Synthesis of Oxasmaragdyrin–Amino Acid Conjugates

Article abstract of DOI:10.1002/ejoc.201701090

A series of covalently linked oxasmaragdyrin-amino acid and BF₂-oxasamaragdyrin–amino acid conjugates were synthesized by treating oxasmaragdyrin or its BF₂ complex that contain a benzylhydroxyl group at one of the meso positions with an appropriate fluorenylmethyloxycarbonyl-protected amino acid in CH₂Cl₂ in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide·HCl/hydroxybenzotriazole under basic conditions at room temperature. The conjugates are stable, highly soluble in all organic solvents, and confirmed by HRMS. 1D and 2D NMR spectroscopic techniques were used to characterize the oxasmaragdyrin–amino acid conjugates. Absorption, fluorescence, and electrochemical studies of conjugates indicate that the conjugates strongly absorb and emit in visible-NIR region with decent quantum yields, singlet state lifetimes and are stable under electrochemical conditions. Furthermore, the conjugates showed minimal change in their spectral and electrochemical properties relative to that of the unconjugated oxasmaragdyrin or its BF₂ complex suggest that the characteristic features of the oxasmaragdyrin and its BF₂ complex is retained in the conjugates, which will be a useful feature for Near-IR fluorescence imaging and other applications.

Full text of DOI:10.1002/ejoc.201701090

A Journal of
Accepted Article
Title: Synthesis of Oxasmaragdyrin-Amino Acid Conjugates
Authors: KANDALA LAXMAN and Mangalampalli Ravikanth
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European Journal of Organic Chemistry
10.1002/ejoc.201701090
Synthesis of Oxasmaragdyrin-Amino Acid Conjugates
Kandala Laxman[a,b] and Mangalampalli Ravikanth*[a]
aDepartment of Chemistry, Indian Institute of Technology, Bombay, Powai, Mumbai
4
00 076, India. E-mail: ravikanth@chem.iitb.ac.in
b
IITB-Monash Research Academy, IIT Bombay, Powai, Mumbai-400 076, India.
Abstract:
A series of covalently linked oxasmaragdyrin-amino acid and BF
oxasamaragdyrin-amino acid conjugates were synthesized by treating oxasmaragdyrin or
its BF complex containing benzylhydroxyl group at one of the meso position with
appropriate Fmoc-protected amino acid in CH Cl in the presence of EDC.HCl/HOBT under
2
-
2
2
2
basic conditions at room temperature. The conjugates are stable, highly soluble in all
organic solvents and confirmed by HR mass spectrometry. 1D and 2D NMR techniques
were used to characterize the oxasmaragdyrin-amino acid conjuagtes. Absorption,
fluorescence and electrochemical studies of conjugates indicated that the conjugates
strongly absorb and emit in visible-NIR region with decent quantum yields, singlet state
lifetimes and are stable under electrochemical conditions. Furthermore, the conjugates
showed minimal change in their spectral and electrochemical properties compared to that
of the unconjugated oxasmaragdyrin or its BF
2
complex suggesting that the characteristic
features of the oxasmaragdyrin and its BF complex is retained in the conjugates which
2
will be useful feature for Near-IR fluorescence imaging and other applications.
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European Journal of Organic Chemistry
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Introduction
Smaragdyrins I are 22π aromatic expanded pentapyrrolic macrocycles in which
the five pyrroles are connected via three meso-carbons and two direct pyrrole-pyrrole
bonds.[1] Because of the presence of two direct pyrrole-pyrrole bonds, the smaragdyrin
macrocycle is highly strained and not stable for further studies. Thus, to the best of our
knowledge, there are no reports available on synthesis of stable smaragdyrin macrocycles
containing five pyrrole rings. However, Chandrashekar and co-workers reported few
years back the synthesis of meso-triaryl 25-oxasmaragdyrins II which are stable and
exhibit interesting spectral and electrochemical properties.[2] The 25-oxasmaragdyrins
were resulted by replacing one of the pyrrole group of smaragdyrin with furan ring and
these macrocycles absorb and emit in 400-800 nm region with decent quantum yields and
singlet state lifetimes.
The spectral and electrochemical properties of 25-
-complexation of 25-oxasmaragdyrins.[3]
oxasamaragdyrins were further enhanced by BF
2
For example, the BF
times more intense than the absorption band of free base 25-oxasmaragdyrin and also the
BF -smaragdyrins are more fluorescent than free base smaragdyrins with decent quantum
yields and singlet state lifetimes. Thus, 25-oxasmaragdyrins and their BF -complexes are
2
-oxasmargdyrins III showed a strong band at 710 nm that is three
2
2
fluorescent expanded porphyrinoids unlike many other reported expanded porphyrinoids
which are generally non-fluorescent.[4]
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European Journal of Organic Chemistry
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Chart 1: Structures of smaragdyrin analogues
Porphyrins, corroles and their peptide conjugates were previously used in various
applications such as cellular imaging, PDT agents,[5] DSSC due to their photophysical
properties. As these molecules are fluorescent in the visible region, the signal to noise
ratio of fluorescent signal in case of mammalian cells is very less due to auto
fluorescence and scattering. It is known that the mammalian cells are quite transparent in
the region of 650 nm to 900 nm. Therefore, the dyes in this region are very useful for
Near Infrared Fluorescence Imaging (NIRF). Thus, there is a need for the dyes that can
be easily prepared and absorbs and emits strongly in NIR region. However, to best of our
knowledge, there are only handful of dyes which are fluorescent in this region like
cyanine dyes,[7] squaraine dyes,[8] BODIPY analogues,[9] benzo[c]heterocycles,[10]
xanthenes,[11] phthalocyanines and few porphyrin derivatives.[12] Although extensive
literature is presently available on porphyrin-amino acid/peptide/protein conjugates,[13]
only limited reports on contracted porphyrinoids such as corrole-amino acid
conjugates,[14] and very few reports on expanded porphyrins[15] where the expanded
porphyrins were linked to amino acids, peptides and proteins to form covalent conjugates
which can be used for biological applications. We thought of using the fluorescent
[6]
oxasmaragdyrins and their BF complexes to link covalently with various amino acids to
2
synthesize conjugates which can be used for NIR fluorescence imaging studies and other
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European Journal of Organic Chemistry
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applications. With this idea in mind, we attempted to synthesize oxasmaragdyrin/BF -
2
smaragdyrin-amino acid conjugates using readily available precursors under simple
reaction conditions. Herein, we report the synthesis of first examples of covalently linked
meso-triaryl 25-oxasmaragdyrin-amino acid conjugates 1a-1d and their BF
2
complexes
2
a-2d (Chart 2) and studied their photophysical and electrochemical properties. The
studies indicated that the conjugates absorbs and emits strongly in visible-NIR region
with decent quantum yields and singlet state lifetimes and exhibit reversible oxidation
and reduction under electrochemical redox conditions.
Chart 2: Smaragdyrin-amino acid conjugates and their corresponding BF complexes.
2
Results and Discussion
Synthesis and Characterization
The required meso-(4-hydroxymethyl)phenyl dipyrromethane 3 was synthesized
in two steps starting from commercially available 1,4-terephthalaldehyde as shown in
Scheme 1. The 1,4-terephthalaldehyde was selectively reduced by treating with 0.25
equivalent of NaBH
The 4-(hydroxymethyl)benzaldehyde was reacted with excess of pyrrole in the presence
of catalytic amount of TFA in CH Cl followed by work-up and column chromatographic
4
in CH OH to afford 4-(hydroxymethyl)benzaldehyde in 80% yield.
3
2
2
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European Journal of Organic Chemistry
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purification afforded meso(4-hydroxymethyl)phenyl dipyrromethane as white solid in
0% yield.[16] The other desired 16-oxatripyrrane 4 was synthesized by following the
4
reported procedure.[17] The 25-oxasmaragdyrin 5 containing benzylhydroxyl group at
one of the meso position was synthesized by condensing one equivalent of
dipyrromethene 3 with one equivalent of 16-oxatripyrrane 4 in CH
2
Cl in the presence of
2
catalytic amount of TFA for 1 h under inert atmosphere followed by oxidation with DDQ
in open air for additional 1 h. The formation of the 25-oxasmaragdyrin 5 was followed
by tlc analysis and absorption spectroscopy. The crude compound was purified by basic
alumina column chromatography and afforded the desired functionalized 25-
oxasmaragdyrin 5 in 25% yield. The formation of 25-oxasmaragdyrin 5 was confirmed
by HR-MS and NMR spectroscopy. The compound 5 was treated with excess BF
in CH Cl in the presence of triethylamine for 15 min and purified the crude compound
by basic alumina column chromatography to afford pure BF complex of functionalized
5-oxasmaragdyrin 6 as green crystalline solid in 80% yield. The BF -smaragdyrin
3
·OEt
2
2
2
2
2
2
1
19
11
complex 6 was confirmed by HR-MS, H, F and B NMR spectroscopy.
Scheme1: Synthesis oxasmaragdyrin 5.
The smaragdyrin-amino acid 1 as well as BF
2
smaragdyrin-amino acid 2
conjugates were synthesized as shown in the Scheme 2. The oxasmaragdyrin 5 or its BF
2
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European Journal of Organic Chemistry
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complex 6 was reacted with appropriate Fmoc (Fluorenylmethyloxycarbonyl)-protected
amino acid in CH Cl in the presence of 1 equivalent of EDC.HCl (1-Ethyl-3-(3-
dimethylaminopropyl)carbodiimide Hydrochloride), 0.1 equivalent HOBt
Hydroxybenzotriazole) and 1 equivalent DIEA (diisopropylethylamine) at room
2
2
(
temperature for 3 h. The tlc analysis showed the disappearance of the more polar spot
corresponding to the starting material 5 or 6 and appearance of less polar spot
corresponding to the desired conjugate. The crude mixture after standard work-up was
purified by silica gel column chromatography and afforded the desired smaragdyrin-
amino acid conjugates in 25% yields and BF smaragdyrin-amino acid conjugates in 30%
2
yields. The conjugates 1 and 2 are freely soluble in all common organic solvents and
their identities were confirmed by corresponding molecular ion peak in HR-MS.
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European Journal of Organic Chemistry
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Scheme2: Synthesis of oxasmaragdyrin-amino acid conjugates 1a-d and BF
2
complex of
oxasmaragdyrin-amino acid conjugates 2a-d.
The conjuagates 1 and 2 were characterized in detail by 1D and 2D NMR
spectroscopy, absorption, fluorescence and electrochemical techniques. The
1
1
1
representative H NMR and H- H COSY spectra of 2c are presented in Figure 1. In
general, covalently linked smaragdyrin-amino acid conjugates showed five sets of
resonances for 10 protons corresponding to eight pyrrole and two furan protons in the
region of 9 – 10.5 ppm which were identified by their location, integration, coupling
constant and cross-peak connectivity in COSY NMR. The protons corresponding to
amino acid moiety appeared in the region of 1.5 – 6 ppm which were also easily
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European Journal of Organic Chemistry
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identified based on their cross peak correlations in COSY spectra. The inner NH protons
of BF smaragdyrin-amino acid conjugates 2 were appeared at upfield region of -3.5 ppm
which were not observed in smaragdyrin-amino acid conjugates due to their involvement
2
1
9
11
in rapid tautomerism. The conjugates 2 were also characterized by F and B NMR
spectroscopy.
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European Journal of Organic Chemistry
10.1002/ejoc.201701090
1
11
19
1
1
Figure 1: (a) H, (b) B, (c) F, (d) H- H COSY NMR of 2c recorded in CDCl
3
.
The absorption, fluorescence and electrochemical properties of free base/BF -
2
smaragdyrin-amino acid conjugates 1/2 were studied. The comparison of absorption
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European Journal of Organic Chemistry
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spectra of smaragdyrin-phenylalanine conjugate 1c with meso-triaryl smaragdyrin 5 is
presented in Figure 2a and comparison of their corresponding BF - complexes is
2
presented in Figure 2b. As clear from Figures 2a & 2b, the conjugates showed similar
absorption features like smaragdyrin precursors 5 & 6 with almost no shifts in their peak
maxima. However, the extinction coefficients of absorption bands of conjugates were
slightly altered compared to corresponding precursors 5 & 6.
Figure 2: (a) Comparison of absorption and fluorescence (inset) spectra of 1c and 5
recorded in CHCl
3
; (b) Comparison of absorption and fluorescence (inset) spectra of 2c
; (c) Comparison of cyclic Voltammograms and Differential
and 6 recorded in CHCl
3
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European Journal of Organic Chemistry
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Pulse Voltammograms of 2c and 6 in CH
2
Cl containing 0.1M TBAP as supporting
2
electrolyte using scan rate of 50 mV/sec.
The comparison of fluorescence spectra of smaragdyrin and conjugate shown as
an inset in Figure 2a and comparison of fluorescence spectra of BF -smaragdyrin and
conjugate shown as inset in Figure 2b also indicate that the linking of amino acids to
2
smaragdyrin/BF
smaragdyrin/BF
smaragdyrin/BF
2
2
2
-smaragdyrin did not modify the fluorescence properties of
-smaragdyrin moiety supporting weak interaction between the
-smaragdyrin and amiono acid moieties in conjugates.
Table 1: Absorption and fluorescence data of oxasmaragdyrin, BF
2
complexed
oxasmargdyrin and their amino acid conjugates recorded in CHCl3.
Wavelength (nm)
ε in mol L cm x10 )
λ
f
τ
(ns)
Compound
Φ
f
-1
-1
-1
4
(
(nm)
4
47
12.3)
47
8.5)
47
558
(9.2)
558
599
638
700
5
--
714 0.029
714 0.026
--
(
(9.3)
(7.7)
(8.1)
4
599
(5.9)
631
638
(5.9)
649
700
(6.1)
705
1
c
--
--
(
(5.7)
592
4
475
6
714 0.143 4.05
715 0.167 4.10
(
28.4) (12.7) (11.3) (15.5) (18.3) (39.9)
47 475 592 631 649 705
29.9) (12.2) (10.5) (14.8) (17.8) (40.4)
4
2
c
(
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European Journal of Organic Chemistry
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Table 2: Cyclic voltammogram data of oxasmaragdyrin, BF
2
complexed oxasmargdyrin
and their amino acid conjugates recorded in CH
2
Cl
2
containing 0.1M TBAP as
supporting electrolyte using scan rate of 50 mV/sec with BAS electrochemical system
utilizing the three electrode configuration consisting of a glassy carbon (working
electrode), platinum wire (auxillary electrode) and saturated calomel (reference electrode)
electrodes. All potentials were calibrated versus saturated calomel electrode by the
addition of ferrocene as an internal standard, taking E1/2 (Fc/Fc+ ) = 0.42 V vs SCE.
Oxidation
(V)
Reduction
(V)
Compound
I
II
I
II
5
0.49 0.82 -1.32 -1.66
0.46 0.77 -1.27 -1.64
1
c
6
0.73 1.16 -0.97
0.74 1.18 -0.98
--
--
2
c
The electrochemical properties of conjugates 1 and 2 along with their
corresponding precursors were studied in CH Cl by cyclic voltammetry at a scan rate of
0 mV/s using tetrabutylammonium perchlorate (TBAP) as the supporting electrolyte.
The conjugates 1 and 2 also showed two reversible oxidations and one or two
2
2
5
reversible/irreversible reduction(s) like their precursor smaragdyrin 5 and BF -
2
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European Journal of Organic Chemistry
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smaragdyrin 6 with negligible shifts in their peak potentials indicating that the rich redox
chemistry of smaragdyrin/BF -smaragdyrin did not alter significantly by linking them
with various amino acids. Thus, the spectral and electrochemical properties indicate that
the smaragdyrin/BF -smaragdyrin and amino acid moieties did not interact strongly and
2
2
the individual properties of the moieties retained in conjugates.
Conclusions
In summary, we successfully synthesized a series smaragdyrin-amino acid
conjugates and BF -smaragdyrin-amino acid conjugates using readily available building
2
blocks under simple reaction conditions. The conjugates were easily isolated by column
chromatography and characterized in detail by HR-MS, 1D and 2D NMR spectroscopy.
The spectral and electrochemical properties indicated that the conjugates showed similar
rich spectral and redox properties like unconjugated smaragdyrins/BF -smaragdyrins
2
without significant alteration which are very useful for their potential applications as NIR
fluorescent probes in biology and medicine. The biological studies on these conjugates
are currently under investigation in our laboratory.
General Experimental:
All chemicals were used as received unless otherwise noted. All solvents were of at least
reagent grade and dried if necessary. The H, 11B, 19F and 13C NMR spectra were
1
recorded in CDCl
3
on Bruker 400 or 500 MHz instrument. The frequency of 101 and 126
MHz is used for 13C nucleus. Tetramethylsilane [Si(CH
3
4
) ] was used as an internal
1
13
19
standard for H and C NMR, tetrafluorotoluene as an external standard for F NMR
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European Journal of Organic Chemistry
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and boric acid as an external standard for 11B NMR. Absorption and steady state
fluorescence spectra were obtained with Cary series UV-Vis-NIR sectrophotometer and
Varian-Cary Eclipse spectrofluorometer respectively. The fluorescence quantum yield
f
(Φ ) were estimated from emission and absorption spectra by comparative method at the
excitation wavelength of 440 nm using H
2
TTP (Φ
f
= 0.11) as the standard.[18] Cyclic
voltammetric studies were carried out with BAS electrochemical system utilizing the
three electrode configuration consisting of a glassy carbon (working electrode), platinum
wire (auxillary electrode) and saturated calomel (reference electrode) electrodes. The
experiments were done in dry CH
2
Cl
TBAP) as supporting electrolyte. Half wave potentials were measured using DPV
differential pulse voltammetry) and also calculated manually by taking the average of
2
using 0.1 M tetrabutylammonium perchlorate
(
(
the cathodic and anodic peak potentials. All potentials were calibrated versus saturated
calomel electrode by the addition of ferrocene as an internal standard, taking E1/2
+
(
Fc/Fc ) = 0.42 V vs SCE. All the solutions were purged prior to electrochemical and
spectral measurements with argon gas. The high resolution mass spectra (HRMS) were
recorded with a Bruker maxis Impact and Q-Tof micro mass spectrometer. For UV-vis
-3
and fluorescence titrations, the stock solution of all compounds (1×10 M) were prepared
by using HPLC grade chloroform solvent. IR spectra were recorded on a Nicolet Impact-
4
00 FT-IR spectrometer using CsBr plates and analysed.
Synthesis of 4-(hydroxymethyl)benzaldehyde:[15]
To 1,4-terephthalaldehyde (1.0 g, 7.46 mmol) in methanol, sodiumborohydride (70.51
mg, 1.86 mmol) was added at 0 ⁰C and the reaction mixture was stirred at room
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European Journal of Organic Chemistry
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temperature for 3 hours. The completion of the reaction was monitored by the formation
of more polar spot on TLC. After the completion of reaction, the solvent was evaporated
to get crude solid. The crude solid was extracted in dichloromethane and organic layer
was washed with water (3 × 25 mL). The organic layer was dried over anhydrous sodium
sulphate and evaporated to give product as colourless liquid in 80% yield.
Synthesis of compound 3:[15]
To a mixture of 4-(hydroxymethyl) benzaldehyde (1.0 g, 7.34 mmol) and pyrrole (10 mL,
1
46.90 mmol) in dichloromethane under nitrogen atmosphere, TFA (73 µL, 0.73 mmol)
was added. The resulting mixture was stirred for 10 min at room temperature and the
mixture was quenched by 10% aqueous NaOH solution. The organic layer was washed
with water (3 × 50 mL), dried over anhydrous sodium sulphate and evaporated under
reduced pressure to give crude product which was further purified by silica gel column
chromatography (petroleum ether/ethyl acetate) to give pure compound as crystalline
1
solid (0.750 g) in 40% yield. H NMR (500 MHz, Chloroform-d) δ 7.98 (s, 2H), 7.31 (d,
J = 7.9 Hz, 2H), 7.21 (d, J = 8.1 Hz, 2H), 6.68 (d, J = 1.5 Hz, 1H), 6.16 (d, J = 3.0 Hz,
1
3
1
1
H), 5.91 (d, J = 1.0 Hz, 1H), 5.46 (s, 1H), 4.66 (s, 2H). C NMR (126 MHz, CDCl ) δ
3
41.80, 139.64, 132.58, 128.77, 127.53, 117.44, 108.57, 107.37, 65.20, 43.87.
Synthesis of compound 5:
To a mixture of meso-(4-hydroxymethyl)phenyl dipyrromethane 3 (0.310 g, 1.23 mmol),
oxatripyrrane 4 (0.500 g, 1.23 mmol) in dichloromethane solvent, 0.1 equivalents of TFA
(10 µL, 0.123 mmol) was added and stirred at room temperature for 1.5 hours. Then
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European Journal of Organic Chemistry
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DDQ (0.836 g, 3.69 mmol) was added to above mixture and stirred for further 1.5 hours.
The reaction mixture was evaporated under reduced pressure and the crude solid was
subjected to basic-alumina column chromatography using dichloromethane/petroleum
1
ether as solvent to give pure compound as dark green solid in 25% yield. H NMR (400
MHz, Chloroform-d) δ 9.41 (d, J = 4.2 Hz, 2H), 9.34 (d, J = 4.3 Hz, 2H), 8.91 (d, J = 4.3
Hz, 2H), 8.75 (s, 2H), 8.40 (d, J = 4.2 Hz, 2H), 8.33 (d, J = 7.7 Hz, 2H), 8.08 (d, J = 7.8
Hz, 4H), 7.77 – 7.64 (d, J = 7.7 Hz, 2H), 7.60 (d, J = 7.7 Hz, 4H), 4.86 (s, 2H), 2.72 (s,
1
3
6
1
1
2
H). C NMR (126 MHz, CDCl
3
) δ 149.2, 143.7, 139.6, 138.1, 137.8, 136.0, 134.7,
33.8, 131.0, 129.9, 129.3, 128.9, 128.5, 128.3, 127.9, 126.5, 126.3, 126.0, 125.2, 124.4,
-1
19.5, 118.6, 117.7, 115.5, 108.2, 105.5, 65.1, 21.7. IR (ν cm , CHCl
3
) 3393, 2918,
861, 1715, 1600, 1512, 1463, 1463, 1271, 1044, 785, 756. UV/Vis (Chloroform)
-1
3
-1
(
λmax/nm, ε mol dm cm ) 447 (123600), 558 (9200), 599 (8321), 638 (7708), 700
(
8177). Fluorescence (in chloroform) λ
f
(Φ ) 714 nm (0.029) Calculated mass: m/z =
f
6
51.2755, measured mass: m/z = 651.2756 [M+H]+.
Synthesis of compound 1:
To the mixture of (4-(methylhydroxy)phenyl) oxasmaragdyrin 5 (50 mg, 0.077 mmol)
and N-Fmoc protected amino acid (0.23 mmol) in dry CH Cl , diisopropylethylamine (
0 µL, 0.346 mmol) and HOBT (37.4 mg, 0.277 mmol) were added under nitrogen
2
2
6
atmosphere, followed by addition of EDC.HCl (54 mg, 0.277 mmol) at 0 ⁰C. The mixture
was stirred for 12 hr. The reaction was monitored by thin layer chromatography which
showed formation of less polar spot. Upon completion of reaction, the mixture was
washed with 10% NaHCO (3 × 50 mL). The organic layer was collected, dried over
3
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European Journal of Organic Chemistry
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anhydrous Na
product was purified using silica gel column chromatography by EtOAc/Petroleum ether
15%) as eluent to give amino acid conjugate as green solid in 20-25% yield.
2
SO and the solvent was evaporated to give crude product. The crude
4
(
Compound 1a
1
Yield = 22%; H NMR (500 MHz, Chloroform-d) δ 9.51 (d, J = 4.3 Hz, 2H), 9.41 (d, J =
4
7
.3 Hz, 2H), 8.97 (d, J = 4.2 Hz, 2H), 8.81 (s, 2H), 8.50 (d, J = 4.2 Hz, 2H), 8.43 (d, J =
.7 Hz, 2H), 8.12 (d, J = 7.5 Hz, 4H), 7.92 – 7.82 (m, 2H), 7.79 (d, J = 7.5 Hz, 2H), 7.65
(
t, J = 9.1 Hz, 6H), 7.43 (t, J = 7.4 Hz, 2H), 7.36 (td, J = 7.4, 1.2 Hz, 2H), 5.58 (s, 2H),
.41 (s, 1H), 4.44 (d, J = 7.1 Hz, 2H), 4.30 (d, J = 7.3 Hz, 1H), 4.20 (d, J = 5.5 Hz, 2H),
5
2
1
6
1
1
3
.76 (s, 6H). C NMR (101 MHz, CDCl
3
) δ 170.29, 149.2, 143.9, 141.4, 139.6, 137.9,
35.9, 134.8, 133.8, 128.6, 127.9, 127.2, 125.2, 124.4, 120.1, 119.7, 118.8, 115.7, 105.5,
-1
7.4, 67.3, 60.5, 47.2, 43.0, 21.8. IR (ν cm , CHCl
3
) 2925, 2854, 2111, 1664, 1512,
-1
3
-
451, 1273, 1217, 1186, 1054, 782, 758. UV/Vis (Chloroform) (λmax/nm, ε mol dm cm
1)
447 (71900), 558 (5300), 599 (5251), 638 (5066), 700 (5363). Fluorescence (in
chloroform) λ
f
(Φ ) 714 nm (0.015) Calculated mass: m/z = 929.3572, measured mass:
f
m/z = 929.3579 [M+H]+.
Compound 1b
1
Yield = 24%; H NMR (500 MHz, Chloroform-d) δ 9.66 (d, J = 4.3 Hz, 2H), 9.54 (d, J =
4
8
7
.4 Hz, 2H), 9.15 (s, 2H), 9.09 (s, 2H), 8.67 (d, J = 4.2 Hz, 2H), 8.56 (d, J = 7.6 Hz, 2H),
.22 (s, 4H), 7.92 (d, J = 7.5 Hz, 2H), 7.77 (d, J = 7.5 Hz, 2H), 7.67 (d, J = 7.6 Hz, 4H),
.58 (d, J = 7.4 Hz, 2H), 7.41 (t, J = 7.4 Hz, 3H), 7.35 (t, J = 7.5 Hz, 2H), 5.62 (s, 2H),
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European Journal of Organic Chemistry
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5
1
1
1
2
.51 (d, J = 7.9 Hz, 2H), 4.66 (s, 1H), 4.47 (t, J = 7.8 Hz, 2H), 4.30 (s, 1H), 2.78 (s, 6H),
1
3
.66 (d, J = 7.3 Hz, 3H). C NMR (101 MHz, CDCl
3
) δ 170.1, 156.2, 149.0, 143.7,
41.3, 139.4, 137.7, 135.7, 134.6, 133.6, 130.8, 130.3, 129.6, 128.4, 127.7, 127.1, 125.0,
-1
24.2, 119.9, 119.6, 118.6, 115.5, 105.3, 67.3, 47.0, 42.8, 29.7, 21.6. IR (ν cm , CHCl
3
)
925, 2850, 1718, 1601, 1510, 1451, 1271, 1053, 787, 758, 737. UV/Vis (Chloroform)
-1
3
-1
(λ
max/nm, ε mol dm cm ) 447 (71900), 558 (5300), 599 (5251), 638 (5066), 700 (5363).
Fluorescence (in chloroform) λ (Φ ) 714 nm (0.015). Calculated mass: m/z = 944.3806,
f
f
measured mass: m/z = 944.3802 [M+H]+.
Compound 1c
1
Yield = 25%; H NMR (500 MHz, Chloroform-d) δ 9.51 (d, J = 4.3 Hz, 2H), 9.41 (d, J =
4
7
.3 Hz, 2H), 8.97 (d, J = 4.2 Hz, 2H), 8.81 (s, 2H), 8.50 (d, J = 4.2 Hz, 2H), 8.43 (d, J =
.7 Hz, 2H), 8.12 (d, J = 7.5 Hz, 4H), 7.92 – 7.82 (m, 2H), 7.79 (d, J = 7.5 Hz, 2H), 7.65
(
t, J = 9.1 Hz, 6H), 7.41 (dd, J = 7.5, 1.2 Hz, 2H), 7.38 – 7.32 (m, 8H), 7.25 (s, 2H), 5.58
d, J = 5.1 Hz, 2H), 5.45 (d, J = 8.3 Hz, 1H), 4.96 (d, J = 7.3 Hz, 1H), 4.53 (dd, J = 10.7,
(
7
2
1
1
1
7
1
.2 Hz, 1H), 4.45 (dd, J = 10.7, 7.0 Hz, 1H), 4.29 (t, J = 7.0 Hz, 2H), 3.34 (d, J = 5.9 Hz,
1
3
H), 2.80 (s, 6H), -3.81 (d, J = 10.2 Hz, 2H). C NMR (126 MHz, CDCl ) δ 173.9,
3
55.7, 150.8, 144.0, 141.7, 141.3, 140.1, 138.9, 138.1, 136.5, 134.8, 133.2, 132.8, 131.7,
29.4, 128.5, 128.4, 127.7, 127.1, 127.0, 126.8, 126.6, 126.4, 125.3, 125.2, 125.0, 122.3,
20.6, 120.0, 118.2, 117.2, 107.8, 66.8, 65.3, 63.0, 55.0, 52.8, 47.2, 37.7, 29.8, 22.0, 21.8,
-1
.9, 7.8. IR (ν cm , CHCl
3
) 2925, 2854, 1720, 1605, 1512, 1449, 1395, 1274, 1251,
-1
3
-1
053, 912, 793, 761, 739, 700. UV/Vis (Chloroform) (λmax/nm, ε mol dm cm ) 447
(85100), 558 (5700), 599 (5967), 638 (5945), 700 (6164). Fluorescence (in chloroform)
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European Journal of Organic Chemistry
10.1002/ejoc.201701090
λ
f
(Φ
f
) 714 nm (0.026). Calculated mass: m/z = 1020.4119, measured mass: m/z =
1
020.4104 [M+H]+.
Compound 1d
1
Yield = 20%; H NMR (500 MHz, Chloroform-d) δ 9.51 (d, J = 4.3 Hz, 2H), 9.41 (d, J =
4
7
.3 Hz, 2H), 8.97 (d, J = 4.2 Hz, 2H), 8.81 (s, 2H), 8.50 (d, J = 4.2 Hz, 2H), 8.43 (d, J =
.7 Hz, 2H), 8.12 (d, J = 7.5 Hz, 4H), 7.92 – 7.82 (m, 2H), 7.79 (d, J = 7.5 Hz, 2H), 7.65
(t, J = 9.1 Hz, 6H), 7.43 (t, J = 7.4 Hz, 2H), 7.36 (td, J = 7.4, 1.2 Hz, 2H), 5.58 (s, 2H),
5
2
.41 (s, 1H), 4.44 (d, J = 7.1 Hz, 2H), 4.30 (d, J = 7.3 Hz, 1H), 4.20 (d, J = 5.5 Hz, 2H),
1
3
.76 (s, 6H), 2.19 (s, 3H), 1.26 (d, J = 1.3 Hz, 2H), 0.89 (s, 2H). C NMR (126 MHz,
) δ 173.2, 155.7, 149.4, 144.0, 143.8, 141.4, 140.6, 139.7, 137.9, 135.6, 135.0,
34.0, 131.0, 130.4, 130.0, 129.5, 128.9, 128.5, 127.8, 127.6, 127.2, 125.2, 124.7, 120.1,
18.5, 116.0, 105.9, 67.3, 67.1, 49.9, 49.5, 47.2, 32.1, 30.2, 29.8, 29.6, 29.5, 29.1, 22.8,
CDCl
3
1
1
2
1
-1
1.7, 21.4, 18.9, 14.3. IR (ν cm , CHCl
3
) 2972, 2854, 1718, 1605, 1512, 1452, 1407,
376, 1342, 1269, 1213, 1166, 1047, 959, 910, 787, 758, 736. UV/Vis (Chloroform)
-1
3
-1
(λmax/nm, ε mol dm cm ) 447 (71400), 558 (5500), 599 (5416), 638 (5267), 700 (5424).
Fluorescence (in chloroform) λ
f
(Φ ) 714 nm (0.018).
f
Synthesis of compound 6:
To a mixture of oxasmaragdyrin 5 (100 mg, 0.153 mmol) and triethylamine (0.850 ml,
.15 mmol) in dichloromethane solvent, BF .OEt (1.1 ml, 8.0 mmol) was added and
6
3
2
stirred for 30 minutes. The formation of product was checked through TLC. Upon
completion of reaction, the solvent was evaporated and crude solid was subjected to
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European Journal of Organic Chemistry
10.1002/ejoc.201701090
basic-alumina column chromatography using dichloromethane/petroleum ether as solvent
1
to give pure compound as light green solid in 80% yield. H NMR (500 MHz,
Chloroform-d) δ 10.30 (d, J = 4.4 Hz, 2H), 10.21 (dd, J = 4.4, 1.9 Hz, 2H), 9.59 (d, J =
4
7
.4 Hz, 2H), 9.48 (s, 2H), 9.00 (d, J = 3.7 Hz, 2H), 8.63 (d, J = 7.6 Hz, 2H), 8.32 (d, J =
.7 Hz, 4H), 8.00 (d, J = 7.7 Hz, 2H), 7.72 (d, J = 7.6 Hz, 4H), 5.16 (s, 2H), 2.82 (s, 6H),
1
3
-
3.70 (s, 2H). C NMR (126 MHz, CDCl
3
) δ 149.9, 147.3, 144.2, 143.9, 140.8, 139.7,
1
1
38.6, 138.0, 135.1, 134.4, 133.1, 131.9, 131.6, 130.9, 130.7, 128.4, 127.1, 126.8, 125.1,
11
24.5, 123.7, 121.9, 120.7, 120.3, 119.0, 118.7, 107.0, 65.5, 64.7, 29.8, 21.8. B NMR
1
9
-1
(
160 MHz, CDCl
3
) δ -12.39. F NMR (471 MHz, CDCl
3
) δ -149.43. IR (ν cm , CHCl )
3
3
7
5
430, 2925, 2857, 1727, 1574, 1471, 1457, 1413, 1390, 1263, 1114, 1075, 1031, 760,
-1
3
-1
15, 666. UV/Vis (Chloroform) (λmax/nm, ε mol dm cm ) 447 (284700), 475 (127000),
92 (11300), 631 (15500), 649 (18300), 705 (39900). Fluorescence (in chloroform) λ
f
f
(Φ ) 714 nm (0.143). Calculated mass: m/z = 698.2667, measured mass: m/z: 698.2695
[
M+].
Synthesis of compound 2:
To the mixture of BF -(4-(methylhydroxy)phenyl) oxasmaragdyrin 6 ( 30 mg, 0.04
mmol) and N-Fmoc proected amino acid (0.126 mmol) in dry CH Cl ,
2
2
2
diisopropylethylamine ( 33µL, 0.19 mmol) and HOBT (20.5 mg, 0.152 mmol) was
added under nitrogen atmosphere. Followed by addition of EDC.HCl (29 mg, 0.152
mmol) was added at 0 ⁰C. The mixture was stirred for 12 hr. The reaction was monitored
by thin layer chromatography which showed formation of less polar spot. Upon
completion of reaction, the mixture was washed with 10% NaHCO (3 × 50 mL). The
3
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European Journal of Organic Chemistry
10.1002/ejoc.201701090
organic layer was collected, dried over anhydrous Na
2
SO
4
and the solvent was
evaporated to give crude product. The crude product was purified using silica gel column
chromatography by EtOAc/Petroleum ether (15%) as eluent to give amioacid conjugate
as green solid in 25-30% yield.
Compound 2a:
1
Yield = 28%; H NMR (400 MHz, Chloroform-d) δ 10.28 (d, J = 4.5 Hz, 2H), 10.21 (dd,
J = 4.5, 2.0 Hz, 2H), 9.56 (d, J = 4.5 Hz, 2H), 9.48 (s, 2H), 9.00 (dd, J = 4.5, 1.8 Hz,
2
H), 8.60 (d, J = 8.0 Hz, 2H), 8.30 (d, J = 8.0 Hz, 4H), 7.95 (d, J = 7.7 Hz, 2H), 7.78 (d,
J = 7.5 Hz, 2H), 7.69 (t, J = 8.5 Hz, 6H), 7.41 (dd, J = 7.5, 1.2 Hz, 2H), 7.37 (dd, J =
7
.4, 1.3 Hz, 2H), 5.62 (s, 2H), 5.45 (s, 1H), 4.52 (d, J = 7.1 Hz, 2H), 4.33 (t, J = 7.2 Hz,
1
3
1
H), 4.27 (d, J = 5.6 Hz, 2H), 2.80 (s, 6H), -3.79 (s, 2H). C NMR (126 MHz, CDCl ) δ
3
1
71.0, 149.9, 143.8, 143.8, 141.5, 139.7, 138.0, 135.4, 134.4, 131.9, 130.9, 130.7, 128.9,
28.4, 128.0, 127.4, 127.2, 125.2, 125.1, 124.5, 123.7, 121.9, 121.1, 120.6, 120.3, 120.2,
1
1
1
1
20.1, 119.9, 118.8, 107.0, 67.6, 58.5, 47.3, 45.9, 29.8, 29.5, 21.8, 18.2, 8.8, 8.3. B
) δ -12.28. F NMR (471 MHz, CDCl
) δ -149.32. IR (ν cm-1,
1
9
NMR (160 MHz, CDCl
3
3
CHCl ) 2922, 2406, 2315, 1725, 1515, 1454, 1380, 1276, 1181, 1053, 907, 780, 760,
3
-
1
3
-1
7
5
7
32, 616. UV/Vis (Chloroform) (λmax/nm, ε mol dm cm ) 447 (175600), 475 (75600),
92 (5890), 631 (8730), 649 (10350), 705 (23400). Fluorescence (in chloroform) λ
f
(Φ )
f
16 nm (0.156). Calculated mass: m/z = 977.3565, measured mass: m/z = 977.3566 [M+].
Compound 2b
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European Journal of Organic Chemistry
10.1002/ejoc.201701090
1
Yield = 27%; H NMR (500 MHz, Chloroform-d) δ 10.31 (d, J = 4.4 Hz, 2H), 10.23 (dd,
J = 4.4, 2.0 Hz, 2H), 9.58 (d, J = 4.4 Hz, 2H), 9.50 (s, 2H), 9.02 (s, 2H), 8.63 (d, J = 7.7
Hz, 2H), 8.32 (d, J = 7.8 Hz, 4H), 7.97 (d, J = 7.6 Hz, 2H), 7.78 (dd, J = 7.6, 3.8 Hz,
2
1
H), 7.69 (d, J = 7.4 Hz, 2H), 7.39 (d, J = 7.0 Hz, 4H), 5.65 (s, 2H), 5.55 (d, J = 7.9 Hz,
H), 4.79 – 4.62 (m, 1H), 4.51 (dt, J = 17.9, 9.0 Hz, 2H), 4.34 (t, J = 7.0 Hz, 1H), 2.82
13
(
s, 6H), 1.69 (d, J = 7.2 Hz, 3H). C NMR (126 MHz, CDCl
3
) δ 171.0, 149.9, 143.8,
1
43.8, 141.5, 139.7, 138.0, 135.4, 134.4, 131.9, 130.9, 130.7, 128.9, 128.4, 128.0, 127.4,
1
27.2, 125.2, 125.1, 124.5, 123.7, 121.9, 121.1, 120.6, 120.3, 120.2, 120.1, 119.9, 118.8,
07.0, 67.6, 58.5, 47.3, 45.9, 29.8, 29.5, 21.8, 18.2, 8.8, 8.3. 11B NMR (160 MHz,
1
1
9
-1
CDCl
3
) δ -12.29. F NMR (471 MHz, CDCl
3
) δ -149.45. IR (ν cm , CHCl ) 2922, 2857,
3
1
9
690, 1601, 1523, 1513, 1454, 1378, 1344, 1290, 1249, 1183, 1092, 1066, 1017, 997,
-1
3
-1
27, 909, 782, 732. UV/Vis (Chloroform) (λmax/nm, ε mol dm cm ) 447 (175645), 475
(75652), 592 (6000), 631 (9000), 649 (11200), 705 (24400). Fluorescence (in
chloroform) λ (Φ ) 714 nm (0.165). Calculated mass: m/z = 943.3728, measured mass:
f
f
m/z = 943.3725 [M+].
Compound 2c
1
Yield = 30%; H NMR (500 MHz, Chloroform-d) δ 10.29 (d, J = 4.4 Hz, 2H), 10.21 (dd,
J = 4.5, 2.0 Hz, 2H), 9.56 (d, J = 4.4 Hz, 2H), 9.48 (s, 2H), 9.00 (dd, J = 4.4, 1.9 Hz,
2
H), 8.60 (d, J = 7.6 Hz, 2H), 8.30 (d, J = 7.5 Hz, 4H), 7.89 (d, J = 7.5 Hz, 2H), 7.77 (d,
J = 7.5 Hz, 2H), 7.70 (d, J = 7.5 Hz, 4H), 7.64 (t, J = 6.8 Hz, 2H), 7.46 – 7.32 (m, 8H),
7
4
.26 (s, 2H), 5.58 (d, J = 5.1 Hz, 2H), 5.45 (d, J = 8.3 Hz, 1H), 4.96 (d, J = 7.3 Hz, 1H),
.53 (dd, J = 10.7, 7.2 Hz, 1H), 4.45 (dd, J = 10.7, 7.0 Hz, 1H), 4.29 (t, J = 7.0 Hz, 2H),
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European Journal of Organic Chemistry
10.1002/ejoc.201701090
1
3
3
.34 (d, J = 5.9 Hz, 2H), 2.80 (s, 6H), -3.81 (d, J = 10.2 Hz, 2H). C NMR (101 MHz,
CDCl ) δ 171.6, 155.7, 149.8, 143.7, 141.3, 139.5, 137.9, 134.9, 134.2, 131.6, 130.6,
29.5, 128.7, 128.5, 128.3, 127.7, 127.3, 127.1, 125.1, 124.9, 124.2, 123.6, 121.8, 120.6,
3
1
1
1
2
5
1
1
20.2, 120.0, 106.9, 67.3, 67.1, 55.0, 47.2, 38.4, 21.6. B NMR (160 MHz, CDCl
3
) δ -
) 2928, 2854, 2355,
325, 1725, 1515, 1454, 1378, 1349, 1276, 1254, 1185, 1095, 1053, 1022, 780, 758, 739,
1
9
-1
2.32. F NMR (471 MHz, CDCl
3
) δ -149.30. IR (ν cm , CHCl
3
-1
3
-1
80. UV/Vis (Chloroform) (λmax/nm, ε mol dm cm ) 447 (299200), 475 (122400), 592
105200), 631 (14800), 649 (17800), 705 (40400). Fluorescence (in chloroform) λ (Φ
15 nm (0.167). Calculated mass: m/z = 1067.4035, measured mass: m/z = 1067.4037
(
f
f
)
7
[
M+].
Compound 2d:
1
Yield = 25%; H NMR (400 MHz, Chloroform-d) δ 10.29 (d, J = 4.4 Hz, 2H), 10.21 (dd,
J = 4.4, 1.9 Hz, 2H), 9.56 (d, J = 4.5 Hz, 2H), 9.48 (s, 2H), 9.00 (dd, J = 4.4, 1.8 Hz,
2
H), 8.60 (d, J = 7.8 Hz, 2H), 8.30 (d, J = 7.9 Hz, 4H), 7.95 (d, J = 7.6 Hz, 4H), 7.76 (d,
J = 5.7 Hz, 2H), 7.72 – 7.65 (m, 6H), 7.46 – 7.32 (m, 4H), 5.99 (d, J = 8.0 Hz, 1H), 5.62
(s, 2H), 4.79 (d, J = 6.4 Hz, 1H), 4.52 (d, J = 7.0 Hz, 2H), 4.31 (t, J = 6.7 Hz, 1H), 2.80
1
3
(
s, 6H), 2.19 (s, 3H), 1.26 (d, J = 1.3 Hz, 2H), 0.89 (s, 2H), -3.82 (s, 2H). C NMR (126
) δ 172.3, 156.2, 150.0, 144.0, 143.8, 141.5, 139.7, 138.1, 137.6, 135.1,
34.8, 134.4, 132.1, 131.8, 131.0, 130.8, 128.6, 128.4, 127.9, 127.3, 125.2, 125.1, 124.4,
MHz, CDCl
3
1
1
3
1
23.8, 122.0, 120.8, 120.4, 120.2, 118.2, 107.1, 67.9, 67.6, 67.3, 53.6, 53.3, 47.4, 38.9,
2.2, 32.1, 30.1, 29.8, 29.5, 22.8, 21.8, 15.8, 14.7, 14.2. 11B NMR (160 MHz, CDCl
3
) δ -
1
9
-1
2.26. F NMR (376 MHz, CDCl
3
) δ -149.36. IR (ν cm , CHCl ) 2922, 2850, 2322,
3
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European Journal of Organic Chemistry
10.1002/ejoc.201701090
1
7
900, 1810, 1723, 1601, 1512, 1454, 1378, 1344, 1252, 1181, 1095, 1070, 1017, 758,
-1
3
-1
12. UV/Vis (Chloroform) (λmax/nm, ε mol dm cm ) 447 (244200), 475 (100200), 592
(Φ
14 nm (0.159). Calculated mass: m/z = 1051.3755, measured mass: m/z = 1051.3766
(83000), 631 (12000), 649 (14400), 705 (32800). Fluorescence (in chloroform) λ
f
f
)
7
[
M+].
Keywords: Oxasmaragdyrin, Oxasmaragdyrin-Amino Acid Conjugates, Expanded
porphyrins, NIR Fluorophores
References:
[
1] R. B. Woodward Aromaticity: An international symposium Sheffield, 1966; The
Chemical society London, 1966; Special Publication no: 21.
2] (a) T. Chatterjee, A. Srinivasan, M. Ravikanth, T. K. Chandrashekar, Chem. Rev.
017, 117, 3329-337. (b) Y. Pareek, M. Ravikanth, T. K. Chandrashekar, Acc. Chem.
[
2
Res., 2012, 45, 1801–1816. (c) S. J. Narayanan, B. Sridevi, T. K. Chandrashekar, Org.
Lett. 1999, 4, 587-590. (d) B. Sridevi, S. J. Narayanan, R. Rao, T. K. Chandrashekar,
Inorg. Chem. 2000, 39, 3669-3677. (e) R. Misra, R. Kumar, V. Prabhuraja, T. K.
Chandrashekar, J. Photochem. Photobio A. 2005, 175, 108-117.
[
[
3] M. R. Rao, M. Ravikanth, J. Org. Chem. 2011, 76, 3582-3587.
4] (a) A. Jasat, D. Dolphin, Chem. Rev. 1997, 97, 2267-2340. (b) A. Osuka, S. Saito,
Chem. Commun., 2011, 47, 4330-4339. (c) S. Saito, A. Osuka, Angew. Chem. Int. Ed.
011, 50, 4342 – 4373.
2
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201701090
[
5] (a) J. O. Escobedo, O. Rusin, S. Lim, R. M. Strongin, Curr. Opin. Chem. Biol., 2010,
1
3
4, 64-70; (b) M. Ethirajan, Y. Chen, P. Joshi, R. K. Pandey, Chem. Soc. Rev. 2011, 40,
40-362; (c) M. K. Kumova, H. A. Collins, M. Balaz, E. Dahlsetdt, J. A. Levitt, N.
Sergent, K. Suhling, M. Drobizhev, N. S. Markarov, A. Rebane, H. L. Anderson, D.
Phillips, Org. Biomol. Chem. 2009, 7, 889-896.
[
6] (a) N. Kobayashi, T. Furuyama, K. Satoh, J. Am. Chem. Soc. 2011, 133, 19642-
9645; (b) H. Isago, Y. Kagaya, Inorg. Chem. 2012, 51, 8447–-8454; (c) B. J. Brennan,
Y. C. Lam, P. M. Kim, X. Zhang, G. W. Brudvig, ACS Appl. Mater. Interfaces 2015, 7,
6124-16130.
7] (a) G. M. Fischer, M. Isomaki-Krondahl, I. Gottker-Schnetmann, E. Daltrozzo, A.
1
1
[
Zumbusch, Chem. Eur. J. 2009,15,4857-4864. (b) B.Tang, F. Yu, P. Li, L. L. Tong, X.
Duan, T. Xie, X. Wang, J. Am. Chem. Soc. 2009, 131, 3016-3023. (c) W. Pham, L.
Cassell, A. Gillman, D. Koktysh, J. C. Gore, Chem. Commun. 2008, 16, 1895-1897.
[
8] (a) K. Umezawa, D. Citterio, K. Suzuki, Anal. Sci. 2008, 24, 213-217. (b) N. Fu, J. J.
Gassensmith, B. D. Smith, Supramol. Chem. 2009, 21, 118–124. (c) E. Arunkumar, C. C.
Forbes, B. C. Noll, B. D. Smith, J. Am. Chem. Soc. 2005, 127, 3288-3289. (d) J. R.
Johnson, N. Fu, E. Arunkumar, W. M. Leevy, S. T. Gammon, D. Piwnica-Worms, B. D.
Smith, Angew. Chem. Int. Ed. 2007, 46, 5528-5531.
[
9] (a) K. Umezawa, A. Matsui, Y. Nakamura, D. Citterio, K. B. Suzuki, Chem. Eur. J.
009,15, 1096-1106. (b) K. Umezawa, Y. Nakamura, H. Makino, D. Citterio, K. B.
2
Suzuki, J. Am. Chem. Soc. 2008, 130, 1550-1551. (c) A. Loudet, R. Bandichhor, K.
Burgess, A. Palma, S. O. McDonnell, M. J. Hall, D. F. O’Shea, Org. Lett. 2008, 10,
4
771-4774.
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201701090
[
10] (a) S. T. Meek, E. E. Nesterov, T. M. Swager, Org. Lett. 2008, 10, 2991-2993. (b) E.
E. Nesterov, J. Skoch, B.T. Hyman, W. E. Klunk, B. J. Bacskai, T. M. Swager, Angew.
Chem. Int. Ed. 2005, 44, 5452-5456.
[
11] Y. J. Yang, M. Lowry, X. Y. Xu, J. O. Escobedo, M. Sibrian-Vazcluez, L. Wong, C.
M. Schowalter, T. J. Jensen, F. R. Fronczek, I. M. Warner, Proc. Natl. Acad. Sci. U. S. A.
008, 105, 8829-8834.
12] (a) M. K. Kuimova, H. A. Collins, M. Balaz, E. Dahlstedt, J. A. Levitt, N. Sergent,
2
[
K. Suhling, M. Drobizhev, N. S. Makarov, A. Rebane, H. L. Anderson, D. Phillips, Org.
Biomol. Chem. 2009, 7, 889-896. (b) H. L. Kee, R. Nothdurft, C. Muthiah, J. R. Diers, D.
Fan, M. Ptaszek, D. F. Bocian, J. S. Lindsey, J. P. Culver, D. Holten, Photochem.
Photobiol. 2008, 84, 1061-1072. (c) I. V. Nesterova, V. T. Verdree, S. Pakhomov, K. L.
Stricker, M. W. Allen, R. P. Hammer, S. A. Soper, Bioconjugate Chem. 2007, 18, 2159-
2
168. (d) I.V. Nesterova, S. S. Erdem, S. Pakhomov, R. P. Hammer, S. A. Soper, J. Am.
Chem. Soc. 2009, 131, 2432-2433.
13] (a) H. Abrahamse, M. R. Hamblin, Biochem. J. 2016, 473, 347-364. (b) P. A.
[
Waghorn, J. Label Compd. Radiopharm. 2014, 57, 304-309. (c) T. W. B. Liu, J. Chen, G.
Zheng, Amino Acids 2011, 41, 1123–1134. (d) F. Giuntini, C. M. A. Alonsoa, R. W.
Boyle, Photochem. Photobiol. Sci., 2011, 10, 759-791. (e) A. B. Cowley, M. L. Kennedy,
S. Silchenko, G. S. Lukat-Rodgers, K. R. Rodgers, D. R. Benson, Inorg. Chem. 2006, 45,
9
985-10001.
[14] K. Karikis, E. Georgilis, G. Charalambidis, A. Petrou, O. Vakuliuk, T.
Chatziioannou, I. Raptaki, S. Tsovola, I. Papakyriacou, A. Mitraki, D. T. Gryko, A. G.
Coutsolelos, Chem. Eur. J. 2016, 22, 11245-11252.
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201701090
[
15] (a) J. L. Sessler, A. Andrievsky, Chem. Eur. J. 1998, 4, 159-167. (b) V. Kral, J. L.
Sessler, H. Furuta, J. Am. Chem. Soc. 1992,114, 8705-8707.
[
[
[
16] S. Madhu, S. K. Basu, S. Jadhav, M. Ravikanth, Analyst 2013, 138, 299-306.
17] P. Y. Heo, C. H. Lee, Bull. Korean Chem. Soc. 1996, 17, 515-519.
18] M. Goutermann, The Phorphyrins (Ed.), Dolphin D. Academic Press: New York,
1
998, Vol. III, Chapter 1.
Entry for the Table of Contents
FULL PAPER
Oxasmaragdyrin-Amino Acid
Conjugates
Kandala Laxman[a,b] and Mangalampalli
Ravikanth*[a]
Page No. – Page No.
Synthesis of Oxasmaragdyrin-Amino
Acid Conjugates
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