified by preparative thin layer

chromatography (silica gel, methylene chloride/acetone, 4/1, v/v, R_f0.75).

Pure product was obtained by crystallization from a mixture of methyl-

ene chloride/heptane as a red powder (110 mg, yield 49%). Anal.

(C₉₃H₉₆N₆O₃₂), H₂O calcd: C 61.11, H 5.40, N 4.60. Found: C 61.22, H

Table 2. Dose of Porphyrin Derivatives (μM) Necessary To

Observe 50% of Cell Survival (LD50) after Incubation (24 h)

and Exposure to >540 nm Light at a Fluence of 2 J/cm²

LD₅₀((1) μM

compd

HT29

>10

Y79

>10

5.11, N 4.48. UV-vis spectrum in CH₂Cl₂:λ_max., nm(ε, L mmol^-1cm^-1

)

2.7

3.7

418 (423.6), 515 (18.2), 549.5 (9.7), 590 (7.7), 645 (6.4). H NMR

(CDCl₃): δ (ppm) 8.87 (d, 2H, J = 4.8 Hz, HC_2,8pyrrole), 8.85 (s, 4H,

HC_12,13,17,18pyrrole), 8.79 (d, 2H, J = 4.8 Hz, HC_3,7pyrrole), 8.32 (d, 4H,

J = 8.4 Hz, o-carboxyphenyl), 8.27 (d, 4H, J = 8.4 Hz, m-carboxyphenyl),

8.21 (d, 6H, J = 6.2 Hz, o-phenyl), 7.75 (m, 9H, m- and p-phenyl), 7.43

(t, 1H, J = 4.8 Hz, NHCH₂), 6.39 (s, 1H, NH-tris), 5.43 (d, 3H, J = 2.8 Hz,

HC₄), 5.20 (dd, 3H, J = 7.7 and 10.5 Hz, HC₂), 5.08 (dd, 3H, J = 3.4 and

10.5 Hz, HC₃), 4.50 (d, 3H, J = 7.7 Hz, HC₁), 4.38 (dd, 1H, J = 5.4 and

16.9 Hz, CH_2aglycine), 4.29 (m, 3H, H_aC₆), 4.24 (d, 3H, CH_2aNH), 4.22

(m, 1H, CH_2bglycine), 4.16 (m, 3H, H_bC₆), 3.99 (t, 3H, J = 6.6 Hz, HC₅),

3.88 (d, 3H, J = 10.2 Hz, CH_2b-NH), 2.19 (s, 9H, CH₃CO), 2.14 (s, 9H,

CH₃CO), 2.11 (s, 9H, CH₃CO), 2.0 (s, 9H, CH₃CO), -2.78 (s, 2H, NH).

¹³C NMR (CDCl₃): δ (ppm) 170.8 (COCH₃), 170.6 (COCH₃), 170.4

(COCH₃), 169.9 (COCH₃), 169.3 (glycine-CO), 167.8 (phenyl-CO),

146.2 (C₁carboxyphenyl), 142.4 (C₁, phenyl), 135 (o-carboxyphenyl),

134.9 (o-phenyl), 131.6 (C pyrrole), 128.1 (p-carboxyphenyl and p-phenyl),

127.1 (m-carboxyphenyl), 125.9 (m-phenyl), 120.9 (meso C₁₅), 120.7 (meso

C_10,20), 118.9 (meso C₅), 101.8 (C₁), 71.3 (C₅), 70.9 (C₃), 69.5 (C₂), 68.7

(CH₂-tris), 67.4 (C₄), 61.5 (C₆), 59.7 (C-NH), 43 (CH₂NH), 21.2

(CH₃CO), 21.1 (CH₃CO), 21 (CH₃CO), 20.9 (CH₃CO).

2.7

3.7

>10

2.5

5.6

5.2

4.5

3.7

5.2

>10

4.4

4.9

0.43¹⁴

5.8

0.35¹⁴

TPP-(p-Deg-O-r-ManOH)₃

receptor overexpressed in malignant cells although the carbohydrate-

lectin recognition has been demonstrated on a model of the cell

membrane.^35,36

Compound 21-Phen: N-Z-L-Phenylalanine (3.917 g, 13.1 mmol),

1-hydroxy-7-azabenzotriazole (HOAt, 1.774 g, 13.1 mmol), and WSCI-

HCl (2.519 g, 13.1 mmol) were dissolved in dry methylene chloride

(60 mL) and 20 (4.53 g, 10.9 mmol) in dry methylene chloride (2 mL)

was added. The reaction solution was stirred at room temperature for

36 h under argon. The reaction was quenched by addition of 10%

aqueous citric acid (25 mL). The aqueous layer was extracted with

methylene chloride. The organic layer was washed with water, saturated

aqueous sodium bicarbonate, and water, and then dried over sodium

sulfate, filtered, and concentrated under vacuum. The title compound

’ CONCLUSIONS

In this work, new glycodendrimeric porphyrins 1-15 bearing

three glycosyls linked on a dendrimeric motif have been de-

signed, synthesized, and characterized. We showed that it is

possible to prepare two types of glycodendrimer porphyrins with

an acceptable overall eﬃciency. In the ﬁrst family, the macro-

cyclic chromophore is linked with a constrained galactoden-

drimer and in the other one, the chromophore is linked with

2016

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

was obtained as a white powder (yield 99%) and used without purifica-

tion. MS calcd for C₃₉H₅₆N₂O₉(MNa^þ) 719.4, found 719.3. Anal.

(C₃₉H₅₆N₂O₉), H₂O calcd: C 65.52, H 8.18, N 3.92. Found: C 65.80, H

8.00, N 3.96. Melting point 94 °C. ¹H NMR (CDCl₃): δ (ppm) 7.34 (m,

5H, benzyloxycarbonyl), 7.22 (m, 5H, phenylalanine), 6.10 (broad t, 1H,

NH-C), 5.32 (d, 1H, NH phenylalanine), 5.09 (s, 2H, CH₂benzylo-

xycarbonyl), 4.28 (dd, 1H, HC phenylalanine), 3.03 (m, 2H, CH₂

phenylalanine), 2.05 [t, 6H, (CH₂)₃-C)], 1.84 (t, 6H, CH₂COO-t-Bu),

1.43 (s, 27H, CH₃t-Bu). ¹³C NMR (CDCl₃): δ (ppm) 172.7 (CO

dend), 169.9 (CO phenylalanine), 155.8 (CO benzyloxycarbonyl),

136.5 (C₁benzyloxycarbonyl), 136.2 (C₁phenylalanine), 129.3

(o-phenylalanine), 128.7 (p-phenylalanine), 128.5 (m-phenylalanine),

128.14 (o-benzyloxycarbonyl), 128.06 (p-benzyloxycarbonyl), 127 (m-

benzyloxycarbonyl), 80.6 [C-(CH₃)₃], 67 (CH₂benzyloxycarbonyl),

57.6 (C-NH), 56.6 (CH phenylalanine), 38.4 (CH₂phenylalanine),

29.9 (CH₂CO), 29.5 [(CH₂)₃-C], 28 (CH₃t-Bu).

Compound 22-Phen: 21-Phen (3.331 g, 4.78 mmol) was dis-

solved in methylene chloride (120 mL) and trifluoroacetic acid (60 mL)

and stirred 1 h at room temperature. The solution was concentrated

under vacuum. Crude product was diluted in methylene chloride, then

extracted with aqueous sodium hydroxide (5%). The aqueous phase was

washed with methylene chloride (twice) and acidified by chlorhydric

acid. The white precipitate was filtered, washed with water, and dried

under vacuum. Pure title compound was obtained as white crystals and

used without other purification (yield 97%). Melting point 171 °C

(pasty). MS calcd for C₂₇H₃₂N₂O₉(ES^þ) 529.1, found 529.1, and calcd

(ES^-) 527.2, found 527.1. Anal. (C₂₇H₃₂N₂O₉) calcd: C 61.35, H 6.10,

N 5.30. Found: C 61.75, H 6.34, N 5.28. ¹H NMR (MeOD-d₄): δ (ppm)

7.29 (m, 5H, benzyloxycarbonyl), 7.24 (m, 5H, phenylalanine), 5.04 (d,

2H, CH₂benzyloxycarbonyl), 4.29 (t, 1H, J = 7.6 Hz, HC phenyla-

lanine), 2.99 (dd, 1H, J = 7.4 and 13.5 Hz, CH_2aphenylalanine), 2.85

(dd, 1H, J = 7.9 and 13.4 Hz, CH_2bphenylalanine), 2.12 (m, 6H,

CH₂COO), 1.91 [m, 6H, (CH₂)₃-C)]. ¹³C NMR (MeOD-d₄): δ (ppm)

177.1 (COOH), 173.4 (CO phenylalanine), 158.2 (CO benzyloxy-

carbonyl), 138.4 (C₁benzyloxycarbonyl), 138.2 (C₁phenylalanine),

130.5 (o-phenylalanine), 129.6 (p-phenylalanine), 129.5 (m-phenylalanine),

129 (o-benzyloxycarbonyl), 128.9 (p-benzyloxycarbonyl), 127.9 (m-

benzyloxycarbonyl), 67.7 (CH₂benzyloxycarbonyl), 58.7 (C-NH),

58.4 (CH phenylalanine), 39 (CH₂phenylalanine), 30.6 [(CH₂)₃-C],

29.1 (CH₂COOH).

CH₃CO), 1.99 (m, 6H, CH₂CO). ¹³C NMR (CDCl₃): δ (ppm) 173.4

(CO dend), 170.7 (COCH₃), 170.1 (COCH₃), 169.6 (CO glycine),

169.5 (COCH₃), 169.3 (COCH₃), 156.9 (CO benzyloxycarbonyl),

136.3 (C₁benzyloxycarbonyl), 128.4 (o-benzyloxycarbonyl), 128 (p-

benzyloxycarbonyl), 127.8 (m-benzyloxycarbonyl), 100.7 (C₁), 72.5

(C₃), 71.7 (C₅), 71.1 (C₂), 68.4 (CH₂-O-glucosyl), 68.2 (C₄), 66.8

(CH₂benzyloxycarbonyl), 61.7 (C₆), 58 (C-NH), 44.7 (CH₂glycine),

39.2 (CH₂-NH), 30.7 (CH₂CO), 30.4 [(CH₂)₃-C], 20.6 (2CH₃CO),

20.45 (2CH₃CO).

Compound 23-β-GalOAc: The title compound was prepared as

23-β-GluOAc from 2-aminoethoxy-O-2⁰,3⁰,4⁰,6⁰-tetraacetyl-β-D-galac-

topyranose and 22-Gly. Pure title compound was obtained after crystal-

lization from a mixture of methylene chloride/ether as a beige powder

(yield 34%). MS calcd for C₆₈H₉₆N₅O₃₆(MH^þ) 1559.58, found

1559.10. Anal. (C₆₈H₉₅N₅O₃₆), 3H₂O calcd: C 50.65, H 6.31, N 4.34.

Found: C 50.8, H 6.15, N 4.45. ¹H NMR (CDCl₃): δ (ppm) 7.35 (m,

5H, benzyloxycarbonyl), 6.49 (broad t, 3H, CH₂-NH), 5.39 (d, 3H, J =

2.5 Hz, HC₄), 5.16 (dd, 3H, J = 7.9 and 10.4 Hz, HC₂), 5.13 (s, 2H, CH₂

benzyloxycarbonyl), 5.04 (dd, 3H, J = 3.2 and 10.4 Hz, HC₃), 4.48 (d,

3H, J = 7.8 Hz, HC₁), 4.14 (m, 6H, J = 6.4 Hz, HC₆), 3.95 (m, 3H, J =

6.4 Hz, HC₅), 3.84 (m, 3H, CH_2a-O-galactosyl), 3.75 (d, 2H, J = 5 Hz,

CH₂glycine), 3.67 (m, 3H, CH_2b-O-galactosyl), 3.40 (d, 6H, J = 4.9 Hz,

CH₂-NH), 2.16 [m, 6H, (CH₂)₃-C], 2.15 (s, 9H, CH₃CO), 2.13 (m,

6H, CH₂CO), 2.07 (s, 9H, CH₃CO), 2.05 (s, 9H, CH₃CO), 1.99 (s, 9H,

CH₃CO). ¹³C NMR (CDCl₃): δ (ppm) 173.1 (CO dend), 170.5

(COCH₃), 170.2 (COCH₃), 170.1 (COCH₃), 169.75 (COCH₃),

168.7 (CO glycine), 156.9 (CO benzyloxycarbonyl), 136.3 (C₁

benzyloxycarbonyl), 128.5 (o-benzyloxycarbonyl), 128.2 (p-benzyloxy-

carbonyl), 127.9 (m-benzyloxycarbonyl), 101.3 (C₁), 70.71 (C₅), 70.69

(C₃), 68.9 (C₂), 68.7 (CH₂-O-galactosyl), 67 (CH₂benzyloxycar-

bonyl), 66.95 (C₄), 61.3 (C₆), 58 (C-NH), 44.9 (CH₂glycine), 39.4

(CH₂-NH), 31 (CH₂CO), 30.7 [(CH₂)₃-C], 20.8 (CH₃CO), 20.7

(CH₃CO), 20.6 (CH₃CO), 20.55 (CH₃CO).

Compound 24-β-GluOAc: The title compond was prepared as

23-β-GluOAc from 2-aminoethoxyethoxy-O-2⁰,3⁰,4⁰,6⁰-tetraacetyl-β-D-

glucopyranose and 22-Gly. Pure title compound was obtained after

crystallization from a mixture of methylene chloride/diethyl ether as a

beige powder (yield 31%). MS calcd for C₇₄H₁₀₇N₅O₃₉Na (MNa^þ)

1712.65, found 1713.0. Anal. (C₇₄H₁₀₇N₅O₃₉), 4H₂O calcd: C 50.42, H

6.58, N 3.97. Found: C 50.31, H 6.17, N 4.04. H NMR (CDCl₃): δ

General Procedure for the Preparation of Compounds

23-25 and 29-30. All operations were identical with those de-

scribed for the synthesis of compound 23-β-GluOAc. A representative

example is described below.

(ppm) 7.33 (m, 5H, benzyloxycarbonyl), 6.46 (broad t, 3H, NH-CH₂),

5.75 (broad s, 1H, NH glycine), 5.24 (t, 3H, J = 9.4 Hz, HC₃), 5.13

(s, 2H, CH₂benzyloxycarbonyl), 5.09 (t, 3H, J = 9.4 Hz, HC₄), 4.99 (dd,

3H, J = 7.9 and 9.3 Hz, HC₂), 4.61 (d, 3H, J = 7.8 Hz, HC₁), 4.24 (dd,

3H, J = 4.4 and 12.3 Hz, H_aC₆), 4.11 (m, 3H, H_bC₆), 3.93 (m, 3H, CH_2a-

O-glucosyl), 3.78 (m, 2H, CH₂glycine), 3.70 (m, 6H, HC₅and CH_2b-O-

glucosyl), 3.60 (m, 6H, CH₂O), 3.49 (m, 6H, CH₂O), 3.4 (m, 3H, CH_2a-

NH), 3.33 (m, 3H, CH_2b-NH), 2.21 [m, 6H, (CH₂)₃-C], 2.08 (s, 9H,

CH₃CO), 2.05 (m, 6H, CH₂CO), 2.04 (s, 9H, CH₃CO), 2.02 (s, 9H,

CH₃CO), 2.00 (s, 9H, CH₃CO). ¹³C NMR (CDCl₃): δ (ppm) 173.2

(CO dend), 170.7 (COCH₃), 170.4 (COCH₃), 169.6 (COCH₃), 169.4

(COCH₃), 168.7 (CO glycine), 157 (CO benzyloxycarbonyl), 136.3

(C₁benzyloxycarbonyl), 128.5 (o-benzyloxycarbonyl), 128.1 (p-benzyl-

oxycarbonyl), 127.9 (m-benzyloxycarbonyl), 100.8 (C₁), 72.6 (C₃), 71.7

(C₅), 71.3 (C₂), 69.9 (CH₂O), 69.85 (CH₂O), 68.9 (CH₂-O-glucosyl),

68.4 (C₄), 66.9 (CH₂benzyloxycarbonyl), 61.9 (C₆), 58.2 (C-NH), 44.8

(CH₂glycine), 39.1 (CH₂-NH), 30.8 (CH₂CO), 30.6 [(CH₂)₃-C], 20.7

(2CH₃CO), 20.6 (2CH₃CO).

Compound 23-β-GluOAc: 22-Gly³⁵(0.100 g, 0.228 mmol)

and 2-aminoethoxy-O-2⁰,3⁰,4⁰,6⁰-tetraacetyl-β-D-glucopyranose (0.267 g,

0.684 mmol) were dissolved in dry free amine DMF (20 mL) under

argon. HATU (0.260 g, 0.684 mmol) and diisopropyl ethyl amine

(1 mL) were added. The solution was stirred overnight at room temper-

ature. Crude product was obtained after concentration under vacuum

and diluted in methylene chloride. The organic phase was washed

successively with water, aqueous HCl (10%), water, aqueous NaOH

(5%), and water then dried over sodium sulfate, filtered, and concen-

trated. Pure title compound was obtained after crystallization from a

mixture of methyl chloride/ether as yellow crystals and used without

other purification (0.185 g, 52% yield). Anal. (C₆₈H₉₅N₅O₃₆), 3H₂O

calcd: C 50.65, H 6.31, N 4.34. Found: C 50.35, H 6.22, N 4.52. ¹H NMR

(CDCl₃): δ (ppm) 7.35 (m, 5H, benzyloxycarbonyl), 6.73 (broad t, 3H,

NH-CH₂), 5.21 (t, 3H, J = 9.4 Hz, HC₃), 5.11 (s, 2H, CH₂

benzyloxycarbonyl), 5.07 (t, 3H, J = 9.5 Hz, HC₄), 4.96 (t, 3H, HC₂),

4.53 (d, 3H, J = 7.9 Hz, HC₁), 4.25 (dd, 3H, J = 4.4 and 12.2 Hz, H_aC₆),

4.15 (m, 3H, H_bC₆), 3.74 (m, 11H, CH₂-O-glucosyl, CH₂glycine and

HC₅), 3.41 (m, 6H, CH₂-NH), 2.17 [m, 6H, (CH₂)₃-C], 2.08 (s, 9H,

CH₃CO), 2.03 (s, 9H, CH₃CO), 2.02 (s, 9H, CH₃CO), 1.99 (s, 9H,

Compound 24-β-GalOAc: The title compound was prepared

as 23-β-GluOAc from 2-aminoethoxyethoxy-O-2⁰,3⁰,4⁰,6⁰-tetraacetyl-

β-^D-galactopyranose and 22-Gly. Pure title compound was obtained

after crystallization from a mixture of methylene chloride/diethyl ether

as a beige powder (yield 47%). MS calcd for C₇₄H₁₀₈N₅O₃₉(MH^þ)

1690.65 and (MNa^þ) 1712.65, found 1690.9 and 1712.8. Anal.

2017

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

(C₇₄H₁₀₇N₅O₃₉), 3H₂O calcd: C 50.94, H 6.51, N 4.01. Found: 50.78,

H 6.28, N 4.42. ¹H NMR (CDCl₃): δ (ppm) 7.33 (m, 5H,

benzyloxycarbonyl), 6.46 (broad t, 3H, CH₂-NH), 5.72 (broad s, 1H,

NH-C), 5.39 (dd, 3H, J = 3.3 Hz, HC₄), 5.19 (dd, 3H, J = 7.8 and 10.4

Hz, HC₂), 5.13 (s, 2H, CH₂benzyloxycarbonyl), 5.06 (dd, 3H, J = 3.3

and 10.4 Hz, HC₃), 4.58 (d, 3H, J = 7.8 Hz, HC₁), 4.14 (m, 6H, HC₆),

3.94 (m, 6H, HC₅and CH_2a-O-galactosyl), 3.79 (m, 2H, CH₂glycine),

3.71 (m, 3H, CH_2b-O-galactosyl), 3.60 (m, 6H, CH₂O), 3.50 (m, 6H,

CH₂O), 3.42 (m, 3H, CH_2a-NH), 3.33 (m, 3H, CH_2b-NH), 2.22 [m,

6H, (CH₂)₃-C], 2.15 (s, 9H, CH₃CO), 2.06 (m, 6H, CH₂CO), 2.06 (s,

9H, CH₃CO), 2.04 (s, 9H, CH₃CO), 1.99 (s, 9H, CH₃CO). ¹³C NMR

(CDCl₃): δ (ppm) 173.1 (CO dend), 170.4 (COCH₃), 170.2 (2

COCH₃), 169.8 (COCH₃), 168.6 (CO glycine), 157 (CO benzyloxy-

carbonyl), 136.2 (C₁benzyloxycarbonyl), 128.5 (o-benzyloxycarbonyl),

128.2 (p-benzyloxycarbonyl), 127.9 (m-benzyloxycarbonyl), 101.3 (C₁),

70.8 (C₃), 70.6 (C₅), 70 (CH₂O), 69.8 (CH₂O), 68.92 (CH₂-O-galac-

tosyl), 68.88 (C₂), 66.9 (C₄), 66.8 (CH₂benzyloxycarbonyl), 61.2 (C₆),

58.2 (C-NH), 44.8 (CH₂glycine), 39.3 (CH₂-NH), 30.9 (CH₂CO),

30.7 [(CH₂)₃-C], 20.8 (CH₃CO), 20.7 (CH₃CO), 20.65 (CH₃CO),

20.6 (CH₃CO).

Compound 26-β-GalOAc: The title compound was prepared as

26-β-GluOAc from 23-β-GalOAc. Pure title compound was obtained

after crystallization from a mixture of methylene chloride/diethyl ether

as yellow crystals (yield 70%). MS calcd for C₆₀H₉₀N₅O₃₄(MH^þ)

1424.54, found 1424.90. Anal. (C₆₀H₈₉N₅O₃₄), 4H₂O calcd: C 48.16, H

6.53, N 4.68. Found: C 48.16, H 6.08, N 4.90. H NMR (CDCl₃): δ

(ppm) 5.39 (d, 3H, J = 2.7 Hz, HC₄), 5.15 (m, 3H, J = 7.7 Hz, HC₂), 5.05

(m, 3H, J = 10.4 Hz, HC₃), 4.52 (d, 3H, J = 7.7 Hz, HC₁), 4.15 (m, 6H,

HC₆), 3.97 (m, 3H, HC₅), 3.96 (m, 2H, CH₂glycine), 3.85 (m, 3H,

CH_2a-O-galactosyl), 3.68 (m, 3H, CH_2b-O-galactosyl), 3.40 (d, 6H,

CH₂-NH), 2.17 (s, 9H, CH₃CO), 2.16 [m, 6H, (CH₂)₃-C], 2.08 (s, 9H,

CH₃CO), 2.05 (s, 9H, CH₃CO), 2.00 (m, 6H, CH₂CO), 1.99 (s, 9H,

CH₃CO). ¹³C NMR (CDCl₃): δ (ppm) 170.5 (COCH₃), 170.2

(COCH₃), 170 (COCH₃), 169.8 (COCH₃), 168.6 (CO glycine),

101.2 (C₁), 70.7 (C₃and C₅), 68.8 (C₂), 68.5 (CH₂-O-galactosyl), 67

(C₄), 61.2 (C₆), 57.7 (C-NH), 45 (CH₂glycine), 39.4 (CH₂-NH), 30.9

(CH₂CO), 30.5 [(CH₂)₃-C], 20.8 (CH₃CO), 20.7 (CH₃CO), 20.6

(CH₃CO), 20.5 (CH₃CO).

Compound 27-β-GluOAc: The title compound was prepared as

26-β-GluOAc from 24-β-GluOAc. Pure title compound was obtained

after crystallization from a mixture of methylene chloride/diethyl ether

as colorless crystals (yield 82%). MS calcd for C₆₆H₁₀₂N₅O₃₇(MH^þ)

1556.62 and (MNa^þ) 1578.62, found 1556.8 and 1578.8. Anal.

(C₆₆H₁₀₁N₅O₃₇), 10H₂O calcd: C 45.63, H 6.97, N 4.32. Found: C

45.99, H 6.29, N 4.37. ¹H NMR (CDCl₃): δ (ppm) 5.23 (t, 3H, J = 9.6

Hz, HC₃), 5.09 (t, 3H, J = 9.4 Hz, HC₄), 4.99 (t, 3H, HC₂), 4.61 (d, 3H, J

= 7.8 Hz, HC₁), 4.27 (dd, 3H, J = 4.4 and 12.3 Hz, H_aC₆), 4.14 (m, 3H,

H_bC₆), 3.96 (m, 3H, CH_2a-O-glucosyl), 3.72 (m, 3H, HC₅), 3.67 (m,

3H, CH_2b-O-glucosyl), 3.61 (m, 6H, CH₂O), 3.51 (m, 6H, CH₂O), 3.38

(m, 6H, CH₂-NH), 2.19 [m, 6H, (CH₂)₃-C], 2.09 (s, 9H, CH₃CO),

2.06 (m, 6H, CH₂CO), 2.05 (s, 9H, CH₃CO), 2.03 (s, 9H, CH₃CO),

2.01 (s, 9H, CH₃CO). ¹³C NMR (CDCl₃): δ (ppm) 173.2 (CO dend),

170.6 (COCH₃), 170.2 (COCH₃), 169.5 (COCH₃), 169.4 (COCH₃),

100.7 (C₁), 72.6 (C₃), 71.7 (C₅), 71.2 (C₂), 69.7 (2 CH₂O), 68.9 (CH₂-

O-glucosyl), 68.3 (C₄), 61.8 (C₆), 57.8 (C-NH), 39.1 (CH₂-NH), 30.8

(CH₂-CO), 30.5 [(CH₂)₃-C], 20.6 (2 CH₃CO), 20.5 (2 CH₃CO).

Compound 27-β-GalOAc: The title compound was prepared as

26-β-GluOAc from 24-β-GalOAc. Pure title compound was obtained

after crystallization from a mixture of methylene chloride/diethyl ether

as a beige powder (yield 79%). MS calcd for C₆₆H₁₀₂N₅O₃₇(MH^þ)

1556.62, found 1556.9. Anal. (C₆₆H₁₀₁N₅O₃₇), 6H₂O calcd: C 47.58, H

Compound 25-r-ManOAc: The title compound was prepared as

23-β-GluOAc from 2-aminoethoxyethoxyethoxy-O-2⁰,3⁰,4⁰,6⁰-tetraace-

tyl-R-^D-mannopyranose and 22-Gly. Pure title compound was obtained

as paste and used without other purification (yield 84%). Anal.

(C₈₀H₁₁₉N₅O₄₂), H₂O calcd: C 52.20, H 6.63, N 3.80. Found: C 51.95,

H 6.85, N 4.03. H NMR (CDCl₃): δ (ppm) 7.35 (m, 5H, benzyl-

oxycarbonyl), 6.67 (broad t, 3H, NH), 6.25 (broad s, 1H, NH), 5.85

(broad t, 1H, J = 5.5 Hz, NH glycine), 5.30 (m, 6H, CH₂), 5.27 (m, 12H,

CH₂), 4.88 (s, 3H, HC₁), 4.28 (dd, 3H, J = 4.6 and 12 Hz, H _aC₆), 4.10

(d, 3H, J = 12 Hz, H_bC₆), 4.07 (m, 3H, HC₅), 3.81 (m, 6H, CH₂), 3.75

(d, 2H, CH₂glycine), 3.68 (m, 6H, CH₂), 3.65 (m, 24H, CH₂), 3.41 (m,

6H, CH₂), 2.20 (m, 12H, CH₂), 2.15 (s, 9H, CH₃CO), 2.10 (s, 9H,

CH₃CO), 2.04 (s, 9H, CH₃CO), 2 (m, 12H, CH₂), 1.99 (s, 9H,

CH₃CO). ¹³C NMR (CDCl₃): δ (ppm) 173.6 (CO dend), 171.1

(COCH₃), 170.5 (COCH₃), 170.4 (COCH₃), 170.1 (COCH₃), 169.1

(CO glycine), 157.1 (CO), 136.8 (C₁benzyloxycarbonyl), 128.9

(o-benzyloxycarbonyl), 128.5 (p-benzyloxycarbonyl), 128.4 (m-benzyloxy-

carbonyl), 98.1 (C₁), 71 (CH₂), 70.6 (CH₂), 70.3 (CH₂), 70.2 (CH₂),

69.5 (C_2,3,4), 68.8 (C₅), 67.7 (CH₂), 67.4 (CH₂benzyloxycarbonyl),

66.5 (C_2,3,4), 62.8 (C₆), 58.7 (C-NH), 45.4 (CH₂glycine), 39.7 (CH₂),

31.5 (CH₂), 31.1 (CH₂), 21.31 [(CH₂)₃-C], 21.27 [(CH₂)₃-C], 21.1

[(CH₂)₃C].

6.59, N 4.62. Found: C 47.79, H 6.21, N 4.32. H NMR (CDCl₃): δ

General Procedure for the Preparation of Compounds

26-28-r-ManOAc and 31-32. All operations were identical with

those described for the synthesis of compound 26-β-GluOAc. A

representative example is described below.

(ppm) 6.88 (broad s, 1H, NH-C), 5.39 (d, 3H, J = 2.8 Hz, HC₄), 5.18

(m, 3H, HC₂), 5.05 (dd, 3H, J = 2.8 and 10.2 Hz, HC₃), 4.57 (d, 3H, J =

7.7 Hz, HC₁), 4.14 (m, 6H, HC₆), 3.96 (m, 6H, HC₅and CH_2b-O-

galactosyl), 3.96 (m, 2H, CH₂glycine), 3.71 (m, 3H, CH_2a-O-

galactosyl), 3.61 (m, 6H, CH₂O), 3.5 (m, 6H, CH₂O), 3.38 (m, 6H,

CH₂-NH), 2.23 [m, 6H, (CH₂)₃-C], 2.15 (s, 9H, CH₃CO), 2.06 (s, 9H,

CH₃CO), 2.05 (s, 9H, CH₃CO), 2.05 (m, 6H, CH₂CO), 1.99 (s, 9H,

CH₃CO). ¹³C NMR (CDCl₃): δ (ppm) 173.1 (CO dend), 170.4

(COCH₃), 170.2 (COCH₃), 170.1 (COCH₃), 169.7 (COCH₃), 168.5

(CO glycine), 101.3 (C₁), 70.74 (C₃), 70.68 (C₅), 69.8 (2CH₂O), 68.9

(CH₂-O-galactosyl), 68.85 (C₂), 67 (C₄), 61.2 (C₆), 57.9 (C-NH), 45

(CH₂glycine), 39.1 (CH₂-NH), 30.7 (CH₂CO), 30.5 [(CH₂)₃-C], 20.8

(CH₃CO), 20.7 (2CH₃CO), 20.6 (CH₃CO).

Compound 26-β-GluOAc: 23-β-GluOAc (0.5 g, 1 equiv, 0.32

mmol) and palladium on activated carbon (Pd/C 10%, 270 mg) were

dissolved in methanol (200 mL). The solution was stirred under

hydrogen atmosphere (3 bar) at room temperature for 24 h. The

suspension was filtered over Celite and concentrated under vacuum.

Pure title compound was obtained as beige crystals and used without

purification (yield 85%). MS calcd for C₆₀H₉₀N₅O₃₄(MH^þ) 1424.54,

found 1424.30. H NMR (CDCl₃): δ (ppm) 5.21 (t, 3H, J = 9.4 Hz,

HC₃), 5.08 (t, 3H, J = 9.4 Hz, HC₄), 4.97 (m, 3H, HC₂), 4.54 (m, 3H,

HC₁), 4.25 (m, 3H, H_aC₆), 4.16 (m, 3H, H_bC₆), 3.71 (m, 9H, HC₅and

CH₂-O-glucosyl), 3.38 (m, 6H, CH₂-NH), 2.20 [m, 6H, (CH₂)₃-C],

2.09 (s, 9H, CH₃CO), 2.06 (s, 9H, CH₃CO), 2.04 (m, 6H, CH₂CO),

2.03 (s, 9H, CH₃CO), 2.01 (s, 9H, CH₃CO). ¹³C NMR (CDCl₃): δ

(ppm) 173.7 (CO dend), 170.7 (COCH₃), 170.2 (COCH₃), 169.7

(COCH₃), 169.4 (COCH₃), 100.7 (C₁), 72.6 (C₃), 71.8 (C₅), 71.3

(C₂), 68.9 (CH₂-O-glucosyl), 68.3 (C₄), 61.9 (C₆), 58.4 (C-NH), 42.3

(CH₂glycine), 39.3 (CH₂-NH), 30.6 [CH₂CO and (CH₂)₃-C], 20.7

(2CH₃CO), 20.6 (2CH₃CO).

Compound 28-r-ManOAc: The title compound was prepared as

26-β-GluOAc from 25-r-ManOAc. Pure title compound was obtained

after drying under vacuum as a brown powder and used without other

purification (yield 94%). Anal. not obtained. H NMR (CDCl₃): δ

(ppm) 5.29 (m, 9H, HC_2,3,4), 4.86 (s, 3H, HC₁), 4.26 (m, 3H), 4.10 (m,

6H, HC₅and H_bC₆), 3.68 (m, 8H, CH₂-O-mannosyl and CH₂), 3.46

(m, 6H), 2.33 (m, 6H, CH₂), 2.16 (s, 9H, CH₃CO), 2.09 (s, 9H,

CH₃CO), 2.05 (s, 9H, CH₃CO), 2.00 (m, 11H, CH₂and CH₃CO).

¹³C NMR (CDCl₃): δ (ppm) 171.7 (COCH₃), 171.3 (COCH₃), 171.2

2018

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

(COCH₃), 171 (COCH₃), 170.7 (COCH₃), 166.2 (CO glycine), 142.8

(C-SO₃H), 141.2 (p-phenyl), 129.8 (m-phenyl), 126.7 (o-phenyl), 98.5

(C₁), 71.5 (C_2,3,4), 71.3 (C_2,3,4), 70.8 (C_2,3,4), 68.1 (C₅), 66.9 (C-O-

mannosyl), 63.3 (C6), 43.6 (CH₂-glycine), 40.9 (C-NH), 22.2 (CH₃-

phenyl), 21.8 (CH₃), 21.6 (CH₃).

C₇₅H₁₀₁N₅O₃₆Na (MNa^þ) 1670.62, found 1670.7. Anal. (C₇₅H₁₀₁

N₅O₃₆), 3H₂O calcd: C 52.91, H 6.33, N 4.11. Found: C 53.15; H 6.19;

N 4.33. ¹H NMR (CDCl₃): δ (ppm) 7.32 (m, 5H, benzyloxycarbonyl),

7.24 (m, 5H, phenylalanine), 6.65 (broad t, 3H, CH₂-NH), 5.37 (dd,

3H, J = 3.2 and 10 Hz, HC₃), 5.30 (m, 3H, HC₂), 5.27 (m, 3H, HC₄),

5.07 (s, 2H, CH₂benzyloxycarbonyl), 4.83 (d, 3H, J = 1.1 Hz, HC₁),

4.31 (m, 1H, HC phenylalanine), 4.28 (dd, 3H, J = 5.7 and 12.3 Hz,

H_aC₆), 4.14 (dd, 3H, J = 2.0 and 12.2 Hz, H_bC₆), 4.03 (m, 3H, HC₅),

3.75 (m, 3H, CH_2a-O-mannosyl), 3.51 (m, 6H, CH₂NH), 3.34 (m, 3H,

CH_2b-O-mannosyl), 3.03 (dd, 1H, J = 7 Hz, CH_2a-phenylalanine), 2.96

(m, 1H, J = 6.8 Hz, CH_2b-phenylalanine), 2.17 [m, 6H, (CH₂)₃-C], 2.15

(s, 9H, CH₃CO), 2.10 (s, 9H, CH₃CO), 2.05 (m, 6H, CH₂CO), 2.03 (s,

9H, CH₃CO), 1.97 (s, 9H, CH₃CO). ¹³C NMR (CDCl₃): δ (ppm)

173.5 (CO dend), 170.9 (CO phenylalanine), 170.7 (COCH₃), 170.2

(COCH₃), 170.1 (COCH₃), 169.7 (COCH₃), 156.2 (CO benzyloxy-

carbonyl), 136.7 (C₁benzyloxycarbonyl), 136.3 (C₁phenylalanine),

129.3 (o-phenylalanine), 128.5 (p-phenylalanine), 128.5 (m-phenylal-

anine), 128.1 (o-benzyloxycarbonyl), 127.8 (p-benzyloxycarbonyl),

126.9 (m-benzyloxycarbonyl), 97.6 (C₁), 69.4 (C₃), 69.1 (C₂), 68.6

(C₅), 67.1 (CH₂benzyloxyarbonyl), 66.8 (CH₂-O-mannosyl), 66 (C₄),

62.4 (C₆), 58.5 (C-NH), 57 (CH phenylalanine), 38.8 (CH₂-NH),

38 (CH₂phenylalanine), 31.2 (CH₂CO), 30.6 [(CH₂)₃-C], 20.8

(2 CH₃CO), 20.7 (2 CH₃CO).

Compound 29-β-GluOAc: The title compound was prepared as

23-β-GluOAc from 22-Phen and 2-aminoethoxy-O-2⁰,3⁰,4⁰,6⁰-tetraace-

tyl-β-^D-glucopyranose tosylate. Pure title compound was obtained after

crystallization from a mixture of methylene chloride/diethyl ether as a

yellow orange powder (yield 90%). MS calcd for C₇₅H₁₀₁N₅O₃₆Na

(MNa^þ) 1670.62, found 1670.7. Anal. (C₇₅H₁₀₁N₅O₃₆), 4H₂O calcd: C

52.35, H 6.39, N 4.07. Found: C 52.18, H 6.01, N 4.09. H NMR

(CDCl₃): δ (ppm) 7.33 (m, 5H, benzyloxycarbonyl), 7.25 (m, 5H,

phenylalanine), 6.37 (broad t, 3H, CH₂-NH), 5.18 (dd, 3H, J = 9.5 Hz,

HC₃), 5.08 (d, 3H, HC₄), 5.07 (s, 2H, CH₂benzyloxycarbonyl), 4.99

(dd, 3H, J = 9.3 Hz, HC₂), 4.51 (d, 3H, J = 7.8 Hz, HC₁), 4.31 (m, 1H,

HC phenylalanine), 4.25 (dd, 3H, J = 4.5 and 12.2 Hz, H_aC₆), 4.14 (dd,

3H, J = 2.0 and 12.3 Hz, H_bC₆), 3.82 (m, 3H, CH_2a-O-glucosyl), 3.70

(m, 3H, HC₅), 3.69 (m, 3H, CH_2b-O-glucosyl), 3.37 (d, 6H, J = 5.2 Hz,

CH₂-NH), 3.06 (m, 1H, CH_2a-phenylalanine), 2.95 (m, 1H, CH_2b-

phenylalanine), 2.15 [m, 6H, (CH₂)₃-C], 2.07 (s, 9H, CH₃CO), 2.05 (s,

9H, CH₃CO), 2.02 (s, 9H, CH₃CO), 2.00 (s, 9H, CH₃CO), 1.98 (m,

6H, CH₂CO). ¹³C NMR (CDCl₃): δ (ppm) 173 (CO dend), 170.7

(COCH₃), 170.5 (CO phenylalanine), 170.1 (COCH₃), 169.5

(COCH₃), 169.4 (COCH₃), 155.9 (CO benzyloxycarbonyl), 136.6

(C₁benzyloxycarbonyl), 136.3 (C₁phenylalanine), 129.4 (o-phenyl-

alanine), 128.6 (p-phenylalanine), 128.5 (m-phenylalanine), 128.1

(o-benzyloxycarbonyl), 127.9 (p-benzyloxycarbonyl), 126.9 (m-benzyl-

oxycarbonyl), 100.8 (C₁), 72.6 (C₃), 71.8 (C₅), 71.2 (C₂), 68.8 (CH₂-

O-glucosyl), 68.3 (C₄), 66.8 (CH₂benzyloxycarbonyl), 61.8 (C₆), 58.1

(C-NH), 57 (CH phenylalanine), 39.3 (CH₂-NH), 38.3 (CH₂phenyl-

alanine), 30.7 (CH₂CO), 30.4 [(CH₂)₃-C]), 20.7 (2 CH₃CO), 20.6

(2 CH₃CO).

Compound 29-β-GalOAc: The title compound was prepared as

23-β-GluOAc from 22-Phen and 2-aminoethoxy-O-2⁰,3⁰,4⁰,6⁰-tetraace-

tyl-β-^D-galactopyranose. Pure title compound was obtained after crystal-

lization from a mixture of methylene chloride/diethyl ether as a beige

powder (yield 46%). MS calcd for C₇₅H₁₀₁N₅O₃₆Na (MNa^þ) 1670.62,

found 1670.7. Anal. (C₇₅H₁₀₁N₅O₃₆), 5H₂O calcd: C 51.81, H 6.43, N

4.03. Found: C 51.80; H 6.04; N 4.58. ¹H NMR (CDCl₃): δ (ppm) 7.33

(m, 5H, benzyloxycarbonyl), 7.24 (m, 5H, phenylalanine), 6.23 (broad t,

3H, CH₂-NH), 5.39 (d, 3H, J = 2.8 Hz, HC₄), 5.19 (dd, 3H, J = 7.8 and

10.3 Hz, HC₂), 5.09 (s, 2H, CH₂benzyloxycarbonyl), 5.04 (dd, 3H, J =

3.3 and 10.4 Hz, HC₃), 4.51 (d, 3H, J = 7.8 Hz, HC₁), 4.30 (m, 1H, HC

phenylalanine), 4.16 (m, 6H, HC₆), 3.94 (m, 3H, HC₅), 3.83 (m, 3H,

CH_2a-O-galactosyl), 3.67 (m, 3H, CH_2b-O-galactosyl), 3.39 (d, 6H, J =

5.6 Hz, CH₂-NH), 3.00 (s, 2H, CH₂-phenylalanine), 2.16 [m, 6H,

(CH₂)₃-C], 2.12 (s, 9H, CH₃CO), 2.06 (s, 9H, CH₃CO), 2.04 (s, 9H,

CH₃CO), 1.99 (s, 9H, CH₃CO), 1.99 (m, 6H, CH₂CO). ¹³C NMR

(CDCl₃): δ (ppm) 173 (CO dend), 170.5 (CO phenylalanine), 170.4

(COCH₃), 170.1 (COCH₃), 170 (COCH₃), 169.7 (COCH₃), 156.4

(CO benzyloxycarbonyl), 136.6 (C₁benzyloxycarbonyl), 136.3 (C₁

phenylalanine), 129.4 (o-phenylalanine), 128.6 (p-phenylalanine),

128.5 (m-phenylalanine), 128,1 (o-benzyloxycarbonyl), 127.8 (p-ben-

zyloxycarbonyl), 127 (m-benzyloxycarbonyl), 101.3 (C₁), 70.7 (C₅and

C₃), 68.8 (C₂), 68.7 (CH₂-O-galactosyl), 67 (C₄), 66.8 (CH₂

benzyloxycarbonyl), 61.3 (C₆), 58 (C-NH), 57 (CH phenylalanine),

39.3 (CH₂-NH), 38.2 (CH₂phenylalanine), 30.7 (CH₂CO), 30.4

[(CH₂)₃-C], 20.8 (CH₃CO), 20.6 (CH₃CO), 20.6 (CH₃CO), 20.5

(CH₃CO).

Compound 30-β-GluOAc: The title compound was prepared as

23-β-GluOAc from 22-Phen and 2-aminoethoxyethoxy-O-2⁰,3⁰,4⁰,6⁰-

tetraacetyl-β-^D-glucopyranose. Pure title compound was obtained after

crystallization from a mixture of methylene chloride/diethyl ether as

beige crystals (yield 32%). MS calcd for C₈₁H₁₁₃N₅O₃₉Na (MNa^þ)

1802.7, found 1802.8. Anal. (C₈₁H₁₁₃N₅O₃₉), 3H₂O calcd: C 53.03, H

6.54, N 3.82. Found: C 52.87, H 6.32, N 4.18. H NMR (CDCl₃): δ

(ppm) 7.33 (m, 5H, benzyloxycarbonyl), 7.25 (m, 5H, phenylalanine),

6.35 (broad t, 3H, CH₂-NH), 5.54 (m, 1H, NH-C), 5.48 (m, 1H, NH

phenylalanine), 5.26 (t, 3H, J = 9.5 Hz, HC₃), 5.09 (m, 5H, HC₄and

CH₂benzyloxycarbonyl), 5.0 (dd, 3H, J = 7.9 and 9.5 Hz, HC₂), 4.62 (d,

3H, J = 7.9 Hz, HC₁), 4.34 (m, 1H, HC phenylalanine), 4.24 (dd, 3H, J =

4.5 and 12.3 Hz, H_aC₆), 4.11 (m, 3H, H_bC₆), 3.94 (m, 3H, CH_2a-O-

glucosyl), 3.70 (m, 6H, CH_2b-O-glucosyl and HC₅), 3.61 (m, 6H,

CH₂O), 3.49 (m, 6H, CH₂O), 3.4 (m, 3H, CH_2a-NH), 3.3 (m, 3H,

CH_2b-NH), 3.02 (m, 2H, CH₂-phenylalanine), 2.07 (s, 9H, CH₃CO),

2.06 (m, 6H, [(CH₂)₃-C]), 2.04 (s, 9H, CH₃CO), 2.02 (s, 9H,

CH₃CO), 2.01 (s, 9H, CH₃CO), 1.91 (m, 6H, CH₂CO). ¹³C NMR

(CDCl₃): δ (ppm) 173.1 (CO dend), 170.7 (COCH₃), 170.4 (CO

phenylalanine), 169.5 (2COCH₃), 169.4 (COCH₃), 156 (CO benzyl-

oxycarbonyl), 136.5 (C₁phenylalanine), 136.2 (C₁benzyloxycarbonyl),

129.3 (o-phenylalanine), 128.7 (p-phenylalanine), 128.6 (m-phenyl-

alanine), 128.2 (o-benzyloxycarbonyl), 127.7 (p-benzyloxycarbonyl),

127 (m-benzyloxycarbonyl), 100.8 (C₁), 72.6 (C₃), 71.7 (C₅), 71.2

(C₂), 70.1 (CH₂O), 69.9 (CH₂O), 68.9 (CH₂-O-glucosyl), 68.4 (C₄),

66.8 (CH₂benzyloxycarbonyl), 61.9 (C₆), 58.1 (C-NH), 56.8 (CH

phenylalanine), 39.2 (CH₂-NH), 38.2 (CH₂phenylalanine), 30.6

(CH₂CO), 30.5 [(CH₂)₃-C], 20.7 (2 CH₃CO), 20.6 (2 CH₃CO).

Compound 30-β-GalOAc: The title compound was prepared as

23-β-GluOAc from 22-Phen and 2-aminoethoxyethoxy-O-2⁰,3⁰,4⁰,6⁰-

tetraacetyl-β-^D-galactopyranose. Pure title compound was obtained after

crystallization from a mixture of methylene chloride/diethyl ether as an

orange powder (yield 61%). MS calcd for C₈₁H₁₁₃N₅O₃₉Na (MNa^þ)

1802.7, found 1802.8. Anal. (C₈₁H₁₁₃N₅O₃₉), 2H₂O calcd: C 53.55, H

6.49, N 3.85. Found: C 53.77, H 6.34, N 4.25. H NMR (CDCl₃): δ

(ppm) 7.33 (m, 5H, benzyloxycarbonyl), 7.25 (m, 5H, phenylalanine),

6.44 (broad t, 3H, CH₂-NH), 5.50 (m, 3H, NH phenylalanine), 5.38 (d,

3H, J = 3.0 Hz, HC₄), 5.21 (dd, 3H, J = 7.8 and 10.4 Hz, HC₂), 5.09 (m,

5H, CH₂benzyloxycarbonyl and HC₃), 4.64 (d, 3H, J = 7.8 Hz, HC₁),

4.36 (m, 1H, HC phenylalanine), 4.11 (m, 6H, HC₆), 3.94 (m, 6H, HC₅

and CH_2a-O-galactosyl), 3.74 (m, 3H, CH_2b-O-galactosyl), 3.61 (m, 6H,

Compound 29-r-ManOAc: The title compound was prepared as

23-β-GluOAc from 22-Phen and 2-aminoethoxy-O-2⁰,3⁰,4⁰,6⁰-tetraace-

tyl-R-^D-mannopyranose. Pure title compound was obtained as a yellow

powder and used without purification (yield 90%). MS calcd for

2019

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

CH₂O), 3.48 (m, 9H, CH₂O and CH_2a-NH), 3.26 (m, 3H, CH_2b-NH),

3.03 (m, 2H, CH₂-phenylalanine), 2.14 (s, 9H, CH₃CO), 2.13 [m, 6H,

(CH₂)₃-C], 2.05 (s, 9H, CH₃CO), 2.00 (s, 9H, CH₃CO), 1.99 (s, 9H,

CH₃CO), 1.94 (m, 6H, CH₂CO). ¹³C NMR (CDCl₃): δ (ppm) 172.9

(CO dend), 171 (CO phenylalanine), 170.4 (COCH₃), 170.3

(COCH₃), 170.2 (COCH₃), 169.6 (COCH₃), 156.5 (CO benzyl-

oxycarbonyl), 136.6 (C₁benzyloxycarbonyl), 136.3 (C₁phenylalanine),

129.3 (o-phenylalanine), 128.7 (p-phenylalanine), 128.5 (m-phenyl-

alanine), 128.3 (o-benzyloxycarbonyl), 127.7 (p-benzyloxycarbonyl), 127.1

(m-benzyloxycarbonyl), 101.3 (C₁), 70.9 (C₃), 70.6 (C₅), 70.3 (CH₂O),

70 (CH₂O), 68.9 (C₂), 68.7 (CH₂-O-galactosyl), 67.1 (C₄), 67 (CH₂

benzyloxycarbonyl), 61.4 (C₆), 58.7 (C-NH), 57.4 (CH phenylalanine),

39.2(CH₂-NH), 38.3 (CH₂phenylalanine), 30.6 (CH₂CO), 30.5[(CH₂)₃-

C], 20.8 (CH₃CO), 20.65 (CH₃CO), 20.63 (2 CH₃CO).

Compound 30-r-ManOAc: The title compound was prepared as

23-β-GluOAc from 22-Phen and 2-aminoethoxyethoxy-O-2⁰,3⁰,4⁰,6⁰-

tetraacetyl-R-^D-mannopyranose. Pure title compound was obtained

after crystallization from a mixture of methylene chloride/diethyl ether

as a beige powder (yield 56%). MS calcd for C₈₁H₁₁₄N₅O₃₉(MH^þ)

1780.7 and calcd for C₈₁H₁₁₃N₅O₃₉Na (MNa^þ) 1802.7, found 1780.9

and 1802.8. Anal. (C₈₁H₁₁₃N₅O₃₉), 4H₂O calcd: C 52.51, H 6.58, N

3.70. Found: C 52.42, H 6.21, N 4.11. ¹H NMR (CDCl₃): δ (ppm) 7.30

(m, 5H, benzyloxycarbonyl), 7.25 (m, 5H, phenylalanine), 6.45 (broad t,

3H, NH-CH₂), 5.29 (m, 9H, HC₂, HC₃and HC₄), 5.06 (s, 2H, CH₂

benzyloxycarbonyl), 4.88 (s, 3H, HC₁), 4.31 (m, 1H, HC phenyl-

alanine), 4.25 (dd, 3H, J = 5 and 12.2 Hz, H_aC₆), 4.12 (dd, 3H, J =

12 Hz, H_bC₆), 4.03 (m, 3H, HC₅), 3.77 (m, 3H, CH_2a-O-mannosyl),

3.67 (m, 3H, CH_2b-O-mannosyl), 3.61 (m, 6H, CH₂O), 3.5 (m, 6H,

CH₂O), 3.38 (m, 6H, CH₂-NH), 3.03 (m, 2H, CH₂-phenylalanine),

2.15 (s, 9H, CH₃CO), 2.09 (s, 9H, CH₃CO), 2.06 [m, 6H, (CH₂)₃-C],

2.04 (s, 9H, CH₃CO), 1.99 (s, 9H, CH₃CO), 1.97 (m, 6H, CH₂CO).

¹³C NMR (CDCl₃): δ (ppm) 173.3 (CO dend), 170.9 (CO

phenylalanine), 170.8 (COCH₃), 170.2 (COCH₃), 170.1 (COCH₃),

169.8 (COCH₃), 156 (CO benzyloxycarbonyl), 136.6 (C₁benzyl-

oxycarbonyl), 136.3 (C₁phenylalanine), 129.4 (o-phenylalanine), 128.5

(p-phenylalanine), 128.5 (m-phenylalanine), 128.1 (o-benzyloxycarbonyl),

127.9 (p-benzyloxycarbonyl), 126.9 (m-benzyloxycarbonyl), 97.6 (C₁),

69.95 (CH₂O), 69.8 (CH₂O), 69.6 (C₃), 68.9 (C₂), 68.4 (C₅), 66.9

(CH₂-O-mannosyl), 66.1 (C₄), 65.9 (CH₂benzyloxycarbonyl), 62.4 (C₆),

58 (C-NH), 56.9 (CH phenylalanine), 39.3 (CH₂-NH), 38.5 (CH₂

phenylalanine), 30.5 [CH₂CO and (CH₂)₃-C], 20.9 (CH₃CO), 20.7

(CH₃CO), 20.7 (2 CH₃CO).

Compound 31-β-GluOAc: The title compound was prepared as

26-β-GluOAc from 29-β-GluOAc. Pure title compound was obtained

after crystallization from a mixture of methylene chloride/diethyl ether

as beige crystals (yield 70%). MS calcd for C₆₇H₉₆N₅O₃₄(MH^þ)

1514.59, found 1514.7. Anal. (C₆₇H₉₅N₅O₃₄), 4H₂O calcd: C 50.72,

H 6.54, N 4.41. Found: C 50.47, H 6.21, N 4.54. ¹H NMR (CDCl₃): δ

(ppm) 7.3 (m, 5H, phenylalanine), 5.22 (dd, 3H, J = 9.4 Hz, HC₃), 5.07

(dd, 3H, J = 9.4 Hz, HC₄), 4.97 (dd, 3H, J = 9.4 Hz, HC₂), 4.54 (d, 3H,

J = 7.8 Hz, HC₁), 4.27 (dd, 3H, J = 4.6 and 12.3 Hz, H_aC₆), 4.15 (dd, 3H,

J = 12.2 Hz, H_bC₆), 3.39 (d, 6H, J = 4.2 Hz, CH₂-NH), 2.17 [m, 6H,

(CH₂)₃-C], 2.08 (s, 9H, CH₃CO), 2.07 (m, 6H, CH₂CO), 2.06 (s, 9H,

CH₃CO), 2.03 (s, 9H, CH₃CO), 2.00 (s, 9H, CH₃CO). ¹³C NMR

(CDCl₃): δ (ppm) 173.2 (CO dend), 172.3 (CO phenylalanine), 170.7

(COCH₃), 170.2 (COCH₃), 169.6 (COCH₃), 169.4 (COCH₃), 137 (C₁

phenylalanine), 129.5 (o-phenylalanine), 128.8 (p-phenylalanine), 128.4

(m-phenylalanine), 100.8 (C₁), 72.6 (C₃), 71.8 (C₅), 71.3 (C₂), 68.7

(CH₂-O-glucosyl), 68.3 (C₄), 61.8 (C₆), 58.4 (C-NH), 39.3 (CH₂-NH),

30.8 (CH₂CO), 30.5 [(CH₂)₃-C], 20.7 (2 CH₃CO), 20.6 (2 CH₃CO).

Compound 31-β-GalOAc: The title compound was prepared as

26-β-GluOAc from 29-β-GalOAc. Pure title compound was obtained

after crystallization from a mixture of methylene chloride/diethyl ether

as beige crystals (yield 63%). MS calcd for C₆₇H₉₅N₅O₃₄Na (MNa^þ)

1536.59, found 1536.6. Anal. (C₆₇H₉₅N₅O₃₄), 4H₂O calcd: C 50.72, H

6.54, N 4.41. Found: C 50.60, H 6.65, N 4.20. H NMR (CDCl₃): δ

(ppm) 7.29 (m, 5H, phenylalanine), 5.39 (d, 3H, J = 2.6 Hz, HC₄), 5.16

(dd, 3H, J = 7.8 and 10.3 Hz, HC₂), 5.02 (dd, 3H, J = 2.5 and 10.2 Hz,

HC₃), 4.51 (d, 3H, J = 7.8 Hz, HC₁), 4.28 (m, 1H, HC phenylalanine),

4.15 (m, 6H, HC₆), 3.94 (m, 3H, HC₅), 3.85 (m, 3H, CH_2a-O-

galactosyl), 3.67 (m, 3H, CH_2b-O-galactosyl), 3.41 (d, 6H, CH₂-NH),

3.15 (m, 2H, CH₂-phenylalanine), 2.14 (s, 9H, CH₃CO), 2.12 [m, 6H,

(CH₂)₃-C], 2.07 (s, 9H, CH₃CO), 2.05 (s, 9H, CH₃CO), 1.99 (s, 9H,

CH₃CO), 1.99 (m, 6H, CH₂CO). ¹³C NMR (CDCl₃): δ (ppm) 172.9

(CO dend), 172 (CO phenylalanine), 170.4 (COCH₃), 170.2

(COCH₃), 170 (COCH₃), 169.8 (COCH₃), 138 (C₁phenylalanine),

129.9 (o-phenylalanine), 129.4 (p-phenylalanine), 128.7 (m-phenyl-

alanine), 101.3 (C₁), 70.8 (C₅), 70.7 (C₃), 68.9 (C₂), 68.8 (CH₂-O-

galactosyl), 67 (C₄), 61.3 (C₆), 58.8 (C-NH), 57.1 (CH phenylalanine),

39.3 (CH₂-NH), 38.4 (CH₂phenylalanine), 30.8 (CH₂CO), 30.6

[(CH₂)₃-C], 20.8 (CH₃CO), 20.7 (CH₃CO), 20.6 (2 CH₃CO),

20.55 (2 CH₃CO).

Compound 31-r-ManOAc: The title compound was prepared as

26-β-GluOAc from 29-r-ManOAc. Pure title compound was obtained

after crystallization from a mixture of methylene chloride/diethyl ether

as yellow crystals (yield 97%). MS calcd for C₆₇H₉₆N₅O₃₄(MH^þ)

1514.6, found 1514.7. Anal. (C₆₇H₉₅N₅O₃₄), 2H₂O calcd: C 51.90, H

6.44, N 4.52. Found: C 51.4, H 6.00, N 4.39. H NMR (CDCl₃): δ

(ppm) 7.29 (m, 5H, phenylalanine), 5.30 (m, 9H, HC₂, HC₃and HC₄),

4.84 (d, 3H, J = 1.1 Hz, HC₁), 4.26 (dd, 3H, J = 5.4 and 12.3 Hz, H_aC₆),

4.13 (dd, 3H, J = 1.8 and 12 Hz, H_bC₆), 4.0 (m, 3H, HC₅), 3.76 (m, 3H,

CH_2a-O-mannosyl), 3.67 (dd, 1H, J = 6.7 Hz, HC phenylalanine), 3.52

(m, 6H, CH_2b-O-mannosyl and CH_2a-NH), 3.38 (m, 3H, CH_2b-NH),

3.14 (m, 1H, CH_2a-phenylalanine), 3.07 (m, 1H, CH_2b-phenylalanine),

2.16 [m, 6H, (CH₂)₃-C], 2.15 (s, 9H, CH₃CO), 2.10 (s, 9H, CH₃CO),

2.04 (s, 9H, CH₃CO), 2.03 (m, 6H, CH₂CO), 1.98 (s, 9H, CH₃CO).

¹³C NMR (CDCl₃): δ (ppm) 173.5 (CO dend), 170.7 (COCH₃), 170.6

(CO phenylalanine), 170.2 (COCH₃), 170.1 (COCH₃), 169.7

(COCH₃), 136.9 (C₁phenylalanine), 129.5 (o-phenylalanine), 128.7

(p-phenylalanine), 127.1 (m-phenylalanine), 97.5 (C₁), 69.3 (C₂), 69.2

(C₃), 68.6 (C₅), 66.9 (CH₂-O-mannosyl), 65.9 (C₄), 62.4 (C₆), 58.3

(C-NH), 53.7 (CH phenylalanine), 42 (CH₂phenylalanine), 38.8

(CH₂-NH), 31.1 (CH₂CO), 30.5 [(CH₂)₃-C], 20.8 (2 CH₃CO), 20.6

(2 CH₃CO).

Compound 32-β-GluOAc: The title compound was prepared as

26-β-GluOAc from 30-β-GluOAc. Pure title compound was obtained

as beige crystals and used without purification (yield 97%). MS calcd for

C₇₃H₁₀₈N₅O₃₇(MH^þ) 1646.66, found 1646.8. Anal. (C₇₃H₁₀₇N₅O₃₇),

4H₂O calcd: C 51.01, H 6.74, N 4.07. Found: C 50.91, H 6.69, N 4.29.

¹H NMR (CDCl₃): δ (ppm) 7.25 (m, 5H, phenylalanine), 6.44 (broad t,

3H, NH-CH₂), 5.23 (t, 3H, J = 9.4 Hz, HC₃), 5.09 (t, 3H, J = 9.4 Hz,

HC₄), 4.99 (t, 3H, J = 8 Hz, HC₂), 4.59 (d, 3H, J = 7.8 Hz, HC₁), 4.26

(dd, 3H, J = 4.4 and 12.3 Hz, H_aC₆), 4.14 (dd, 3H, J = 1.6 and 12 Hz,

H_bC₆), 3.96 (m, 3H, CH_2a-O-glucosyl), 3.70 (m, 6H, HC₅and CH_2b-O-

glucosyl), 3.61 (m, 7H, CH₂O and CH phenylalanine), 3.5 (m, 6H,

CH₂O), 3.37 (m, 6H, CH₂-NH), 3.14 (m, 1H, CH_2aphenylalanine), 2.75

(m, 1H, CH_2bphenylalanine), 2.14 [m, 6H, (CH₂)₃-C], 2.08 (s, 9H,

CH₃CO), 2.06 (m, 6H, CH₂CO), 2.04 (s, 9H, CH₃CO), 2.02 (s, 9H,

CH₃CO), 1.99 (s, 9H, CH₃CO). ¹³C NMR (CDCl₃): δ (ppm) 173 (CO

dend), 170.7 (COCH₃), 170.2 (COCH₃), 169.8 (CO phenylalanine),

169.6 (COCH₃), 169.4 (COCH₃), 137 (C₁phenylalanine), 129.4 (o-

phenylalanine), 128.7 (p-phenylalanine), 126.8 (m-phenylalanine), 100.8

(C₁), 72.6 (C₃), 71.8 (C₅), 71.3 (C₂), 69.8 (2 CH₂O), 69 (CH₂-O-

glucosyl), 68.3 (C₄), 61.8 (C₆), 57.6 (C-NH), 57 (CH phenylalanine),

40.9 (CH₂phenylalanine), 39.2 (CH₂-NH), 30.9 (CH₂CO), 30.6

[(CH₂)₃-C], 20.7 (2 CH₃CO), 20.6 (2 CH₃CO).

Compound 32-β-GalOAc: The title compound was prepared as

26-β-GluOAc from 30-β-GalOAc. Pure title compound was obtained

2020

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

after crystallization from a mixture of methylene chloride/diethyl ether

as beige crystals (yield 89%). MS calcd for C₇₃H₁₀₈N₅O₃₇(MH^þ)

1646.66, calcd for C₇₃H₁₀₇N₅O₃₇Na (MNa^þ) 1668.6, found 1646.8 and

1668.8. Anal. (C₇₃H₁₀₇N₅O₃₇), 5H₂O calcd: C 50.48, H 6.79, N 4.03.

Found: C 50.73, H 6.33, N 4.59. ¹H NMR (CDCl₃): δ (ppm) 7.27 (m,

5H, phenylalanine), 6.51 (broad t, 3H, NH-CH₂), 5.39 (d, 3H, J = 2.7

Hz, HC₄), 5.19 (dd, 3H, J = 7.8 and 10.2 Hz, HC₂), 5.06 (m, 3H, HC₃),

4.58 (d, 3H, HC₁), 4.26 (m, 1H, HC phenylalanine), 4.14 (m, 6H, HC₆),

3.96 (m, 6H, HC₅and CH_2a-O-galactosyl), 3.71 (m, 3H, CH_2b-O-

galactosyl), 3.62 (m, 6H, CH₂O), 3.52 (m, 6H, CH₂O), 3.39 (m, 6H,

CH₂-NH), 3.14 (m, 2H, CH₂-phenylalanine), 2.14 (s, 9H, CH₃CO),

2.13 [m, 6H, (CH₂)₃-C], 2.05 (s, 9H, CH₃CO), 2.04 (s, 9H, CH₃CO),

1.98 (s, 9H, CH₃CO), 1.98 (m, 6H, CH₂CO). ¹³C NMR (CDCl₃): δ

(ppm) 173 (CO dend), 172.96 (CO phenylalanine), 170.2 (COCH₃),

170 (2COCH₃), 169.5 (COCH₃), 136.9 (C₁phenylalanine), 129.3

(o-phenylalanine), 128.5 (p-phenylalanine), 126.7 (m-phenylalanine),

101.1 (C₁), 70.6 (C₃), 70.4 (C₅), 69.7 (CH₂O), 69.6 (CH₂O), 68.7

(CH₂-O-galactosyl), 68.7 (C₂), 66.9 (C₄), 61.1 (C₆), 57.7 (C-NH), 56.4

(CH phenylalanine), 40.3 (CH₂phenylalanine), 39 (CH₂-NH), 30.7

(CH₂CO), 30.3 [(CH₂)₃-C], 20.6 (CH₃CO), 20.5 (2 CH₃CO), 20.4

(CH₃CO).

4.7 Hz, CH₂O), 3.70 (t, 2H, J = 5 Hz, CH₂O), 3.41 (t, 2H, J = 5 Hz,

CH₂N₃), 2.11 (s, 3H, CH₃CO). ¹³C NMR (CDCl₃): δ (ppm) 171.4

(COCH₃), 70.4 (CH₂O), 69.5 (CH₂O), 63.8 (CH₂OAc), 51 (CH₂N₃),

21.4 (CH₃).

2-(2-Aminoethoxy)ethyl ethanoate, tosylate salt, 35: Azido

compound 34 (3.09 g, 18 mmol) and p-toluenesulfonic acid (3.52 g,

18 mmol) were dissolved in ethyl acetate (100 mL). Palladium (10%)

under carbon (0.6 g) was added. The mixture was stirred under hydrogen

atmosphere (5 bar) overnight at room temperature. The suspension was

filtered over Celite, which was washed with ethanol. The crude solution

was concentrated under vacuum. The title compound was obtained as a

colorless oil. Ether (100 mL) was added and the title compound was

crystallized as a hygroscopic white powder (5.02 g, yield 88%). ¹H NMR

(CDCl₃): δ (ppm) 7.77 (d, 5H, J = 8.1 Hz, CH tosylate and NH₃^þ), 7.19

(d, 2H, J = 8 Hz, CH tosylate), 4.10 (t, 2H, J = 4.7 Hz, CH₂OAc), 3.62 (t,

2H, J = 5.1 Hz, CH₂O), 3.56 (t, 2H, J = 4.7 Hz, CH₂O), 3.09 (t, 2H, J =

5.1 Hz, CH₂O), 2.38 (s, 3H, CH₃), 2.02 (s, 3H, CH₃CO).

4-(Z-N-2-Aminoethanamido)-N¹,N⁷-bis[2-(2-hydroxyethoxy)

ethyl]-4-{3-[2-(2-hydroxyethoxy)ethylamino]-3-oxopropyl}

heptanediamide, 36: The title compound was prepared as 23-β-

GluOAc from 35 (0.220 g, 0.5 mmol) and 22-Gly (0.479 g, 1.5 mmol).

The crude title compound was dried under vacuum and used without

purification (0.282 g, yield 73%). ¹H NMR (CDCl₃): δ (ppm) 7.37 (m,

5H, benzyloxycarbonyl), 7.24 (broad s, 1H, NH), 6.32 (broad t, 3H,

NH), 5.62 (broad t, 1H, J = 5.4 Hz, NH), 5.15 (s, 2H, CH₂

benzyloxycarbonyl), 4.24 (t, 6H, J = 4.7 Hz, CH₂-OAc), 3.78 (d, 2H,

J = 5.7 Hz, CH₂glycine), 3.67 (t, 6H, J = 4.7 Hz, CH₂), 3.55 (t, 6H, J =

5.1 Hz, CH₂-O), 3.42 (dt, 6H, J = 5.1 Hz, CH₂), 2.22 (t, 6H, J = 7.2 Hz,

CH₂-O), 2.10 (s, 9H, CH₃CO), 2.04 (t, 6H, J = 7.5 Hz, CH₂). ¹³C NMR

(CDCl₃): δ (ppm) 173.3 (CO dend), 171.1 (COCH₃), 168.7 (CO

glycine), 156.7 (CO-benzyloxycarbonyl), 136 (C₁Z-phenyl), 128.1 (o-

benzyloxycarbonyl), 127.8 (p-benzyloxycarbonyl), 127.5 (m-benzyloxy-

carbonyl), 69.3 (C-O), 68.5 (C-O), 66.7 (C-benzyloxycarbonyl), 63

(C-O-acetyl), 58.2 (C-NH), 44.6 (C glycine), 38.9 (C-NH), 30.7

[(CH₂)₃-C], 30.4 (C-CO), 20.6 (CH₃CO).

Compound 32-r-ManOAc: The title compound was prepared as

26-β-GluOAc from 30-r-ManOAc. Pure title compound was obtained

after crystallization from a mixture of methylene chloride/diethyl ether

as yellow crystals (yield 88%). MS calcd for C₇₃H₁₀₇N₅O₃₇(MH^þ)

1646.66, found 1647.0. Anal. (C₇₃H₁₀₇N₅O₃₇), 6H₂O calcd: C 49.97, H

6.84, N 3.99. Found: C 49.71, H 6.50, N 4.11. H NMR (CDCl₃): δ

(ppm) 7.3 (m, 5H, phenylalanine), 6.53 (broad t, 3H, NH-CH₂), 5.30

(m, 9H, HC₂, HC₃and HC₄), 4.91 (d, 3H, J = 1.1 Hz, HC₁), 4.27 (dd,

3H, J = 5 and 12.2 Hz, H_aC₆), 4.11 (m, 3H, H_bC₆), 4.04 (m, 3H, HC₅),

3.78 (m, 3H, CH_2a-O-mannosyl), 3.68 (m, 3H, CH_2b-O-mannosyl),

3.63 (m, 6H, CH₂O), 3.51 (m, 6H, CH₂O), 3.39 (m, 6H, CH₂-NH),

3.16 (m, 2H, CH₂-phenylalanine), 2.16 [m, 6H, (CH₂)₃-C], 2.15 (s, 9H,

CH₃CO), 2.10 (s, 9H, CH₃CO), 2.06 (m, 6H, CH₂CO), 2.05 (s, 9H,

CH₃CO), 1.99 (s, 9H, CH₃CO). ¹³C NMR (CDCl₃): δ (ppm) 173

(CO dend), 171.1 (CO phenylalanine), 170.8 (COCH₃), 170.2

(COCH₃), 170 (COCH₃), 169.8 (COCH₃), 138 (C₁phenylalanine),

129.5 (o-phenylalanine), 128.7 (p-phenylalanine), 126.8 (m-phenyl-

alanine), 97.6 (C₁), 70 (CH₂O), 69.9 (CH₂O), 69.6 (C₃), 68.9 (C₂),

68.4 (C₅), 67.1 (CH₂-O-mannosyl), 66.1 (C₄), 62.5 (C₆), 58 (C-NH),

57 (CH phenylalanine), 40.9 (CH₂phenylalanine), 39.2 (CH₂-NH),

30.8 (CH₂CO), 30.5 [(CH₂)₃-C], 20.9 (CH₃CO), 20.7 (CH₃CO), 20.7

(2 CH₃CO).

2-(2-Chloroethoxy)ethyl ethanoate, 33: Diethylene glycol

monochlorohydrin (2.50 g, 20 mmol) and acetic anhydride (2.1 mL,

22 mmol) were stirred at room temperature overnight. Progress of the

reaction was followed by ¹H RMN spectroscopy. The crude mixture was

dissolved in methylene chloride (30 mL), then washed with water,

aqueous sodium bicarbonate solution, and water. The organic phase was

dried over sodium sulfate, filtered, and concentrated under vacuum. The

title compound 34 was used without purification (3.13 gr, yield 94%).

¹H NMR (CDCl₃): δ (ppm) 4.26 (t, 2H, J = 4.7 Hz, CH₂OAc), 3.79 (t,

2H, J = 6.3 Hz, CH₂O), 3.74 (t, 2H, J = 4.7 Hz, CH₂O), 3.65 (t, 2H, J =

5.9 Hz, CH₂Cl), 2.11 (s, 3H, CH₃CO). ¹³C NMR (CDCl₃): δ (ppm)

171.3 (COCH₃), 71.6 (CH₂O), 69.5 (CH₂O), 63.7 (CH₂OAc), 42.9

(CH₂Cl), 21.4 (CH₃).

4-(2-Aminoethanamido)-N¹,N⁷-bis[2-(2-hydroxyethoxy)

ethyl]-4-{3-[2-(2-hydroxyethoxy)ethylamino]-3-oxopropyl}

heptanediamide, 37. The title compound was prepared as 26-β-

GluOAc from 36 (0.282 g, 0.34 mmol). The title compound was used

without purification (0.206 g, yield 87%). ¹H NMR (CDCl₃): δ (ppm)

7.65 (broad s, 1H, NH), 7.31 (broad s, 3H, NH), 4.20 (t, 6H, J = 4.3 Hz,

CH₂-OAc), 3.64 (t, 6H, J = 4.3 Hz, CH₂), 3.52 (broad t, 6H, CH₂-O),

3.36 (broad s, 6H, CH₂), 2.20 (t, 6H, J = 7.2 Hz, CH₂-CO), 2.08 (s, 9H,

CH₃CO), 1.99 (t, 6H, J = 7.5 Hz, CH₂).

General Procedure for the Preparation of Compounds 2-

OAc-15-OAc. All operations were identical with those described

for the synthesis of compound 2-OAc. A representative example is

described below.

Porphyrin 2-OAc: Compound 26-β-GluOAc (200 mg, 0.14

mmol) was added after 5 min to a solution of meso-5-(4-benzoic

acid)-10,15,20-tetraphenylporphyrin (46 mg, 7 ꢀ 10^-5mol) containing

HOBt (14.6 mg, 0.105 mmol), EDC (20 mg, 0.105 mmol), and Et₃N

(45 μL) in dry methylene chloride (20 mL) under argon. The solution

was stirred overnight under argon at room temperature. The crude

mixture was washed with aqueous chlorhydric acid (10%), water,

aqueous sodium hydrogenocarbonate (10%), and water then dried over

sodium sulfate, filtered, and concentrated under vacuum. Pure title

compound was obtained by preparative thin layer chromatography

(silica gel, methylene chloride/methanol, 100/5, v/v) and crystallization

from a mixture of methylene chloride/n-heptane as a red powder, (47

mg, yield 33%). Anal. (C₁₀₅H₁₁₇N₉O₃₅), 6H₂O calcd: C 58.52, H 6.01,

N 5.96. Found: C 58.36, H 5.90, N 5.74. UV-vis spectrum in CH₂Cl₂:

λ_max., nm (ε, L mmol^-1cm^-1) 417.5 (403.7), 515.5 (16), 549 (6.9),

2-(2-Azidoethoxy)ethyl ethanoate, 34:Compound33(3.130 g,

18.8 mmol) and sodium azide (4.9 g, 75 mmol) were stirred in dimethyl

sulfoxide (25 mL) under argon at 100 °C for 1 h 30 min. The solution was

diluted in methylene chloride (100 mL) and washed twice with saturated

aqueous sodium chloride solution (100 mL). The organic phase was dried

over sodium sulfate, filtered, and concentrated under vacuum. The title

compound was used without purification (3.09 g, yield 95%). ¹H NMR

(CDCl₃): δ (ppm) 4.26 (t, 2H, J = 4.7 Hz, CH₂OAc), 3.73 (t, 2H, J =

590 (4.7), 645 (3.4). ¹H NMR (CDCl₃): δ (ppm) 8.86 (s, 6H,

2021

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

HC_{2,8,12,13,17,18}pyrrole), 8.81 (d, 2H, J = 4.5 Hz, HC_3,7pyrrole), 8.31

(m, 4H, m- and o-carboxyphenyl), 8.20 (m, 6H, o-phenyl), 7.91 (broad t,

1H, J = 5.2 Hz, NH-glycine), 7.75 (m, 9H, m- and p-phenyl), 7.44 (s, 1H,

NH-C), 6.92 (broad t, 3H, NH-CH₂), 5.18 (t, 3H, J = 9.4 Hz, HC₃), 5.05

(t, 3H, J = 9.5 Hz, HC₄), 4.98 (dd, 3H, J = 8 and 9.3 Hz, HC₂), 4.50 (d,

3H, J = 8 Hz, HC₁), 4.21 (dd, 2H, HC glycine), 4.21 (dd, 3H, J = 4.5 and

12.2 Hz, H_aC₆), 4.09 (m, 3H, H_bC₆), 3.85 (m, 3H, CH_2a-O-glucosyl),

3.66 (m, 6H, HC₅and CH_2b-O-glucosyl), 3.44 (m, 6H, CH₂NH), 2.30

(m, 6H, CH₂CO), 2.16 [m, 6H, (CH₂)₃-C], 2.07 (s, 9H, CH₃CO), 2.05

(s, 9H, CH₃CO), 1.98 (s, 9H, CH₃CO), 1.97 (s, 9H, CH₃CO), -2.79

(s, 2H, NH). ¹³C NMR (CDCl₃): δ (ppm) 173.7 (CO dend), 170.7

(COCH₃), 170.1 (COCH₃), 169.7 (COCH₃), 169.4 (COCH₃), 168.2

(CO glycine), 167.8 (CO phenyl), 145.8 (C₁carboxyphenyl), 141.9 (C₁

phenyl), 134.5 (o-carboxyphenyl), 134.5 (o-phenyl), 132.7 (p-carboxy-

phenyl), 131.2 (C pyrrole), 127.7 (p-phenyl), 126.7 (m-phenyl), 125.7

(m-carboxyphenyl), 120.4 (meso-C₁₅), 120.3 (meso-C_10,20), 118.5 (meso-

C₅), 100.7 (C₁), 72.6 (C₃), 71.8 (C₅), 71.2 (C₂), 68.7 (CH₂-O-gluco-

syl), 68.2 (C₄), 61.8 (C₆), 58.3 (C-NH), 44.3 (CH₂glycine), 39.4

(CH₂-NH), 30.9 [(CH₂)₃-C], 30.7 (COCH₂), 20.7 (2 CH₃CO), 20.5

(2 CH₃CO).

(CO-dend), 170.6 (COCH₃), 170.4 (COCH₃), 169.6 (COCH₃),

169.3 (COCH₃), 169 (CO glycine), 168.1 (CO phenyl), 146

(C₁carboxyphenyl), 141.8 (C₁phenyl), 134.6 (o-carboxyphenyl),

134.4 (o-phenyl), 132.5 (p-carboxyphenyl), 131 (C pyrrole), 127.7

(p-phenyl), 126.6 (m-phenyl), 125.7 (m-carboxyphenyl), 120.5 (meso-

C₁₅), 120.3 (meso-C_10,20), 118.3 (meso-C₅), 100.7 (C₁), 72.7 (C₃),

71.6 (C₅), 71.2 (C₂), 70.1 (CH₂O), 70 (CH₂O), 68.8 (CH₂-O-

glucosyl), 68.4 (C₄), 61.8 (C₆), 58.5 (C-NH), 44.5 (CH₂glycine),

39.3 (CH₂-NH), 30.6 [(CH₂)₃-C and COCH₂], 20.7 (2 CH₃CO),

20.6 (CH₃CO), 20.5 (CH₃CO).

Porphyrin 6-OAc: The title compound was prepared as 2-OAc

from 27-β-GalOAc. Pure title compound was obtained after crystal-

lization from a mixture of methylene chloride/n-heptane as a red powder

(yield 59%). UV-vis spectrum in CH₂Cl₂: λ_max., nm (ε, L mmol^-

cm^-1) 417.5 (413.6), 515 (16.5), 549.5 (7.2), 590 (4.9), 644.5 (3.5).

¹H NMR (CDCl₃): δ (ppm) 8.85 (s, 6H, HC_{2,8,12,13,17,18}pyrrole), 8.81

(d, 2H, J = 4.7 Hz, HC_3,7pyrrole), 8.39 (m, 2H, m-carboxyphenyl), 8.32

(d, 2H, o-carboxyphenyl), 8.18 (m, 6H, o-phenyl), 7.73 (m, 9H, m- and

p-phenyl), 7.41 (broad s, 1H, NH-C), 6.88 (broad t, 3H, NH-CH₂), 5.39

(d, 3H, J = 2.8 Hz, HC₄), 5.22 (dd, 3H, J = 7.5 and 10.4 Hz, HC₂), 5.14

(dd, 3H, J = 2.8 and 10.4 Hz, HC₃), 4.69 (d, 3H, J = 7.5 Hz, HC₁), 4.32

(m, 2H, CH₂glycine), 4.13 (m, 6H, HC₆), 3.94 (m, 6H, HC₅and CH_2a-

O-galactosyl), 3.73 (m, 3H, CH_2b-O-galactosyl), 3.6 (m, 6H, CH₂O),

3.48 (m, 9H, CH₂O and CH_2aNH), 3.4 (m, 3H, CH_2bNH), 2.36 [m,

6H, (CH₂)₃-C], 2.16 (m, 6H, CH₂CO), 2.14 (s, 9H, CH₃CO), 2.06 (s,

9H, CH₃CO), 2.01 (s, 9H, CH₃CO), 1.99 (s, 9H, CH₃CO), -2.78 (s,

2H, NH). ¹³C NMR (CDCl₃): δ (ppm) 173.2 (CO dend), 170.4

(COCH₃), 170.25 (COCH₃), 170.22 (COCH₃), 169.7 (COCH₃),

169.1 (CO glycine), 168.1 (CO phenyl), 146.1 (C₁carboxyphenyl),

141.8 (C₁phenyl), 134.6 (o-carboxyphenyl), 134.4 (o-phenyl), 132.3 (p-

carboxyphenyl), 131.2 (C pyrrole), 127.7 (p-phenyl), 126.6 (m-phenyl),

125.7 (m-carboxyphenyl), 120.5 (meso-C₁₅), 120.2 (meso-C_10,20), 118.2

(meso-C₅), 101.2 (C₁), 70.8 (C₃), 70.5 (C₅), 70.2 (CH₂O), 69.9

(CH₂O), 68.8 (C₂), 68.7 (CH₂-O-galactosyl), 67 (C₄), 61.3 (C₆),

58.5 (C-NH), 44.5 (CH₂glycine), 39.3 (CH₂-NH), 30.7 [(CH₂)₃-C

and COCH₂], 20.8 (2 CH₃CO), 20.6 (2 CH₃CO).

Porphyrin 3-OAc: The title compound was prepared as 2-OAc

from 26-β-GalOAc. Pure title compound was obtained after crystal-

lization from a mixture of methylene chloride/n-heptane as a red powder

(yield 55%). Anal. (C₁₀₅H₁₁₇N₉O₃₅), 11H₂O calcd: C 55.72, H 6.19, N

5.57. Found: C 55.94, H 6.65, N 5.24. UV-vis spectrum in CH₂Cl₂:

λ_max., nm (ε, L mmol^-1cm^-1) 418 (477.9), 515.5 (19.8), 550 (9.4),

590 (6.8), 645.4 (5.4). ¹H NMR (CDCl₃): δ (ppm) 8.85 (s, 6H,

HC_{2,8,12,13,17,18}pyrrole), 8.80 (d, 2H, J = 4.8 Hz, HC_3,7pyrrole), 8.31 (s,

4H, m- and o-carboxyphenyl), 8.21 (d, 6H, J = 4.7 Hz, o-phenyl), 7.74 (m,

9H, m- and p-phenyl), 6.71 (broad t, 3H, J = 5.4 Hz, NH-CH₂), 5.38 (d,

3H, J = 2.9 Hz, HC₄), 5.18 (dd, 3H, J = 7.8 and 10.4 Hz, HC₂), 5.06 (dd,

3H, J = 3.3 and 10.4 Hz, HC₃), 4.52 (d, 3H, J = 7.8 Hz, HC₁), 4.22 (d,

2H, CH₂glycine), 4.12 (m, 6H, J = 6.6 and 11.2 Hz, HC₆), 3.96 (m, 3H,

J = 6.6 Hz, HC₅), 3.88 (m, 3H, CH_2a-O-galactosyl), 3.70 (m, 3H, CH_2b-

O-galactosyl), 3.45 (d, 6H, CH₂NH), 2.33 (m, 6H, CH₂CO), 2.14 [m,

6H, (CH₂)₃-C], 2.12 (s, 9H, CH₃CO), 2.09 (s, 9H, CH₃CO), 2.02 (s,

9H, CH₃CO), 1.96 (s, 9H, CH₃CO), -2.79 (s, 2H, NH). ¹³C NMR

(CDCl₃): δ (ppm) 173.3 (CO dend), 170.5 (COCH₃), 170.1

(COCH₃), 170 (COCH₃), 169.8 (COCH₃), 168.7 (CO glycine), 168

(CO phenyl), 146 (C₁carboxyphenyl), 142 (C₁phenyl), 134.6 (o-

carboxyphenyl), 134.5 (o-phenyl), 132.8 (p-carboxyphenyl), 131.3 (C

pyrrole), 127.7 (p-phenyl), 126.7 (m-phenyl), 125.7 (m-carboxyphenyl),

120.6 (meso-C₁₅), 120.3 (meso-C_10,20), 118.4 (meso-C₅), 101.3 (C₁),

70.7 (C₃and C₅), 68.9 (C₂), 68.7 (CH₂-O-galactosyl), 66.9 (C₄), 61.3

(C₆), 58.3 (C-NH), 44.5 (CH₂glycine), 39.5 (CH₂-NH), 31.1

[(CH₂)₃-C], 30.8 (COCH₂), 20.9 (CH₃CO), 20.7 (CH₃CO), 20.6

(CH₃CO), 20.5 (CH₃CO).

Porphyrin 8-OAc: The title compound was prepared as 2-OAc

from 28-r-ManOAc. Pure title compound was obtained after crystal-

lization from a mixture of methylene chloride/n-heptane as a red powder

(yield 42%). UV-vis spectrum in CH₂Cl₂: λ_max., nm (ε, L mmol^-1

cm^-1) 417.5 (381.6), 515.5 (14.9), 549 (6.5), 590 (4.4), 645 (3.1). ¹H

NMR (CDCl₃): δ (ppm) 8.85 (s, 6H, HC_{2,8,12,13,17,18}pyrrole), 8.81 (d,

2H, J = 4.7 Hz, HC_3,7pyrrole), 8.32 (s, 4H, m- and o-carboxyphenyl),

8.21 (m, 6H, o-phenyl), 8.06 (broad, 1H, NH glycine), 7.74 (m, 9H, m-

and p-phenyl), 7.42 (broad s, 1H, NH), 7.32 (t, 3H, J = 5.3 Hz, NH-

CH₂), 5.35 (t, 3H, J = 3.1 and 10.1 Hz, HC₃), 5.30 (t, 3H, J = 10 Hz,

HC₄), 5.26 (m, 3H, HC₂), 4.87 (d, 3H, J = 1.2 Hz, HC₁), 4.27 (dd, 3H,

J = 5.1 and 12.4 Hz, H_aC₆), 4.25 (d, 2H, HC glycine), 4.10 (dd, 3H, J =

2.2 and 12.3 Hz, H_bC₆), 4.05 (m, 3H, HC₅), 3.80 (m, 3H, CH_2a-O-

mannosyl), 3.63 (m, 24H, CH₂), 3.46 (m, 6H, CH₂NH), 2.34 (m, 6H,

CH₂CO), 2.15 [m, 6H, (CH₂)₃-C], 2.14 (s, 9H, CH₃CO), 2.08 (s, 9H,

CH₃CO), 2.03 (s, 9H, CH₃CO), 1.99 (s, 9H, CH₃CO), -2.78 (s, 2H,

NH). ¹³C NMR (CDCl₃): δ (ppm) 173.8 (CO dend), 170.8 (COCH₃),

170.03 (COCH₃), 170.02 (COCH₃), 169.6 (COCH₃), 169.1 (CO

glycine), 168.1 (CO phenyl), 145.7 (C₁carboxyphenyl), 141,9 (C₁phenyl),

134.5 (o-carboxyphenyl), 134.4 (o-phenyl), 132.8 (p-carboxyphenyl), 131

(C and C_{2,8,12,13,17,18}pyrrole), 127.7 (p-phenyl), 126.6 (m-phenyl), 125.7

(o-carboxyphenyl), 120.4 (meso-C₁₅), 120.2 (meso-C_10,20), 118.5 (meso-C₅),

97.6 (C₁), 70.5 (CH₂-O), 70.1 (CH₂-O), 69.8 (CH₂-O), 69.7 (CH₂-O),

69.4 (C₂), 69.1 (C₃), 68.3 (C₅), 67.2 (CH₂-O-glucosyl), 65.9 (C₄), 62.3

(C₆), 58.1 (C-NH), 44.3 (CH₂glycine), 39.3 (CH₂-NH), 30.8 [(CH₂)₃-

C], 30.6 (COCH₂), 20.8 (CH₃CO), 20.7 (CH₃CO), 20.6 (CH₃CO).

Porphyrin 9-OAc: The title compound was prepared as 2-OAc

from 31-β-GluOAc. Pure title compound was obtained after

Porphyrin 5-OAc: The title compound was prepared as 2-OAc

from 27-β-GluOAc. Pure title compound was obtained after crystal-

lization from a mixture of methylene chloride/n-heptane as a red powder

(yield 41%). UV-vis spectrum in CH₂Cl₂: λ_max, nm (ε, L mmol^-

cm^-1) 417.5 (419.7), 514.5 (16.9), 549 (7.4), 590 (5.1), 645.5 (3.7).

¹H NMR (CDCl₃): δ (ppm) 8.86 (s, 6H, HC_{2,8,12,13,17,18}pyrrole),

8.79 (d, 2H, J = 4.4 Hz, HC_3,7pyrrole), 8.31 (m, 4H, m- and o-

carboxyphenyl), 8.19 (m, 6H, o-phenyl), 7.75 (m, 9H, m- and p-phenyl),

7.49 (broad s, 1H, NH-C), 6.71 (broad t, 3H, NH-CH₂), 5.28 (t, 3H, J =

9.6 Hz, HC₃), 5.08 (t, 3H, J = 9.5 Hz, HC₄), 5.0 (dd, 3H, J = 7.9 and 9.5

Hz, HC₂), 4.67 (d, 3H, J = 7.5 Hz, HC₁), 4.24 (m, 2H, CH₂glycine),

4.21 (m, 3H, H_aC₆), 4.09 (m, 3H, H_bC₆), 3.93 (m, 3H, CH_2a-O-

glucosyl), 3.76 (m, 3H, CH_2b-O-glucosyl), 3.60 (m, 9H, HC₅and

CH₂O), 3.53 (m, 9H, CH₂O and CH_2a-NH), 3.35 (m, 3H, CH_2b-

NH), 2.36 [m, 6H, (CH₂)₃-C], 2.16 (m, 6H, CH₂CO), 2.06 (s, 9H,

CH₃CO), 2.02 (s, 9H, CH₃CO), 2.01 (s, 9H, CH₃CO), 1.99 (s,

9H, CH₃CO), -2.8 (s, 2H, NH). ¹³C NMR (CDCl₃): δ (ppm) 173.4

2022

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

crystallization from a mixture of methylene chloride/n-heptane as a red

powder (yield 35%). Anal. (C₁₁₂H₁₂₃N₉O₃₅), 7H₂O calcd: C 59.97, H

6.05, N 5.53. Found: C 59.20, H 5.52, N 5.06. UV-vis spectrum in

CH₂Cl₂: λ_max., nm (ε, L mmol^-1cm^-1) 418 (471.2), 515.5 (19.2),

589.5 (4.5), 644.5 (3.2). H NMR (CDCl₃): δ (ppm) 8.85 (s, 6H,

HC_{2,8,12,13,17,18}pyrrole), 8.75 (d, 2H, J = 4.8 Hz, HC_3,7pyrrole), 8.29 (d,

4H, J = 8.1 Hz, m- and o-carboxyphenyl), 8.22 (m, 6H, o-phenyl), 7.77

(m, 9H, m- and p-phenyl), 7.42 (m, 5H, phenylalanine), 6.98 (broad t,

3H, NH-CH₂), 5.45 (dd, 3H, J = 3.4 and 10 Hz, HC₃), 5.34 (dd, 3H, J =

1.5 and 3.3 Hz, HC₂), 5.27 (m, 3H, J = 10 Hz, HC₄), 4.87 (d, 3H, J = 0.8

Hz, HC₁), 4.82 (m, 1H, HC phenylalanine), 4.25 (dd, 3H, J = 5.4 and

12.2 Hz, H_aC₆), 4.14 (m, 3H, H_bC₆), 4.07 (m, 3H, HC₅), 3.8 (m, 3H,

CH_2a-O-mannosyl), 3.55 (m, 6H, CH_2b-O-mannosyl and CH_2aNH),

3.43 (m, 3H, CH_2bNH), 3.24 (m, 2H, CH₂phenylalanine), 2.22 (m, 6H,

CH₂CO), 2.12 [m, 6H, (CH₂)₃-C], 2.12 (s, 9H, CH₃CO), 2.09 (s, 9H,

CH₃CO), 2.00 (s, 9H, CH₃CO), 1.99 (s, 9H, CH₃CO), -2.79 (s, 2H,

NH). ¹³C NMR (CDCl₃): δ (ppm) 173.7 (CO dend), 171 (CO

phenylalanine), 170.8 (COCH₃), 170.3 (COCH₃), 170.2 (COCH₃),

169.7 (COCH₃), 168.2 (CO phenyl), 146 (C₁carboxyphenyl), 141.9

(C₁phenyl), 136.9 (C₁phenylalanine), 134.6 (o-carboxyphenyl),

134.5 (o-phenyl), 132.7 (p-carboxyphenyl), 132.2 (p-phenyl), 131.2

(C pyrrole), 129.3 (o-phenylalanine), 128.7 (p-phenylalanine), 127.7

(m-phenylalanine), 126.7 (m-phenyl), 125.7 (m-carboxyphenyl),

120.5 (meso-C₁₅), 120.2 (meso-C_10,20), 118.4 (meso-C₅), 97.7 (C₁),

69.5 (C₂), 69.2 (C₃), 68.6 (C₅), 67.1 (CH₂-O-mannosyl), 66 (C₄),

62.4 (C₆), 58.8 (C-NH), 56.6 (CH phenylalanine), 38.9 (CH₂-NH),

37.9 (CH₂phenylalanine), 31.4 [(CH₂)₃-C], 30.7 (COCH₂), 20.9

(CH₃CO), 20.74 (CH₃CO), 20.67 (CH₃CO), 20.63 (CH₃CO).

Porphyrin 12-OAc: The title compound was prepared as 2-OAc

from 32-β-GluOAc. Pure title compound was obtained after crystal-

lization from a mixture of methylene chloride/n-heptane as a red powder

(yield 39%). UV-vis spectrum in CH₂Cl₂: λ_max., nm (ε, L mmol^-1

550 (9.2), 590 (6.6), 645.5 (5.2). ¹H NMR (CDCl₃): δ (ppm) 8.85 (s,

6H, HC_{2,8,12,13,17,18}pyrrole), 8.79 (d, 2H, J = 4.3 Hz, HC_3,7pyrrole),

8.30 (d, 4H, J = 8 Hz, m- and o-carboxyphenyl), 8.20 (d, 6H, J = 5.7 Hz, o-

phenyl), 7.77 (m, 9H, m- and p-phenyl), 7.41 (m, 5H, phenylalanine),

6.44 (broad t, 3H, NH-CH₂), 5.19 (dd, 3H, J = 9.4 Hz, HC₃), 5.06 (dd,

3H, J = 9.6 Hz, HC₄), 5.0 (dd, 3H, J = 9.4 Hz, HC₂), 4.94 (d, 1H, J = 7.0

Hz, HC phenylalanine), 4.52 (d, 3H, J = 7.8 Hz, HC₁), 4.20 (dd, 3H, J =

4.6 and 12.2 Hz, H_aC₆), 4.11 (dd, 3H, J = 10.8 Hz, H_bC₆), 3.85 (m, 3H,

CH_2a-O-glucosyl), 3.7 (m, 3H, HC₅), 3.68 (m, 3H, CH_2b-O-glucosyl),

3.43 (d, 6H, J = 4.4 Hz, CH₂NH), 3.32 (d, 2H, J = 6.7 Hz, CH₂

phenylalanine), 2.16 [m, 6H, (CH₂)₃-C], 2.05 (s, 9H, CH₃CO), 2.02 (s,

9H, CH₃CO), 2.01 (m, 6H, CH₂CO), 1.98 (s, 9H, CH₃CO), 1.96 (s,

9 H, CH₃CO), -2.79 (s, 2H, NH). ¹³C NMR (CDCl₃): δ (ppm) 173.2

(CO dend), 170.7 (COCH₃), 170.6 (CO phenylalanine), 170.1

(COCH₃), 169.6 (COCH₃), 169.4 (COCH₃), 167.6 (CO phenyl),

145.9 (C₁carboxyphenyl), 142 (C₁phenyl), 136.8 (C₁phenylalanine),

134.7 (o-carboxyphenyl), 134.5 (o-phenyl), 133 (p-carboxyphenyl),

132.2 (p-phenyl), 131.5 (C pyrrole), 129.6 (o-phenylalanine), 128.8

(p-phenylalanine), 127.8 (m-phenylalanine), 126.7 (m-phenyl), 125.6

(m-carboxyphenyl), 120.5 (meso-C₁₅), 120.4 (meso-C_10,20), 118.4 (meso-

C₅), 100.8 (C₁), 72.6 (C₃), 71.8 (C₅), 71.3 (C₂), 68.8 (CH₂-O-

glucosyl), 68.3 (C₄), 61.8 (C₆), 58.4 (C-NH), 56 (CH phenylalanine),

39.4 (CH₂-NH), 38.2 (CH₂phenylalanine), 30.9 [(CH₂)₃-C], 30.6

(COCH₂), 20.74 (CH₃CO), 20.71 (CH₃CO), 20.5 (2 CH₃CO).

Porphyrin 10-OAc: The title compound was prepared as 2-OAc

from 31-β-GalOAc. Pure title compound was obtained after crystal-

lization from a mixture of methylene chloride/n-heptane as a red powder

(yield 62%). Anal. (C₁₁₂H₁₂₃N₉O₃₅), 3H₂O calcd: C 60.89, H 5.89, N

5.71. Found: C 60.91, H 5.69, N 5.25. UV-vis spectrum in CH₂Cl₂:

λ_max., nm (ε, L mmol^-1cm^-1) 418 (491.2), 515.5 (19.9), 550 (9.7),

cm^-1) 417.5 (392.6), 515 (15.5), 550 (6.8), 589.5 (4.6), 645 (3.3). ¹H

NMR (CDCl₃): δ (ppm) 8.85 (s, 6H, HC_{2,8,12,13,17,18}pyrrole), 8.78 (d,

2H, J = 4.3 Hz, HC_3,7pyrrole), 8.29 (m, 4H, m- and o-carboxyphenyl),

8.21 (d, 6H, o-phenyl), 7.75 (m, 9H, m- and p-phenyl), 7.41 (m, 5H,

phenylalanine), 6.57 (broad t, 3H, NH-CH₂), 5.31 (t, 3H, J = 9.5 Hz,

HC₃), 5.08 (m, 3H, HC₄), 5.0 (m, 3H, HC₂), 4.97 (m, 1H, HC

phenylalanine), 4.69 (d, 3H, J = 7.7 Hz, HC₁), 4.19 (dd, 3H, J = 4.4

and 12.2 Hz, H_aC₆), 4.05 (m, 3H, J = 12.2 Hz, H_bC₆), 3.93 (m, 3H,

CH_2a-O-glucosyl), 3.73 (m, 3H, CH_2b-O-glucosyl), 3.64 (m, 9H, HC₅

and CH₂O), 3.50 (m, 9H, CH₂O and CH_2a-NH), 3.33 (m, 5H, CH_2b-

NH and CH₂phenylalanine), 2.16 [m, 6H, (CH₂)₃-C], 2.06 (m, 6H,

CH₂CO), 2.05 (s, 9H, CH₃CO), 2.01 (s, 18H, CH₃CO), 1.99 (s, 9H,

CH₃CO), -2.8 (s, 2H, NH). ¹³C NMR (CDCl₃): δ (ppm) 173.2 (CO

dend), 171 (CO phenylalanine), 170.7 (COCH₃), 170.6 (COCH₃),

169.6 (COCH₃), 169.3 (COCH₃), 167.7 (CO phenyl), 146 (C₁

carboxyphenyl), 141.9 (C₁phenyl), 136.6 (C₁phenylalanine), 134.7

(o-carboxyphenyl), 134.5 (o-phenyl), 133 (p-carboxyphenyl), 131.3 (C

pyrrole), 129.5 (o-phenylalanine), 128.9 (p-phenylalanine), 127.8

(m-phenylalanine), 126.7 (m-phenyl and p-phenyl), 125.7 (m-

carboxyphenyl), 120.7 (meso-C₁₅), 120.4 (meso-C_10,20), 118.1 (meso-

C₅), 100.8 (C₁), 72.7 (C₃), 71.7 (C₅), 71.3 (C₂), 70.3 (CH₂O), 70.1

(CH₂O), 68.8 (CH₂-O-glucosyl), 68.4 (C₄), 61.8 (C₆), 58.5 (C-NH),

56 (CH phenylalanine), 39.3 (CH₂-NH), 38.2 (CH₂phenylalanine),

30.3 [(CH₂)₃-C and COCH₂], 20.7 (2 CH₃CO), 20.63 (CH₃CO),

20.61 (CH₃CO).

590 (6.9), 645.5 (5.4). ¹H NMR (CDCl₃): δ (ppm) 8.85 (s, 6H,

HC_{2,8,12,13,17,18}pyrrole), 8.80 (d, 2H, J = 4.5 Hz, HC_3,7pyrrole), 8.31 (s,

4H, m- and o-carboxyphenyl), 8.20 (m, 6H, o-phenyl), 7.76 (m, 9H, m-

and p-phenyl), 7.45 (m, 5H, phenylalanine), 6.44 (broad t, 3H, J =

5.1 Hz, NH-CH₂), 5.36 (d, 3H, J = 2.7 Hz, HC₄), 5.20 (dd, 3H, J = 7.8

and 10.4 Hz, HC₂), 5.03 (dd, 3H, J = 3.3 and 10.4 Hz, HC₃), 4.94 (d, 1H,

J = 6.7 Hz, HC phenylalanine), 4.51 (d, 3H, J = 7.8 Hz, HC₁), 4.15 (m,

3H, J = 6.6 and 12.2 Hz, H_aC₆), 4.09 (m, 3H, J = 6.6 and 12.2 Hz, H_bC₆),

3.92 (m, 3H, J = 6.6 Hz, HC₅), 3.88 (m, 3H, CH_2a-O-galactosyl), 3.71

(m, 3H, CH_2b-O-galactosyl), 3.45 (d, 6H, J = 5 Hz, CH₂NH), 3.31 (m,

2H, CH₂phenylalanine), 2.17 [m, 6H, (CH₂)₃-C], 2.17 (s, 9H,

CH₃CO), 2.06 (s, 9H, CH₃CO), 2.05 (s, 9H, CH₃CO), 2.01 (m, 6H,

CH₂CO), 1.99 (s, 9H, CH₃CO), -2.79 (s, 2H, NH). ¹³CNMR (CDCl₃):

δ (ppm) 173.2 (CO dend), 170.6 (CO phenylalanine), 170.4 (COCH₃),

170.1 (2 COCH₃), 169.8 (COCH₃), 167.5 (CO phenyl), 146 (C₁

carboxyphenyl), 142 (C₁phenyl), 136.8 (C₁phenylalanine), 134.7

(o-carboxyphenyl), 134.5 (o-phenyl), 132.8 (p-carboxyphenyl), 132.3 (p-

phenyl), 131 (C pyrrole), 129.6 (o-phenylalanine), 128.8 (p-phenylala-

nine), 127.8 (m-phenylalanine), 126.7 (m-phenyl), 125.6 (m-carboxyphenyl),

120.5 (meso-C₁₅), 120.3 (meso-C_10,20), 118.3 (meso-C₅), 101.3 (C₁),

70.7 (C₃and C₅), 68.8 (C₂), 68.8 (CH₂-O-galactosyl), 67 (C₄), 61.3

(C₆), 58.4 (C-NH), 56.1 (CH phenylalanine), 39.4 (CH₂-NH), 38.2

(CH₂phenylalanine), 30.8 [(CH₂)₃-C], 30.6 (COCH₂), 20.9

(CH₃CO), 20.65 (CH₃CO), 20.55 (2 CH₃CO).

Porphyrin 13-OAc: The title compound was prepared as 2-OAc

from 32-β-GalOAc. Pure title compound was obtained after crystal-

lization from a mixture of methylene chloride/n-heptane as a red powder

(yield 54%). Anal. (C₁₁₈H₁₃₅N₉O₃₈), 16H₂O calcd: C 55.03, H 6.54, N

4.89. Found: C 55.07, H 5.49, N 4.9. UV-vis spectrum in CH₂Cl₂:

λ_max., nm (ε, L mmol^-1cm^-1) 418 (402), 515 (15.9), 550.5 (6.9),

Porphyrin 11-OAc: The title compound was prepared as 2-OAc

from 31-r-ManOAc. Pure title compound was obtained after crystal-

lization from a mixture of methylene chloride/n-heptane as a red powder

(yield 79%). Anal. (C₁₁₂H₁₂₃N₉O₃₅), 10H₂O calcd: C 57.6, H 6.17,

N 5.40. Found: C 57.77, H 5.78, N 5.21. UV-vis spectrum in CH₂Cl₂:

λ_max., nm (ε, L mmol^-1cm^-1) 417.5 (390), 515 (15.1), 549.5 (7.1),

590 (4.7), 645 (3.4). ¹H NMR (CDCl₃): δ (ppm) 8.85 (s, 6H,

HC_{2,8,12,13,17,18}pyrrole), 8.76 (m, 2H, HC_3,7pyrrole), 8.29 (m, 4H,

m- and o-carboxyphenyl), 8.22 (m, 6H, o-phenyl), 7.76 (m, 9H, m- and

p-phenyl), 7.42 (m, 5H, phenylalanine), 6.70 (broad t, 3H, NH-CH₂),

5.38 (d, 3H, HC₄), 5.22 (m, 6H, HC₂and HC₃), 4.96 (m, 1H, HC

2023

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

phenylalanine), 4.77 (d, 3H, J = 7.4 Hz, HC₁), 4.10 (m, 6H, HC₆), 3.94

(m, 6H, HC₅and CH_2a-O-galactosyl), 3.80 (m, 3H, CH_2b-O-galac-

tosyl), 3.52 (m, 9H, CH_2aNH and CH₂O), 3.31 (m, 5H, CH₂

phenylalanine and CH_2bNH), 2.13 (s, 9H, CH₃CO), 2.07 (s, 9H,

CH₃CO), 2.07 [m, 6H, (CH₂)₃-C], 2.02 (s, 9H, CH₃CO), 2.00 (m,

6H, CH₂CO), 1.96 (s, 9H, CH₃CO), -2.79 (s, 2H, NH). ¹³C NMR

(CDCl₃): δ (ppm) 173.1 (CO dend), 171 (CO phenylalanine), 170.7

(COCH₃), 170.3 (2 COCH₃), 169.7 (COCH₃), 168 (CO phenyl), 146

(C₁carboxyphenyl), 141.9 (C₁phenyl), 136.6 (C₁phenylalanine),

134.6 (o-carboxyphenyl), 134.4 (o-phenyl), 132.2 (p-carboxyphenyl),

132 (p-phenyl), 131.4 (C pyrrole), 129.4 (o-phenylalanine), 128.9 (p-

phenylalanine), 127.7 (m-phenylalanine), 126.6 (m-phenyl), 125.6 (m-

carboxyphenyl), 121 (meso-C₁₅), 120.4 (meso-C_10,20), 118(meso-C₅), 101.3

(C₁), 71 (C₃), 70.6 (C₅), 70.1 (2 CH₂O), 68.9 (C₂), 68.6 (CH₂-O-

galactosyl), 67.2 (C₄), 61.5 (C₆), 58.6 (C-NH), 56.9 (CH phenylalanine),

39.3 (CH₂-NH), 38.1 (CH₂phenylalanine), 30.5 [(CH₂)₃-C], 30.2

(COCH₂), 20.9 (CH₃CO), 20.64 (CH₃CO), 20.63 (2 CH₃CO).

C₅), 69.5 (CH₂), 68.9 (CH₂), 63.4 (CH₂OAc), 58,1 (C-NH), 44.6 (CH₂

glycine), 39.4 (CH₂-NH), 30.9 (CH₂), 20.9 (CH₃CO).

General Procedure for the Preparation of Compounds

1-15. All operations were identical with those described for the

synthesis of compound 1. A representative example is described below.

5-{p-N-[Tris(O-β-D-galactopyranosyloxy)methyl]-N^r-glyci-

neamidophenyl}-10,15,20-triphenylporphyrin, 1: The pera-

cetylated porphyrin 1-OAc was dissolved (75 mg, 0.04 mmol) in dry

methanol (10 mL) and dry methylene chloride (5 mL) then a solution of

sodium methanolate in methanol (100 μL, 1 M) was added. The

solution was stirred during 4 h at room temperature. IWT TMD-8

ion-exchange resin (400 mg) was added and the suspension was slowly

stirred 30 min then filtered. The resin was washed with methanol and

pyridine. The solution was concentrated under vacuum. The title

compound 1 was obtained as a red powder and used without other

purification (55 mg, yield 95%). MALTI-TOF calcd for C₆₉H₇₂N₆O₂₀

(MH^þ) 1305.48, found 1305.49, calcd for (MNa^þ) 1327.47, found

1327.51, calcd for (MK^þ) 1343.44, found 1343.48. Anal. (C₆₉H₇₂N₆O₂₀)

calcd: C 63.49, H 5.56, N 6.44. Found: C 63.85, H 5.23, N 6.05. UV-vis

Porphyrin 14-OAc: The title compound was prepared as 2-OAc

from 32-r-ManOAc. Pure title compound was obtained after crystal-

lization from a mixture of methylene chloride/n-heptane as a red powder

(yield 30%). UV-vis spectrum in CH₂Cl₂: λ_max., nm (ε, L mmol^-1

spectrum in MeOH/pyridine (24/1, v/v): λ_max, nm (ε, L mmol^-1cm^-1

)

414 (378.5), 513 (17), 547 (8.8), 588.5 (6.7), 644.5 (5.5). H NMR

(pyridine-d₅) δ (ppm) 9.68 (t, 1H, NHCH₂), 9.02 (m, 8H, pyrrole), 8.31

(d, 2H, o⁰-phenyl), 8.23 (d, 8H, C_orthophenyl), 7.75 (2 t and 1 d, 19H, m-

and p-phenyl), 7.00-6.25 (broad, 12H, OH), 4.94 (d, 9H, J = 7.5 Hz, HC₁

and CH₂O-Gal), 4.73 (d, 2H, CH₂NH), 4.62 (d, 3H, J=4.6 Hz, HC₂), 4.53

(m, 6H, HC₄and CH₂O-galactosyl), 4.43 (d, 6H, J = 4.6 Hz, H_aC₆and

H_bC₆), 4.15 (dd, 3H, J = 1.3 and 9 Hz, HC₃), 4.05 (t, 3H, J = 7.8 Hz, HC₅),

-2.44 (s, 2H, NH). ¹³C NMR (pyridine-d₅): δ (ppm) 170.9 (CONH),

168.7 (CONH), 145.8 (C₁carboxyphenyl), 142.9 (C₁phenyl), 136.1, 135

(o-phenyl and o-carboxyphenyl), 132.2 (C pyrrole), 128.7 (p-phenyl),

127.7 (m-phenyl), 127.2 (m-carboxyphenyl), 121.4 (meso-C₁₅), 121.3

(meso-C_10,20), 120.2 (meso-C₅), 106.9 (C₁), 77.5 (C₅), 75.5 (C₃), 73.3

(C₂), 71 (C₄), 70.3 (CH₂O-galactosyl), 62.9 (C₆), 61.8 (C_quattris), 45.2

(CH₂NH).

cm^-1) 417.5 (358), 515 (14.3), 550 (6.2), 590.5 (4.3), 643 (3.1). H

NMR (CDCl₃): δ (ppm) 8.85 (s, 6H, HC_{2,8,12,13,17,18}pyrrole), 8.79 (d,

2H, J = 4.7 Hz, HC_3,7pyrrole), 8.28 (d, 2H, J = 8.0 Hz, o-carboxyphenyl),

8.21 (m, 8H, o-phenyl and m-carboxyphenyl), 7.75 (m, 9H, m- and p-

phenyl), 7.37 (m, 5H, phenylalanine), 7.30 (broad s, 1H, NH

phenylalanine), 6.68 (broad t, 3H, NH-CH₂), 5.36 (m, 3H, HC₃),

5.28 (m, 6H, HC₄and HC₂), 4.91 (m, 4H, HC₁and CH phenylalanine),

4.26 (dd, 3H, J = 5 and 12.2 Hz, H_aC₆), 4.11 (dd, 3H, J = 2 and 12.3 Hz,

H_bC₆), 4.05 (m, 3H, HC₅), 3.77 (m, 3H, CH_2a-O-mannosyl), 3.64 (m,

9H, CH_2b-O-mannosyl and CH₂O), 3.56 (m, 6H, CH₂O), 3.45 (m, 6H,

CH₂-NH), 3.29 (m, 2H, CH₂phenylalanine), 2.20 [m, 6H, (CH₂)₃-C],

2.13 (s, 9H, CH₃CO), 2.08 (m, 6H, CH₂CO), 2.07 (s, 9H, CH₃CO),

2.02 (s, 9H, CH₃CO), 1.98 (s, 9H, CH₃CO), -2.78 (s, 2H, NH). ¹³

NMR (CDCl₃): δ (ppm) 173.4 (CO dend), 170.7 (COCH₃), 170.6 (CO

phenylalanine), 170.2 (COCH₃), 170 (COCH₃), 169.7 (COCH₃), 167.5

(CO phenyl), 145.8 (C₁carboxyphenyl), 142 (C₁phenyl), 136.8 (C₁

phenylalanine), 134.53 (o-carboxyphenyl), 134.47 (o-phenyl), 133.1 (p-

carboxyphenyl), 131.1 (C pyrrole), 129.5 (o-phenylalanine), 128.7 (p-

phenylalanine), 127.7 (p-phenyl and m-phenylalanine), 126.66 (m-phenyl),

125.6 (m-carboxyphenyl), 120.6 (meso-C₁₅), 120.3 (meso-C_10,20), 118.5

(meso-C₅), 97.5 (C₁), 70 (CH₂O), 69.8 (CH₂O), 69.6 (C₃), 69 (C₂),

68.3 (C₅), 67 (CH₂-O-mannosyl), 66.1 (C₄), 62.4 (C₆), 58.3 (C-NH),

56.1 (CH phenylalanine), 39.4 (CH₂-NH), 38.3 (CH₂phenylalanine),

30.9 [(CH₂)₃-C], 30.6 (COCH₂), 20.9 (CH₃CO), 20.69 (CH₃CO),

20.67 (2 CH₃CO).

Porphyrin 2: The title compound was deprotected as in compound

1 from peracetylated porphyrin 2-OAc. Product 2 was obtained as

a red powder and used without other purification (yield 89%). HPLC Rt =

13.51 min. MALDI-TOF MS calcd for C₈₁H₉₄N₉O₂₃(MH^þ) 1560.64.

Found: 1560.70. UV-vis spectrum in MeOH/pyridine (24/1, v/v):

λ_max, nm (ε, L mmol^-1cm^-1) 414 (286.1), 512.5 (11.9), 546.5 (5.3),

589 (3.6), 644 (2.6). ¹H NMR (pyridine-d₅): δ (ppm) 10.01 (m, 1H, NH

glycine), 9.06 (d, 2H, J = 4.6 Hz, HC_3,7pyrrole), 9.03 (m, 6H,

HC_{2,8,12,13,17,18}pyrrole), 8.76 (d, 2H, J = 7.4 Hz, m-carboxyphenyl), 8.62

(broad s, 3H, NH-CH₂), 8.40 (d, 2H, J = 7.7 Hz, o-carboxyphenyl), 8.36

(m, 6H, o-phenyl), 7.79 (m, 9H, m- and p-phenyl), 4.88 (d, 3H, J = 7.3 Hz,

HC₁), 4.69 (m, 2H, CH₂glycine), 4.57 (m, 3H, H_aC₆), 4.34 (m, 3H,

H_bC₆), 4.23 (m, 9H, HC₃, HC₄and CH_2a-O-glucosyl), 4.04 (m, 3H, HC₂),

3.97 (m, 6H, HC₅and CH_2b-O-glucosyl), 3.76 (m, 6H, CH₂NH), 2.69 (m

6H, CH₂CO), 2.56 (m, 6H, [(CH₂)₃-C]), -2.44 (s, 2H, NH). ¹³C NMR

(pyridine-d₅): δ (ppm) 173.9 (CO-den), 169.6 (CO glycine), 168.6 (CO

phenyl), 145.2 (C₁carboxyphenyl), 142.1 (C₁phenyl), 134.8 (o-carbox-

yphenyl and o-phenyl), 134.1 (p-carboxyphenyl), 131.5 (C pyrrole), 128.1

(p-phenyl), 127.2 (m-phenyl), 126.7 (m-carboxyphenyl), 120.8 (meso-C₁₅),

120.6 (meso-C_10,20), 119.5 (meso-C₅), 104.7 (C₁), 78.2 (C₃and C₅), 75

(C₂), 71.4 (C₄), 69.4 (CH₂-O-glucosyl), 62.5 (C₆), 58.7 (C-NH), 44.6

(CH₂glycine), 40.1 (CH₂-NH), 31.3 [(CH₂)₃-C], 30.8 (COCH₂).

Porphyrin 3: The title compound was deprotected as in compound

1 from peracetylated porphyrin 3-OAc. Pure product was obtained

as a red powder and used without other purification (yield 92%). HPLC

Rt = 13.56 min. MALDI-TOF MS calcd for C₈₁H₉₄N₉O₂₃(MH^þ)

1560.64, found 1560.57. UV-vis spectrum in MeOH/pyridine (24/1,

v/v): λ_max, nm (ε, L mmol^-1cm^-1) 414 (306.1), 512.5 (12.6), 547

Porphyrin 15-OAc: The title compound was prepared as 2-OAc

from 37. Pure title compound was obtained after crystallization from a

mixture of methylene chloride/n-heptane as a red powder (yield 86%).

Anal. (C₇₅H₈₁N₉O₁₄), 3 H₂O calcd: C 64.97, H 6.32, N 9.09. Found: C

65.29, H 6.16, N 8.88. UV-vis spectrum in CH₂Cl₂: λ_max., nm (ε,

L mmol^-1cm^-1) 417.5 (436.9), 515 (17), 549.5 (7.4), 590 (5), 645

(3.5). ¹H NMR (CDCl₃): δ (ppm) 8.83 (s, 6H, HC_{2,8,12,13,17,18}pyrrole),

8.79 (d, 2H, J = 4.8 Hz, HC_3,7pyrrole), 8.30 (s, 3H, m- and o-

carboxyphenyl), 8.20 (broad s, 1H, NH glycine), 8.16 (dd, 6H, J = 7.5

and 1.8 Hz, o-phenyl), 7.70 (m, 9H, m- and p-phenyl), 7.53 (broad, 1H,

NH glycine), 7.10 (t, 3H, J = 5.1 Hz, NH), 4.23 (d, 2H, J = 5.1 Hz, CH₂

glycine), 4.20 (m, 6H, CH₂OAc), 3.62 (m, 6H, CH₂), 3.55 (m, 6H,

CH₂), 3.43 (m, 6H, CH₂-NH), 2.36 (m, 6H, CH₂), 2.15 (m, 6H, CH₂),

2.03 (s, 9H, CH₃CO), -2.79 (s, 2H, NH). ¹³C NMR (CDCl₃): δ (ppm)

173.8 (CO dend), 170.8 (COCH₃), 169.3 (CO glycine), 168.3 (CO

phenyl), 146 (C₁carboxyphenyl), 141.8 (C₁phenyl), 134.6 (o-phenyl and

o-carboxyphenyl and CO-phenyl), 131 (C pyrrole), 128 (p-phenyl), 126.4

(m-phenyl), 125.8 (m-carboxyphenyl), 120.3 (meso-C_10,15,20), 118.5 (meso-

(5.6), 588.5 (3.7), 645 (2.6). H NMR (pyridine-d₅): δ (ppm) 9.97

(broad s, 1H, NH glycine), 9.08 (d, 2H, J = 4.3 Hz, HC_3,7pyrrole), 9.03

2024

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

(s, 4H, HC_12,13,17,18pyrrole), 8.76 (d, 2H, HC_2,8pyrrole), 8.57 (m, 2H,

m-carboxyphenyl), 8.37 (m, 8H, o-carboxyphenyl and o-phenyl), 7.80

(m, 9H, m- and p-phenyl), 7.12 (t, 3H, OH), 6.84 (t, 3H, OH), 6.62 (t,

3H, OH), 6.46 (t, 3H, OH), 4.8 (d, 3H, J = 7.4 Hz, HC₁), 4.64 (m, 2H,

CH₂glycine), 4.46 (m, 12H, HC_2,4,6), 4.18 (m, 6H, CH_2a-O-galactosyl

and HC₃), 4.07 (m, 3H, HC₅), 3.99 (m, 3H, CH_2b-O-galactosyl), 3.72

(m, 6H, CH₂-NH), 2.62 [broad s, 6H, (CH₂)₃-C], 2.52 (broad s, 6H,

CH₂-CO), -2.43 (s, 2H, NH). ¹³C NMR (pyridine-d₅): δ (ppm) 173.9

(CO-den), 169.7 (CO glycine), 168.6 (CO carboxyphenyl), 145.3 (C₁

carboxyphenyl), 142.3 (C₁phenyl), 134.8 (o-phenyl and o-carboxyphenyl),

134.2 (p-carboxyphenyl), 131.7 (C pyrrole), 128.2 (p-phenyl), 127.7 (m-

phenyl), 126.8 (m-carboxyphenyl), 120.9 (meso-C₁₅), 120.8 (meso-C_10,20),

119.7 (meso-C₅), 105.3 (C₁), 77 (C₅), 75.2 (C₃), 72.6 (C₂), 70.3 (C₄), 69.5

(CH₂-O-galactosyl), 62.4 (C₆), 58.8 (C-NH), 44.7 (CH₂glycine), 40.4

(CH₂-NH), 31.5 [(CH₂)₃-C], 31 (CH₂CO).

Rt = 13.51 min. MALDI-TOF MS calcd for C₈₇H₁₀₆N₉O₂₆(MH^þ)

1692.72, found 1692.73. UV-vis spectrum in MeOH/pyridine (24/1,

v/v): λ_max, nm (ε, L mmol^-1cm^-1) 414 (294.7), 512.5 (11.6), 548

3₁

(5.9), 590.5 (3.7), 643.5 (2.2). H NMR (pyridine-d₅): δ (ppm) 9.92

(broad s, 1H, NH glycine), 9.07 (d, 2H, J = 4.7 Hz, HC_3,7pyrrole), 9.03

(s, 4H, HC_12,13,17,18pyrrole), 9.02 (d, 2H, J = 4.7 Hz, HC_2,8pyrrole),

8.76 (d, 2H, m-carboxyphenyl), 8.59 (broad t, 3H, NH-CH₂), 8.39 (m,

2H, o-carboxyphenyl), 8.37 (m, 6H, o-phenyl), 7.80 (m, 9H, m- and p-

phenyl), 7.20 (t, 3H, OH), 6.77 (t, 3H, OH), 6.54 (t, 3H, OH), 6.43 (t,

3H, OH), 4.82 (d, 3H, J = 7.6 Hz, HC₁), 4.64 (m, 2H, CH₂glycine), 4.55

(m, 3H, HC₄), 4.45 (m, 9H, HC₂and HC₆), 4.18 (m, 6H, HC₃and

CH_2a-O-galactosyl), 4.04 (m, 3H, HC₅), 3.90 (m, 3H, CH_2b-O-

galactosyl), 3,64 (m, 18H, 2CH₂O and CH₂NH), 2.67 (m, 6H,

CH₂CO), 2.57 [m, 6H, (CH₂)₃-C], -2.42 (s, 2H, NH). ¹³C NMR

(pyridine-d₅): δ (ppm) 173.8 (CO-den), 169.6 (CO glycine), 168.3

(CO phenyl), 145.2 (C₁carboxyphenyl), 142.2 (C₁phenyl), 134.8 (o-

phenyl and o-carboxyphenyl), 134.3 (p-carboxyphenyl), 131.6 (C pyrrole),

128.2 (p-phenyl), 127.2 (m-phenyl), 126.7 (m-carboxyphenyl), 120.9

(meso-C₁₅), 120.8 (meso-C_10,20), 119.6 (meso-C₅), 105.1 (C₁), 77 (C₅),

75.1 (C₃), 72.3 (C₂), 70.3 (CH₂O), 70.1 (C₄), 70 (CH₂O), 68.7 (CH₂-O-

galactosyl), 62.2 (C₆), 58.7 (C-NH), 44.7 (CH₂glycine), 39.6 (CH₂-NH),

31.3 [(CH₂)₃-C], 30.8 (COCH₂).

Porphyrin 4:³⁵The title compound was deprotected as in com-

pound 1 from peracetylated porphyrin 4-OAc. Product 4 was

obtained as a red powder and used without other purification (yield

92%). HPLC Rt = 13.79 min. MALDI-TOF MS calcd for C₈₁H₉₄N₉O₂₃

(MH^þ) 1560.64, found 1560.68. UV-vis spectrum in MeOH/pyridine

(24/1, v/v): λ_max, nm (ε, L mmol^-1cm^-1) 414 (274.4), 514.5 (12.2),

548 (5.3), 588.5 (3.6), 645.5 (2.4). ¹H NMR (pyridine-d₅): δ (ppm) 10

(broad s, 1H, NH glycine), 9.05 (m, 8H, HC pyrrole), 8.78 (s, 2H, m-

carboxyphenyl), 8.73 (m, 1H, NH-CH₂), 8.42 (s, 2H, o-carboxyphenyl),

8.37 (m, 6H, o-phenyl), 7.81 (m, 9H, m- and p-phenyl), 6.97 (t, 3H,

OH), 6.77 (t, 3H, OH), 6.70 (t, 3H, OH), 6.56 (t, 3H, OH), 5.41 (s, 3H,

HC₁), 4.58 (d, 2H, CH₂glycine), 4.58 (m, 12H, HC_2,3,4,6a), 4.39 (m,

6H, HC_5,6b), 4.12 (m, 3H, HC_2a-O-mannosyl), 3.80 (m, 3H, HC_2b-O-

mannosyl), 3.74 (m, 6H, CH-NH), 2.71 (m, 6H, CH₂-CO), 2.60 [m,

6H, (CH₂)₃-C], -2.41 (s, 2H, NH). ¹³C NMR (pyridine-d₅): δ (ppm)

174 (CO-den), 169.9 (CO glycine), 168.6 (CO carboxyphenyl), 145.4

(C₁carboxyphenyl), 142.4 (C₁phenyl), 135 (o-phenyl and o-

carboxyphenyl), 134.3 (p-carboxyphenyl), 131.7 (C pyrrole), 128.3 (p-

phenyl), 127.3 (m-phenyl), 126.9 (m-carboxyphenyl), 120.9 (meso-

C_10,15,20), 119.8 (meso-C₅), 101.8 (C₁), 75.5 (C₅), 72.8 (C_2,3,4), 72

(C_2,3,4), 69.1 (C_2,3,4), 67.1 (CH₂-O-mannosyl), 63.1 (C₆), 59 (C-NH),

44.9 (CH₂glycine), 39.9 (C-NH), 31.7 [(CH₂)₃-C], 31.2 (COCH₂).

Porphyrin 5: The title compound was deprotected as in compound

1 from peracetylated porphyrin 5-OAc. Product 5 was obtained as a

red powder and used without other purification (yield 94%). HPLC

Rt = 13.55 min. MALDI-TOF MS calcd for C₈₇H₁₀₆N₉O₂₆(MH^þ)

1692.72, found 1692.72. UV-vis spectrum in MeOH/pyridine (24/1,

v/v): λ_max, nm (ε, L mmol^-1cm^-1) 414 (298.5), 513 (12.4), 546

Porphyrin 7:³⁵The title compound was deprotected as in com-

pound 1 from peracetylated porphyrin 7-OAc. Pure title com-

pound was obtained as a red powder and used without other purification

(yield 95%). HPLC Rt = 13.73 min. MALDI-TOF MS calcd for

C₈₇H₁₀₆N₉O₂₆(MH^þ) 1692.71, found 1692.78. UV-vis spectrum in

MeOH/pyridine (24/1, v/v): λ_max, nm (ε, L mmol^-1cm^-1) 414

(347), 513 (14.2), 546.5 (6.4), 589 (4.3), 644.5 (3.1). ¹H NMR

(pyridine-d₅): δ (ppm) 9.88 (t, 1H, J = 5.1 Hz, NH glycine), 9.08 (d,

2H, J = 4.4 Hz, HC_3,7), 9.03 (s, 6H, HC_12,13,17,18), 9.02 (d, 2H, HC_2,8),

8.76 (d, 2H, J = 8 Hz, m-carboxyphenyl), 8.64 (broad s, 1H, NH-CH₂),

8.58 (broad s, 3H, NH-CH₂), 8.40 (m, 6H, o-carboxyphenyl), 8.36 (m,

2H, o-phenyl), 7.80 (m, 9H, m- and p-phenyl), 5.39 (s, 3H, HC₁), 4.61

(m, 3H, CH₂), 4.55 (m, 12H, C_2,3,4,6), 4.36 (m, 6H, HC₅), 4.36 (d, 3H,

J = 8.4 Hz, H_aC₆), 4.06 (m, 3H, CH_2a-O-mannosyl), 3.72 (m, 3H, CH_2b-

O-mannosyl), 3.63 (m, 14H, CH₂), 2.70 [s, 6H, (CH₂)₃-C], 2.58 (broad

s, 6H, CH₂CO), -2.44 (s, 2H, NH). ¹³C NMR (pyridine-d₅): δ (ppm)

173.9 (CO-den), 169.7 (CO glycine), 168.4 (CO-phenyl), 145.4 (C₁

carboxyphenyl), 142.4 (C₁phenyl), 135 (o-carboxyphenyl and o-

phenyl), 134.5 (p-carboxyphenyl), 131.8 (C pyrrole), 128.3 (p-phenyl),

127.4 (m-phenyl), 126.9 (m-carboxyphenyl), 121 (meso-C₁₅), 120.9

(meso-C_10,20), 119.8 (meso-C₅), 101.6 (C₁), 75.3 (C₅), 72.9 (C_2,3,4), 72

(C_2,3,4), 70.4 (CH₂-O-mannosyl), 70.2 (CH₂), 69.2 (C_2,3,4), 66.8 (CH₂-

O-mannosyl), 63.3 (C₆), 58.8 (C-NH), 44.8 (CH₂glycine), 40 (CH₂-

NH), 31.5 [(CH₂)₃-C], 31 (COCH₂).

₁3

(5.5), 589 (3.7), 644.5 (2.7). H NMR (pyridine-d₅): δ (ppm) 9.95

(broad s, 1H, NH glycine), 9.05 (d, 2H, J = 4.7 Hz, HC_3,7pyrrole), 9.03

(m, 6H, HC_{2,8,12,13,17,18}pyrrole), 8.76 (d, 2H, J = 7.7 Hz, m-

carboxyphenyl), 8.61 (broad t, 3H, NH-CH₂), 8.38 (m, 8H, o-phenyl

and o-carboxyphenyl), 7.8 (m, 9H, m- and p-phenyl), 7.37 (t, 3H, OH),

7.16 (m, 6H, 2OH), 6.48 (t, 3H, OH), 4.91 (d, 3H, J = 7.3 Hz, HC₁),

4.63 (m, 2H, CH₂glycine), 4.49 (m, 3H, H_aC₆), 4.32 (m, 3H, H_bC₆),

4.19 (m, 9H, HC₃, HC₄and CH_2a-O-glucosyl), 4.02 (m, 3H, HC₂), 3.88

(m, 6H, HC₅and CH_2b-O-glucosyl), 3.64 (m, 18H, CH₂NH and

2CH₂O), 2.65 (m, 6H, CH₂CO), 2.58 [m, 6H, (CH₂)₃-C], -2.44 (s,

2H, NH). ¹³C NMR (pyridine-d₅): δ (ppm) 173.8 (CO-den), 168.6

(CO glycine), 168.4 (CO phenyl), 145.2 (C₁carboxyphenyl), 142.2 (C₁

phenyl), 134.7 (o-phenyl and o-carboxyphenyl), 134.3 (p-carboxyphenyl),

131.4 (C pyrrole), 128.2 (p-phenyl), 127.2 (m-phenyl), 126.7 (m-

carboxyphenyl), 120.9 (meso-C₁₅), 120.8 (meso-C_10,20), 119.6 (meso-C₅),

104.5 (C₁), 78.3 (C₃and C₅), 74.9 (C₂), 71.3 (C₄), 70.3 (CH₂O), 70

(CH₂O), 69.8 (CH₂-O-glucosyl), 62.4 (C₆), 58.6 (C-NH), 44.7 (CH₂

glycine), 39.6 (CH₂-NH), 31.4 [(CH₂)₃-C], 30.8 (COCH₂).

Porphyrin 8: The title compound was deprotected as in compound

1 from peracetylated porphyrin 8-OAc. Pure title compound was

obtained as a red powder powder and used without other purification

(yield 94%). HPLC Rt = 13.74 min. MALDI-TOF MS calcd for

C₉₃H₁₁₉N₉O₂₉(MH^þ) 1825.80, found 1825.82. UV-vis spectrum in

MeOH/pyridine (24/1, v/v): λ_max, nm (ε, L mmol^-1cm^-1) 414

(389.3), 513 (15.9), 546 (7.2), 589 (4.9), 645 (3.5). ¹H NMR

(pyridine-d₅): δ (ppm) 9.97 (t, 1H, J = 5.2 Hz, NH glycine), 9.07 (d,

2H, J = 4.8 Hz, HC_3,7pyrrole), 9.02 (s, 4H, HC_{2,8,12,13,17,18}pyrrole),

8.75 (d, 2H, J = 8.1 Hz, m-carboxyphenyl), 8.64 (broad s, 1H, NH), 8.60

(broad t, 1H, NH-CH₂), 8.41 (d, 2H, J = 8.1 Hz, o-carboxyphenyl), 8.35

(m, 6H, o-phenyl), 7.79 (m, 6H, m- and p-phenyl), 6.97 (t, 6H, 2OH),

6.67 (t, 3H, OH), 6.27 (t, 3H, OH), 5.40 (d, 3H, J = 1.2 Hz, HC₁), 4.62

(m, 3H, HC_2,3,4,5), 4.60 (s, 2H, CH₂glycine), 4.55 (m, 3H, H_aC₆), 4.55

(dd, 3H, J = 3.1 and 10.1 Hz, HC_2,3,4,5), 4.55 (d, 3H, J = 10 Hz,

HC_2,3,4,5), 4.36 (d, 6H, J = 6 and 13.6 Hz, H_bC₆), 4.34 (m, 3H,

HC_2,3,4,5), 4.05 (m, 3H, CH_2a-O-mannosyl), 3.72 (m, 3H, CH_2b-O-

mannosyl), 3.64 (m, 18H, CH₂-NH and CH₂), 3.57 (m, 12H, CH₂-O),

Porphyrin 6: The title compound was deprotected as in compound

1 from peracetylated porphyrin 6-OAc. Product 6 was obtained as a

red powder and used without other purification (yield 94%). HPLC

2025

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

2.66 (m, 6H, CH₂-CO), 2.56 (m, 6H, (CH₂)₃-C), -2.43 (s, 2H, NH).

¹³C NMR (pyridine-d₅): δ (ppm) 173.8 (CO-den), 169.6 (CO glycine),

168.5 (CO carboxyphenyl), 145.4 (C₁carboxyphenyl), 142.3 (C₁

phenyl), 135 (o-phenyl and o-carboxyphenyl), 134.6 (p-carboxyphenyl),

131.8 (C pyrrole), 128.4 (p-phenyl), 127.4 (m-phenyl), 126.9 (m-

carboxyphenyl), 121.1 (meso-C₁₅), 121 (meso-C_10,20), 119.8 (meso-

C₅), 101.8 (C₁), 75.3 (C_2,3,4,5), 73 (C_2,3,4,5), 72.2 (C_2,3,4,5), 70.8

(CH₂-O), 70.6 (CH₂-O), 70.4 (CH₂-O), 69.2 (C_2,3,4,5), 66.8 (CH₂-

O-mannosyl), 63.2 (C₆), 58.8 (C-NH), 45 (CH₂glycine), 40 (C-NH),

31.6 [(CH₂)₃-C], 31 (COCH₂).

126.8 (m-carboxyphenyl), 120.8 (meso-C₁₅), 120.7 (meso-C_10,20), 119.6

(meso-C₅), 105.2 (C₁), 76.8 (C₅), 75 (C₃), 72.4 (C₂), 70 (C₄), 69.2

(CH₂-O-galactosyl), 62.3 (C₆), 58.8 (C-NH), 57 (CH phenylalanine),

40.2 (CH₂-NH), 38.5 (CH₂phenylalanine), 31.3 [(CH₂)₃-C], 30.8

(COCH₂).

Porphyrin 11: The title compound was deprotected as in com-

pound 1 from peracetylated porphyrin 11-OAc. Pure title compound

was obtained after drying as a red powder and used without other

purification (yield 80%). HPLC Rt = 15.75 min. MALDI-TOF MS calcd

for C₈₈H₁₀₀N₉O₂₃(MH^þ) 1650.69, found 1650.66. Anal. (C₈₈H₉₉-

N₉O₂₃), 8H₂O calcd: C 58.89, H 6.46, N 7.02. Found: C 58.75; H 6.22;

N 6.87. UV-vis spectrum in MeOH/pyridine (24/1, v/v): λ_max, nm

(ε, L mmol^-1cm^-1) 414 (380.4), 512.5 (15.4), 547 (6.7), 588.5 (4.5),

Porphyrin 9: The title compound was deprotected as in compound

1 from peracetylated porphyrin 9-OAc. Pure title compound was

obtained as a red powder and used without other purification (yield

644.5 (3). ¹H NMR (pyridine-d₅): δ (ppm) 9.78 (d, 1H, NH

phenylalanine), 9.06 (d, 2H, J = 4.8 Hz, HC_3,7pyrrole), 9.02 (s, 4H,

HC_12,13,17,18pyrrole), 8.98 (d, 2H, J = 4.8 Hz, HC_2,8pyrrole), 8.63 (d,

2H, J = 8.2 Hz, m-carboxyphenyl), 8.52 (m, 3H, NH-CH₂), 8.36 (m, 6H,

o-phenyl), 8.33 (m, 2H, o-carboxyphenyl), 7.79 (m, 9H, m- and p-

phenyl), 7.51 (d, 2H, J = 7.0 Hz, o-phenylalanine), 7.37 (t, 2H, J = 7.6 Hz,

m-phenylalanine), 7.29 (d, 1H, J = 7.3 Hz, p-phenylalanine), 6.91 (t, 3H,

OH), 6.71 (t, 3H, OH), 6.64 (t, 3H, OH), 6.46 (t, 3H, OH), 5.49 (dd,

1H, J = 7.9 Hz, HC phenylalanine), 5.37 (m, 3H, HC₁), 4.56 (m, 12H,

HC₂, HC₃, HC₄and H_aC₆), 4.35 (m, 6H, HC₅and H_bC₆), 4.08 (m, 3H,

CH_2a-O-mannosyl), 3.80 [m, 3H, CH_2b-O-mannosyl), 3.71 (m, 6H,

CH₂NH), 3.55 (m, 2H, CH₂phenylalanine), 2.56 [m, 12H, CH₂CO

and (CH₂)₃-C], -2.45 (s, 2H, NH). ¹³C NMR (pyridine-d₅): δ (ppm)

173.8 (CO-den), 172.2 (CO phenylalanine), 168.8 (CO phenyl), 145.2

(C₁carboxyphenyl), 142.2 (C₁phenyl), 138.3 (C₁phenylalanine), 134.8

(o-carboxyphenyl), 134.7 (o-phenyl), 134.2 (p-carboxyphenyl), 131.7 (C

pyrrole), 129.9 (o-phenylalanine), 128.8 (m-phenylalanine), 128.2 (m- and

p-phenyl), 127.2 (p-phenylalanine), 126.9 (m-carboxyphenyl), 120.8 (meso-

C₁₅), 120.7 (meso-C_10,20), 119.6 (meso-C₅), 101.6 (C₁), 75.3 (C₅), 72.7

(C₃), 71.9 (C₂), 69 (C₄), 67 (CH₂-O-mannosyl), 62.9 (C₆), 58.9 (C-NH),

57.4 (CH phenylalanine), 39.8 (CH₂-NH), 38.4 (CH₂phenyl-

alanine), 31.4 (COCH₂), 31 [(CH₂)₃-C].

88%). HPLC Rt = 15.20 min. MALDI-TOF MS calcd for C₈₈H₁₀₀

N₉O₂₃(MH^þ) 1650.69, found 1650.75. UV-vis spectrum in MeOH/

pyridine (24/1, v/v): λ_max, nm (ε, L mmol^-1cm^-1) 414 (322.9), 513

₁3

(13.1), 547 (5.8), 588.5 (3.8), 644.5 (2.7). H NMR (pyridine-d₅): δ

(ppm) 9.82 (d, 1H, J = 7.68 Hz, NH phenylalanine), 9.06 (d, 2H, J = 4.7

Hz, HC_3,7pyrrole), 9.03 (s, 4H, HC_12,13,17,18pyrrole), 8.93 (d, 2H, J =

4.7 Hz, HC_2,8pyrrole), 8.63 (d, 2H, J = 8.0 Hz, m-carboxyphenyl), 8.43

(broad t, 3H, NH-CH₂), 8.36 (m, 6H, o-phenyl), 8.34 (m, 2H,

o-carboxyphenyl), 7.8 (m, 9H, m- and p-phenyl), 7.53 (d, 2H, J = 7.2 Hz,

o-phenylalanine), 7.39 (t, 2H, m-phenylalanine), 7.26 (m, 1H,

p-phenylalanine), 7.25 (m, 6H, 2OH), 7.17 (t, 3H, OH), 6.52 (t, 3H,

OH), 5.56 (dd, 1H, J = 6.7 Hz, HC phenylalanine), 4.88 (d, 3H, J = 7.6

Hz, HC₁), 4.57 (m, 3H, H_aC₆), 4.34 (m, 3H, H_bC₆), 4.22 (m, 6H, HC₃

and HC₄), 4.17 (m, 3H, CH_2a-O-glucosyl), 4.05 (m, 3H, HC₂), 3.98 (m,

6H, HC₅and CH_2b-O-glucosyl), 3.73 (m, 6H, CH₂NH), 3.63 (m, 1H,

CH_2aphenylalanine), 3.51 (m, 1H, CH_2bphenylalanine), 2.57 [broad s,

6H, (CH₂)₃-C], 2.51 (broad s, 6H, CH₂CO), -2.44 (s, 2H, NH). ¹³

NMR (pyridine-d₅):δ(ppm) 173.7 (CO-den), 172.1 (CO phenylalanine),

168.7 (CO phenyl), 145.3 (C₁carboxyphenyl), 142.3 (C₁phenyl), 139.1

(C₁phenylalanine), 134.9 (o-carboxyphenyl and o-phenyl), 134.7 (p-

carboxyphenyl), 131.5 (C pyrrole), 129.9 (o-phenylalanine), 128.8 (m-

phenylalanine), 128.2 (m- and p-phenyl), 127.2 (p-phenylalanine), 126.9

(m-carboxyphenyl), 121 (meso-C₁₅), 120.8 (meso-C_10,20), 119.6 (meso-C₅),

104.9 (C₁), 78.4 (C₃), 78.3 (C₅), 75.1 (C₂), 71.5 (C₄), 69.5 (CH₂-O-

glucosyl), 62.6 (C₆), 59 (C-NH), 57.2 (CH phenylalanine), 40.3 (CH₂-

NH), 38.5 (CH₂phenylalanine), 31.5 [(CH₂)₃-C], 30.9 (COCH₂).

Porphyrin 10: The title compound was deprotected as in com-

pound 1 from peracetylated porphyrin 10-OAc. Pure product 10

(yield 92%) was obtained as a red powder and used without other

purification. HPLC Rt = 15.21 min. MALDI-TOF MS calcd for

C₈₈H₁₀₀N₉O₂₃(MH^þ) 1650.69, found 1650.67. UV-vis spectrum in

MeOH/pyridine (24/1, v/v): λ_max, nm (ε, L mmol^-1cm^-1) 414

Porphyrin 12: The title compound was deprotected as in com-

pound 1 from peracetylated porphyrin 12-OAc. Pure title compound

was obtained after drying as a red powder and used without other

purification (yield 96%). HPLC Rt = 15.18 min. MALDI-TOF MS calcd

for C₉₄H₁₁₂N₉O₂₆(MH^þ) 1782.76, found 1782.77. UV-vis spectrum

in MeOH/pyridine (24/1, v/v): λ_max, nm (ε, L mmol^-1cm^-1) 414

(265), 513 (10.8), 546 (4.7), 589 (3.2), 644 (2.2). ¹H NMR (pyridine-

d₅): δ (ppm) 9.81 (d, 1H, J = 7.4 Hz, NH phenylalanine), 9.07 (d, 2H,

J = 4.7 Hz, HC_3,7pyrrole), 9.03 (s, 4H, HC_12,13,17,18pyrrole), 8.93 (d,

2H, J = 4.8 Hz, HC_2,8pyrrole), 8.84 [broad s, 1H, NH-(C)], 8.60 (d, 2H,

J = 7.9 Hz, m-carboxyphenyl), 8.50 (broad t, 3H, NH-CH₂), 8.33 (m,

8H, o-phenyl and o-carboxyphenyl), 7.8 (m, 9H, m- and p-phenyl), 7.56

(m, 2H, o-phenylalanine), 7.38 (m, 2H, m-phenylalanine), 7.35 (t, 3H,

OH), 7.29 (m, 1H, p-phenylalanine), 7.18 (m, 6H, 2OH), 6.45 (t, 3H,

OH), 5.57 (m, 1H, HC phenylalanine), 4.90 (d, 3H, J = 7.7 Hz, HC₁),

4.48 (m, 3H, H_aC₆), 4.34 (m, 3H, H_bC₆), 4.23 (m, 6H, HC₃and HC₄),

4.16 (m, 3H, CH_2a-O-glucosyl), 4.01 (m, 3H, HC₂), 3.88 (m, 6H, HC₅

and CH_2b-O-glucosyl), 3.59 (m, 20H, CH₂NH, CH₂phenylalanine and

(320.7), 513 (13), 546 (5.8), 589.5 (3.8), 644.5 (2.7). ¹H NMR

(pyridine-d₅): δ (ppm) 9.81 (broad s, 1H, NH phenylalanine), 9.07

(d, 2H, J = 4.5 Hz, HC_3,7pyrrole), 9.03 (s, 4H, HC_12,13,17,18pyrrole),

8.93 (d, 2H, J = 4.6 Hz, HC_2,8pyrrole), 8.64 (d, 2H, J = 7.9 Hz, m-

carboxyphenyl), 8.42 (m, 3H, NH-CH₂), 8.36 (m, 6H, o-phenyl), 8.33

(m, 2H, o-carboxyphenyl), 7.80 (m, 9H, m- and p-phenyl), 7.54 (d, 2H,

J = 6.9 Hz, o-phenylalanine), 7.39 (t, 2H, J = 7.4 Hz, m-phenylalanine),

7.32 (d, 1H, J = 6.9 Hz, p-phenylalanine), 7.05 (t, 3H, OH), 6.83 (t, 3H,

OH), 6.59 (t, 3H, OH), 6.42 (3H, OH), 5.58 (dd, 1H, J = 7.3 Hz, HC

phenylalanine), 4.79 (d, 3H, J = 7.6 Hz, HC₁), 4.44 (m, 12H, HC₂, HC₄

and HC₆), 4.17 (m, 6H, HC₃and CH_2a-O-galactosyl), 4.06 (m, 3H,

HC₅), 3.99 (m, 3H, CH_2b-O-galactosyl), 3.69 (m, 6H, CH₂NH), 3.61

(m, 1H, CH_2aphenylalanine), 3.51 (m, 1H, CH_2bphenylalanine), 2.53

[m, 12H, (CH₂)₃-C and CH₂CO], -2.44 (s, 2H, NH). ¹³C NMR

(pyridine-d₅): δ (ppm) 173.9 (CO-den), 172.1 (CO phenylalanine),

168.6 (CO phenyl), 145.1 (C₁carboxyphenyl), 142.2 (C₁phenyl),

138.3 (C₁phenylalanine), 134.8 (o-carboxyphenyl and o-phenyl), 134.3

(p-carboxyphenyl), 131.5 (C pyrrole), 129.8 (o-phenylalanine), 128.7

(m-phenylalanine), 128.1 (m- and p-phenyl), 127.2 (p-phenylalanine),

2CH₂O), 2.57 [m, 12H, (CH₂)₃-C and CH₂CO], -2.44 (s, 2H, NH). ¹³

NMR (pyridine-d₅): δ (ppm) 173.8 (CO-den), 172 (CO phenylalanine),

168.5 (CO phenyl), 145.2 (C₁carboxyphenyl), 142.2 (C₁phenyl), 138 (C₁

phenylalanine), 134.9 (o-phenyl), 134.7 (o-carboxyphenyl and p-

carboxyphenyl), 131.5 (C pyrrole), 129.9 (o-phenylalanine), 128.7 (m-

phenylalanine), 128.2 (p-phenyl), 127.3 (m-phenyl and p-phenylalanine),

126.9 (m-carboxyphenyl), 120.9 (meso-C₁₅), 120.8 (meso-C_10,20), 119.6

(meso-C₅), 104.6 (C₁), 78.4 (C₃and C₅), 75 (C₂), 71.5 (C₄), 70.4

(CH₂O), 70.1 (CH₂O), 69.7 (CH₂-O-glucosyl), 62.5 (C₆), 58.8 (C-

NH), 57.6 (CH phenylalanine), 39.7 (CH₂-NH), 38.5 (CH₂phenyl-

alanine), 31.3 [(CH₂)₃-C], 30.8 (COCH₂).

2026

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

Porphyrin 13: The title compound was deprotected as in com-

pound 1 from peracetylated porphyrin 13-OAc. Pure title com-

pound was obtained as a red powder and used without other purification

(yield 98%). HPLC Rt = 15.19 min. MALDI-TOF MS calcd for

C₉₄H₁₁₂N₉O₂₆(MH^þ) 1782.76, found 1782.75. UV-vis spectrum in

MeOH/pyridine (24/1, v/v): λ_max, nm (ε, L mmol^-1cm^-1) 414

(441.4), 512.5 (17.7), 547 (7.8), 589.5 (5.2), 644.5 (3.6). H NMR

(pyridin-d₅): δ (ppm) 8.81 (d, 2H, J = 4.8 Hz, HC_3,7pyrrole), 8.77 (d,

2H, J = 4.8 Hz, HC_2,8pyrrole), 8.74 (s, 6H, HC_12,13,17,18pyrrole), 8.71

(broad s, 1H, NH glycyl), 8.32 (d, 2H, J = 8.3 Hz, m-carboxyphenyl), 8.25

(d, 2H, J = 8.2 Hz, o-carboxyphenyl), 8.17 (dd, 2H, J = 1.7 and 7.8 Hz, o-

phenyl), 8.07 (dd, 2H, J = 1.3 and 7.8 Hz, o-phenyl), 7.82 (broad t, 1H, J = 3

Hz, NH), 7.72 (m, 9H, m- and p-phenyl), 7.58 (m, 9H, m- and p-phenyl),

7.52 (broad t, 3H, NH), 4.78 (t, 3H, OH), 4.27 (d, 2H, J = 4.6 Hz, CH₂

glycine), 3.71 (m, 6H, CH₂OH), 3.54 (m, 12H, CH₂-O), 3.43 (m, 6H

CH₂), 2.32 (m, 6H, CH₂-CO), 2.11 (m, 6H, CH₂-C), -2.83 (s, 2H, NH).

¹³C NMR (pyridine-d₅): δ (ppm) 174.3 (CO-den), 169.9 (CO glycine),

168.8 (CO carboxyphenyl), 145.9 (C₁carboxyphenyl), 142 (C₁15-

phenyl), 141.9 (C₁10,20-phenyl), 134.6 (o-carboxyphenyl), 134.5 (15-o-

phenyl), 134.4 (10,20-o-phenyl), 132.6 (p-carboxyphenyl), 131 (C

pyrrole), 128.3 (p-phenyl), 127.6 (p-phenyl), 126.6 (m-phenyl), 125.9

(m-carboxyphenyl), 120.5 (meso-C₁₅), 120.3 (meso-C_10,20), 118.5 (meso-

C₅), 75.5 (CH₂-O), 69.4 (CH₂-O), 61.5 (CH₂OH), 58.9 (C-NH), 44.5

(CH₂glycine), 39.6 (C-NH), 31.1 [(CH₂)₃-C and COCH₂].

(339.5), 512.5 (13.9), 546.5 (6.2), 588.5 (4.1), 644 (2.9). H NMR

(pyridine-d₅): δ (ppm) 9.81 (d, 1H, NH phenylalanine), 9.08 (d, 2H, J =

4.8 Hz, HC_3,7pyrrole), 9.04 (s, 4H, HC_12,13,17,18pyrrole), 8.96 (d, 2H,

J = 4.8 Hz, HC_2,8pyrrole), 8.85 [broad s, 1H, NH-(C)], 8.64 (d, 2H, J =

8.0 Hz, m-carboxyphenyl), 8.51 (broad t, 3H, NH-CH₂), 8.35 (m, 8H, o-

phenyl and o-carboxyphenyl), 7.80 (m, 9H, m- and p-phenyl), 7.58 (m,

2H, o-phenylalanine), 7.38 (m, 2H, m-phenylalanine), 7.28 (m, 1H, p-

phenylalanine), 7.21 (t, 3H, OH), 6.75 (t, 3H, OH), 6.54 (t, 3H, OH),

6.42 (t, 3H, OH), 5.60 (m, 1H, HC phenylalanine), 4.82 (d, 3H, J =

7.6 Hz, HC₁), 4.54 (m, 3H, HC₄), 4.46 (m, 9H, HC₂and HC₆), 4.19 (m,

6H, HC₃and CH_2a-O-galactosyl), 4.04 (m, 3H, HC₅), 3.91 (m, 3H,

CH_2b-O-galactosyl), 3,67 (m, 20H, 2CH₂O, CH₂NH and CH₂

phenylalanine), 2.63 [m, 12H, (CH₂)₃-C and CH₂CO], -2.42 (s,

2H, NH). ¹³C NMR (pyridine-d₅): δ (ppm) 173.8 (CO-den), 171.9

(CO phenylalanine), 168.4 (CO phenyl), 145.1 (C₁carboxyphenyl),

142.2 (C₁phenyl), 138.5 (C₁phenylalanine), 134.7 (o-phenyl), 134.6

(o-carboxyphenyl), 134.5 (p-carboxyphenyl), 131.6 (C pyrrole), 129.8

(o-phenylalanine), 128.7 (m-phenylalanine), 128.2 (p-phenyl), 127.2

(m-phenyl and p-phenylalanine), 126.8 (m-carboxyphenyl), 120.9

(meso-C₁₅), 120.8 (meso-C_10,20), 119.6 (meso-C₅), 105.1 (C₁), 76.8

(C₅), 75.2 (C₃), 72.3 (C₂), 70.4 (CH₂O), 70.1 (C₄), 70 (CH₂O), 68.7

(CH₂-O-galactosyl), 62.2 (C₆), 58.7 (C-NH), 57.1 (CH phenylalanine),

39.7 (CH₂-NH), 38.6 (CH₂phenylalanine), 31.4 [(CH₂)₃-C], 30.9

(COCH₂).

’ ASSOCIATED CONTENT

Supporting Information. General experimental infor-

mation and ¹H and ¹³C NMR spectra of all new compounds.

This material is available free of charge via the Internet at

http://pubs.acs.org.

’ AUTHOR INFORMATION

Corresponding Author

*Email: philippe.maillard@curie.u-psud.fr.

Porphyrin 14: The title compound was deprotected as in com-

pound 1 from peracetylated porphyrin 14-OAc. Pure title compound

was obtained after drying as a red powder and used without other

purification (yield 96%). HPLC Rt = 15.54 min. MALDI-TOF MS calcd

for C₉₄H₁₁₂N₉O₂₆(MH^þ) 1782.76, found 1782.71. UV-vis spectrum

in MeOH/pyridine (24/1, v/v): λ_max, nm (ε, L mmol^-1cm^-1) 414

’ ACKNOWLEDGMENT

The authors acknowledge CNRS, the “Programme Incitatif et

Coopꢀeratif Rꢀetinoblastome” of Institut Curie, and the nonproﬁt

French organization ‘‘Rꢀetinostop’’ (http://www.retinostop.fr)

for their ﬁnancial support, Ms. Marianne Bombled, Institut

Curie, for MS analysis, and Vincent Guꢀerineau for MALDI-

TOF analysis.

(220.7), 513 (10.1), 546 (4.7), 589 (3.2), 645 (2.4). ¹H NMR (pyridine-

d₅): δ (ppm) 9.74 (m, 1H, NH phenylalanine), 9.07 (d, 2H, J = 4.7 Hz,

HC_3,7pyrrole), 9.03 (s, 4H, HC_12,13,17,18pyrrole), 8.94 (d, 2H, J = 4.9 Hz,

HC_2,8pyrrole), 8.82 [m, 1H, NH-(C)], 8.60 (m, 2H, m-carboxyphenyl),

8.43 (m, 3H, NH-CH₂), 8.34 (m, 8H, o-phenyl and o-carboxyphenyl), 7.80

(m, 9H, m- and p-phenyl), 7.54 (m, 2H, o-phenylalanine), 7.37 (m, 2H, m-

phenylalanine), 7.29 (m, 1H, p-phenylalanine), 5.55 (m, 1H, HC

phenylalanine), 5.38 (m, 3H, HC₁), 4.56 (m, 12H, HC₂, HC₃, HC₄and

H_aC₆), 4.35 (m, 6H, HC₅and H_bC₆), 4.06 (m, 3H, CH_2a-O-mannosyl),

3.76 (m, 3H, CH_2b-O-mannosyl), 3.58 (m, 20H, 2CH₂O, CH₂NH and

CH₂phenylalanine), 2.56 [m, 12H, (CH₂)₃-C and CH₂CO], -2.44 (s,

2H, NH). ¹³C NMR (pyridine-d₅): δ (ppm) 173.7 (CO-den), 172 (CO

phenylalanine), 168 (CO phenyl), 145.2 (C₁carboxyphenyl), 142.3 (C₁

phenyl), 138.5 (C₁phenylalanine), 134.8 (o-phenyl), 134.6 (o-carboxy-

phenyl and p-carboxyphenyl), 131.5 (C pyrrole), 129.9 (o-phenylalanine),

128.7 (m-phenylalanine), 128.2 (p-phenyl), 127.2 (m-phenyl and p-

phenylalanine), 126.8 (m-carboxyphenyl), 120.9 (meso-C₁₅), 120.8

(meso-C_10,20), 119.9 (meso-C₅), 101.5 (C₁), 75.2 (C₅), 72.8 (C₃), 71.9

(C₂), 70.2 (CH₂O), 70.1 (CH₂O), 69.1 (C₄), 66.6 (CH₂-O-mannosyl),

63.2 (C₆), 58.8 (C-NH), 57.1 (CH phenylalanine), 39.9 (CH₂-NH), 38.6

(CH₂phenylalanine), 31.1 [(CH₂)₃-C], 30.7 (COCH₂).

’ REFERENCES

(1) (a) Vallinayagam, R.; Schmitt, F.; Barge, J.; Wagniꢁeres, G.; Wenger,

V.; Neier, R.; Juillerat-Jeanneret, L. Bioconj. Chem. 2008, 19, 821–839. (b)

Hirohara, S.; Obata, M.; Alitomo, H.; Sharyo, K.; Ogata, S.-I.; Ohtsuki, C.;

Yano, S.; Ando, T.; Tanihara, M. Biol. Pharm. Bull. 2008, 31, 2265–2272.

Biomol. Chem. 2008, 6, 2173–2181. (d) Zheng, X.; Pandey, R. K. Anti-

cancer Agents Med. Chem. 2008, 8, 241–268.

(2) (a) Zorlu, Y.; Ermeydan, M. A.; Dumoulin, F.; Ahsen, V.; Savoie,

H.; Boyle, R. W. Photochem. Photobiol. Sci. 2009, 8, 312–318. (b) Zheng,

X.; Morgan, J.; Pandey, S. K.; Chen, Y.; Tracy, E.; Baumann, H.; Missert,

J. R.; Batt, C.; Jackson, J.; Bellnier, D. A.; Henderson, B. W.; Pandey,

R. K. J. Med. Chem. 2009, 52, 4306–4318. (c) Soares, A. R. M.; Tomꢀe,

J. P. C.; Neves, M. G. P. M. S.; Tomꢀe, A. C.; Cavaleiro, J. A. S.; Torres, T.

Carbohydr. Res. 2009, 344, 507–510. (d) Mꢀenard, F.; Sol, V.; Ringot, C.;

Granet, R.; Alves, S.; Le Morvan, C.; Queneau, Y.; Ono, N.; Krausz, P.

Bioorg. Biomol. Chem. 2009, 17, 7647–7657. (e) McCarthy, J. R.;

Bhaumik, J.; Merbouh, N.; Weissleder, R. Org. Biomol. Chem. 2009,

7, 3430–3436. (f) Liu, J.-Y.; Lo, P.-C.; Fong, W.-P.; Ng, D. K. P. Org.

Biomol. Chem. 2009, 7, 1583–1591. (g) Iqbal, Z.; Hanack, M.; Ziegler, T.

Tetrahedron Lett. 2009, 50, 873–875. (h) Iqbal, Z.; Lyubimtsev, A.;

Hanack, M.; Ziegler, T. Tetrahedron Let. 2009, 50, 5681–5685. (i)

Hirohara, S.; Obata, M.; Alitomo, H.; Sharyo, K.; Ando, T.; Yano, S.;

Tanihara, M. Bioconj. Chem. 2009, 50, 944–952. (j) Hirohara, S.; Obata,

Porphyrin 15: The title compound was deprotected as in com-

pound 1 from peracetylated porphyrin 15-OAc. Product 15 was

obtained as a red powder and used without other purification (yield

95%). HPLC Rt = 18.49 min. MALDI-TOF MS calcd for C₆₉H₇₆N₉O₁₁

(MH^þ) 1206.56, found 1206.56. Anal. (C₆₉H₇₅N₉O₁₁), 2H₂O calcd: C

66.70, H 6.41, N 10.15. Found: C 66.38, H 6.13, N 10.03. UV-vis spectrum

in MeOH/pyridine (24/1, v/v): λ_max, nm (ε, L mmol^-1cm^-1) 414

2027

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

The Journal of Organic Chemistry

ARTICLE

M.; Alitomo, H.; Sharyo, K.; Ando, T.; Tanihara, M.; Yano, S.

J. Photochem. Photobiol., B 2009, 97, 22–33.

(35) Ballut, S.; Makky, A.; Loock, B.; Michel, J.-Ph.; Maillard, Ph.;

Rosilio, V. Chem. Commun. 2009, 224–226.

(3) (a) Hao, E.; Jensen, T. J.; Vicente, M. G. H. J. Porphyrins

Phthalocyanines 2009, 13, 51–59. (b) Grin, M. A.; Lonin, I. S.; Lakhina,

A. A.; Ol’shanskaya, E. S.; Makarov, A. L.; Sebyakin, Y. L.; Guryeva, L.;

Toukach, P. V.; Kononikhin, A. S.; Kuzminc, V. A.; Mironov, A. F.

J. Porphyrins Phthalocyanines 2009, 13, 336–345. (c) Gomes, A. T. P. C.;

Le~ao, R. A. C.; da Silva, F. C.; Neves, M. G. P. M. S.; Faustinoa, M. A. F.;

Tomꢀe, A. C.; Silva, A. M. S.; Pinheiro, S.; de Souza, M. C. B. V.; Ferreira,

V. F.; Cavaleiro, J. A. S. J. Porphyrins Phthalocyanines 2009, 13, 247–255.

(d) Bakar, M. B.; Oelgem€oller, M.; Senge, M. O Tetrahedron 2009,

65, 7064–7078.

(36) Makky, A.; Michel, J.-Ph.; Kasselouri, A.; Briand, E.; Maillard,

Ph.; Rosilio, V. Langmuir 2010, 26, 12761–12768.

(37) Polidori, A.; Pucci, B.; Zarif, L.; Lacombe, J.-M.; Riess, J. G.;

Pavia, A. A. Chem. Phys. Lipids 1995, 77, 225–251.

(38) Zemplꢀen, G. Ber. Dtsch. Chem. Ges. 1927, 1555–1564.

(39) Suda, Y.; Arano, A.; Fukui, Y.; Koshida, S.; Wakao, M.; Nishimura,

T.; Kusumoto, S.; Sobe, M. Bioconj. Chem. 2006, 17, 1125–1135.

(40) Magnusson, G.; Noori, G.; Dahmꢀen, J.; Frejd, T.; Lave, T. Acta

Chem. Scand. 1981, 35, 213–216.

(41) Dahmꢀen, J.; Frejd, T.; Gr€onberg, G.; Lave, T.; Magnusson, G.;

Noori, G. Carbohydr. Chem. 1993, 116, 303–307.

(42) Sasaki, A.; Murahashi, N.; Yamada, H.; Morikawa, A. Biol. Pharm.

Bull. 1994, 17, 680–685.

(4) Chen, X.; Drain, C. M. Drug Des. Rev. - Online 2004, 1, 215–234.

(5) Cavaleiro, J. A. S.; Tomꢀe, J. P. C.; Faustino, M. A. F. Top.

Heterocycl. Chem. 2007, 7, 179–248.

(6) Zheng, X.; Pandey, R. K. Anti-Cancer Agents Med. Chem. 2008,

(43) Sasaki, A.; Murahashi, N.; Yamada, H.; Morikawa, A. Biol. Pharm.

8, 241–268.

Bull. 1995, 18, 740–746.

(7) Maillard, Ph.; Guerquin-Kern, J.-L.; Momenteau, M.; Gaspard, S.

J. Am. Chem. Soc. 1989, 111, 9125–9126.

(44) Kessel, D. Biochemistry 1977, 16, 3443–3449.

(8) Momenteau, M.; Maillard, Ph.; de Bꢀelinay, M.-A.; Carrez, D.;

Croisy, A. J. Biomed. Opt. 1999, 4, 298–318.

(9) Croisy, A.; Lucas, B.; Maillard, Ph. Actual. Chim. Ther. 2005,

31, 181–244.

(10) Laville, I.; Figueiredo, T.; Loock, B.; Pigaglio, S.; Maillard, Ph.;

Grierson, D. S.; Carrez, D.; Croisy, A.; Blais, J. Bioorg. Med. Chem. 2003,

11, 1643–1652.

(11) Monsigny, M.; Roche, A.-C.; Kieda, C.; Midoux, P.; Obrenovitch,

A. Biochimie 1988, 70, 1633–1649.

(12) Lotan, R.; Raz, A. Ann. N.Y. Acad. Sci. 1988, 551, 385–396.

(13) Laville, I.; Pigaglio, S.; Blais, J.-C.; Doz, F.; Loock, B.; Maillard,

Ph.; Grierson, D. S.; Blais, J. J. Med. Chem. 2006, 49, 2558–2567.

(14) Maillard, Ph.; Loock, B.; Grierson, D. S.; Carrez, D.; Croisy, A.;

Laville, I.; Blais, J.; Doz, F.; Desjardins, L. Photodiagn. Photodyn. Ther.

2007, 4, 261–268.

(15) Lupu, M.; Thomas, C. D.; Maillard, Ph.; Loock, B.; Chauvin, B.;

Aerts, I.; Croisy, A.; Beloir, E.; Volk, A.; Mispelter, J. Photodiagn.

Photodynamic Ther. 2009, 6, 214–220.

(16) Varki, A. Glycobiology 1993, 3, 97–130.

(17) Rudd, P. M.; Elliott, T.; Cresswell, P.; Wilson, I. A.; Dwek, R. A.

Science 2001, 291, 2370–2376.

(18) Wells, L.; Vosseller, K.; Hart, G. W. Science 2001, 291, 2376–2378.

(19) Kiessling, L. L.; Pohl, N. L. Chem. Biol. 1996, 3, 71–77.

(20) Mammen, M.; Choi, S.-K.; Whitesides, G. M. Angew. Chem., Int.

Ed. 1998, 37, 2754–2794.

(21) Kiessling, L. L.; Gestwicki, J. E.; Strong, L. E. Curr. Opin. Chem.

Biol. 2000, 4, 696–703.

(22) Lindhorst, T. K. Top. Curr. Chem. 2001, 218, 201–235.

(23) Monsigny, M.; Mayer, R.; Roche, A.-C. Carbohydr. Lett. 2000,

4, 35–52.

(24) Chabre, Y. M.; Roy, R. Curr. Top. Med. Chem. 2008, 8, 1237–1285.

(25) Wong, S. Y. C. Curr. Opin. Struct. Biol. 1995, 5, 599–604.

(26) Villalonga-Barber, C.; Micha-Screttas, M.; Steele, B. R.;

Georgopoulos, A.; Demetzos, C. Curr. Top. Med. Chem. 2008,

8, 1294–1309.

(27) Roy, R. Curr. Opin. Struct. Biol. 1996, 6, 692–702.

(28) Lindhorst, T. K.; Kieburg, C. Angew. Chem., Int. Ed. Engl. 1996,

35, 1953–1956.

(29) Alper, J. Science 2001, 291, 2338–2343.

(30) Bezouska, K. Rev. Mol. Biotechnol. 2002, 90, 269–290.

(31) Sampathkumar, S.-G.; Yarema, K. J. Chem. Biol. 2005, 12, 5–6.

(32) Sampathkumar, S.-G.; Yarema, K. J. Nanotechnologies the Life

Sciences In Nanomaterials for Cancer Diagnosis; Challa, S. S. R, Ed.;

Kumar, Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany,

2007; Vol. 7, pp 1-47.

(33) Ballardini, R.; Colonna, B.; Gandolﬁ, M. T.; Kalovidouris, S. A.;

Orzel, L.; Raymo, F. M.; Stoddart, J. F. Eur. J. Org. Chem. 2003, 288–294.

(34) Matsuo, T.; Nagai, H.; Hisaeda, Y.; Hayashi, T. Chem. Commun.

2006, 3131.

2028

dx.doi.org/10.1021/jo102185d |J. Org. Chem. 2011, 76, 2010–2028

Products guided by the article

Product name:C₃₉H₅₆N₂O₉

Cas No:1274685-93-6

R&D Labs maybe for 1274685-93-6

Hangzhou Taiyan Trading Co., Ltd(expird)

Contact:+86-13777583958

Address:NO.63, Xingyi Street, Xihu District, Hangzhou, Zhejiang, China
CGeneTech (Suzhou, China) Co., Ltd.

Contact:+86-512-62956962

Address:Room 101，Bld C11,218 Xinghu Rd.,Suzhou industrial Park
Shanghai Mio Chemical Co., Ltd

Contact:0086 21- 64401188-622

Address:16 Floor NO.2 Jiefang Building, No. 4855 Dushi Road, 201100 Shanghai, P.R.China
Chen jie

Contact:027-87677569

Address:Room 2203, yujingmingmen Buidling One, xiongchu Road, wuhan city, hubei province, China
ENERGYCO LTD.

Contact:+86-25-83719363

Address:106-7 Chunnan Rd, Chunxi Town, Gaochun, Nanjing, China

Relevant to this article

Enantioselective cobalt-catalyzed preparation of trifluoromethyl- substituted cyclopropanes

Doi:10.1002/anie.201004269
(2011)
Synthesis, 5-HT_1A and 5-HT_2A receptor affinity and QSAR study of 1-benzhydryl-piperazine derivatives with xanthine moiety at N4

Doi:10.1007/s00044-011-9555-y
(2012)
Well-defined diimine copper(I) complexes as catalysts in click azide-alkyne cycloaddition reactions

Doi:10.3390/molecules18088919
(2013)
A Ruthenium(IV) Oxo Complex that contains a Tertiary Diamine Ligand

Doi:10.1039/DT9900000967
(1990)
A selective transformation of enals into chiral γ-amino alcohols

Doi:10.1021/ol4022029
(2013)
Calcium-responsive paramagnetic CEST agents

Doi:10.1016/j.bmc.2010.07.023
(2011)

Article Doi

A strategy for the targeting of photosensitizers. Synthesis, characterization, and photobiological property of porphyrins bearing glycodendrimeric moieties

DOI: 10.1021/jo102185d

Source and publish data:

Authors:

Article abstract of DOI:10.1021/jo102185d

Full text of DOI:10.1021/jo102185d

Products guided by the article

R&D Labs maybe for 1274685-93-6

Relevant to this article

Hot Product