Glycosyl Aldehydes: New Scaffolds for the Synthesis of Neoglycoconjugates via Bioorthogonal Oxime Bond Formation

SYNTHESIS

0

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2018, 50, A–O

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en

J. J. Reina et al.

Paper

Synthesis

Glycosyl Aldehydes: New Scaffolds for the Synthesis of Neoglyco-

conjugates via Bioorthogonal Oxime Bond Formation

José J. Reina

H₂N

O

HO

H

HO

3 to 6 steps

Alicia Rioboo

O

OH

O

Javier Montenegro*

0

0-

0

1

6-

5

0

3

2-

0

9

5

O

up to 73% yield

12 examples

1 step

saccharide

glycosyl aldehyde

Centro Singular de Investigación en Química Biolóxica e

Materiais Moleculares (CIQUS), Universidad de Santiago de

Compostela, Campus Vida, Rúa de Jenaro de la Fuente, s/n,

15782 Santiago de Compostela, La Coruña, Spain

javier.montenegro@usc.es

80–90% yield

12 examples

Oxime neo-glycoconjugate

HO

O

Published as part of the Bürgenstock Special Section 2017

Future Stars in Organic Chemistry

N

O

No side products

Aqueous mild conditions

Glycan stereochemistry control

Received: 19.10.2017

Accepted after revision: 05.12.2017

Published online: 02.01.2018

binding proteins (lectins) is a key challenge for glycobiology

and beyond.^3a

In nature, carbohydrates are conjugated to other bio-

molecules, forming glycopeptides and glycoproteins, glyco-

lipids, glycosylated natural products, and more.^1,2A wide

variety of linkage chemistry connecting carbohydrates and

aglycons (noncarbohydrate part of a conjugate) is observed.

The most prevalent linkage types consist of O-alkyl glyco-

sides (glycolipids and glycoproteins), glycosyl amides (N-

DOI: 10.1055/s-0036-1591082; Art ID: ss-2017-z0681-op

Abstract The straightforward preparation of glycosyl neoconjugates

by oxime (or hydrazone) bond formation represents a key bioorthogo-

nal tool in chemical biology. However, when this strategy is employed

by reacting the reducing end of the glycan moiety, the configuration

and the stereochemical information is lost due to partial (or complete)

opening of the glycan cyclic hemiacetal and the formation of the corre-

sponding opened tautomers. We have completed the synthesis of a li-

brary of glycosyl aldehydes to be used as scaffold for the synthesis of

neoglycoconjugates via oxime bond formation. These glycosyl alde-

hydes constitute a simple and accessible alternative to avoid loss of chi-

ral information when conjugating, by oxime (or hydrazone) bonds, the

aldehyde functionality present at the reducing end of natural carbohy-

drates.

glycoproteins),

and

heterocyclic

glycosylamines

(DNA/RNA). Neoglycoconjugates, on the other hand, are

non-natural glycoconjugates. These artificial glycoconju-

gates can, for example, incorporate a new linkage type or

functionality onto the carbohydrate that enables the study

of carbohydrate–protein interactions.⁴Designed glycocon-

jugates have become essential tools for glycobiology⁵such

as glycoconjugates on arrays and surfaces, multivalent gly-

can scaffolds or in the tagging of glycans for bioimaging

purposes.⁶

Key words neoglycoconjugates, glycosyl aldehydes, oxime bond for-

mation, carbohydrates, bioorthogonal chemistry, chemoselective liga-

tion

Glycans are ubiquitous in nature and are not only an im-

portant source of metabolic energy. They are involved in

numerous signaling and recognition events.¹Interactions

between carbohydrates and cell-surface proteins play im-

portant roles in many biological processes, such as viral and

bacterial infections, cell recognition and adhesion, immune

responses, fertilization, and cancer metastasis.¹For this rea-

son, the role of carbohydrates in the development of drugs,

as vaccines, etc., is clearly growing.²Additionally, carbohy-

drates are becoming very important for the design and de-

velopment of many diagnostic tools and for biosensors for

clinical applications.³In the past decade, appreciation of the

ubiquity of glycans and their ability to encode biochemical

information has increased. Furthermore, the understanding

of how chemical information is encoded in glycan struc-

tures and how this information is read out by carbohydrate

Chemoselective reactions and, in particular, bioorthogo-

nal reactions have been developed for the preparation of

neoglycoconjugates.^7–13Bioorthogonal chemistry includes

any chemical reaction that can occur inside living systems

without interfering with native biochemical processes.⁷A

number of chemical ligation strategies have been developed

that fulfill the requirements of bioorthogonality, including

the 1,3-dipolar cycloaddition between azides and cyclooc-

tynes,⁸between nitrones and cyclooctynes,⁹oxime/hydra-

zone formation from aldehydes and ketones,¹⁰the tetrazine

ligation,¹¹the isocyanide-based click reaction,¹²and most

recently, the quadricyclane ligation.¹³

In this context, hydrazone and the oxime bond forma-

tion have frequently been employed for the efficient chemi-

cal ligation of peptides¹⁴as well as for the conjugation of

peptides with carbohydrates¹⁵and oligonucleotides.¹⁶

A

B

J. J. Reina et al.

Paper

Synthesis

major advantage of these ligation techniques is that they do

not require a coupling reagent or any chemical manipula-

tions but mixing the two components such as the alcoxy-

amine and an aldehyde in the case of oxime formation. In

some of these examples, the aglycon was conjugated to the

carbohydrate by oxime bond formation employing the re-

ducing end of the carbohydrate. However, this strategy im-

plies the ring opening and, consequently, the loss of natural

tridimensional conformation of the carbohydrate.¹⁷In the

case of monosaccharides and small oligosaccharides, in

which the reducing carbohydrate residue is involved in the

interaction with the receptor, the activity of the neoglyco-

conjugates could be lost, and this type of chemoselective li-

gation is not suitable. Herein, we report the preparation of a

glycosyl aldehyde library to synthesize neoglycoconjugates

through oxime bond formation. The process consists of gly-

cosylation with allyl alcohol followed by ozonolysis of the

allyl group to afford the final aldehyde glycan. The reactivi-

ty of these glycosyl aldehydes was confirmed by reaction

with O-benzylhydroxylamine. The corresponding oxime-

bond formation was confirmed to proceed with quantita-

tive conversions and excellent isolated yields in aqueous

mild conditions.

glycosylation strategies to prepare the key intermediate al-

lyl-glycosides.

The Fischer methodology was employed to prepare allyl

α-D-mannospyranoside (8) and the allyl α- and β-pyrano-

side of D-glucose (9 and 10), D-galactose (11 and 12), and L-

fucose (13 and 14). The route started with glycosylation of

the unprotected monosaccharides using acetyl chloride and

allyl alcohol at 60 °C. This initial reaction produced a mix-

ture of α- and β-isomers that was difficult to purify. There-

fore, a transient protection of the free hydroxyl groups with

Ac₂O, pyridine and a catalytic amount of 4-(N,N-dimethyl-

amino)pyridine (DMAP) was performed to facilitate the pu-

rification of the anomers. After purification of both isomers

by silica gel chromatography, the deprotection of the acetyl

group using NaOMe in MeOH gave the allyl glycoside 8–14

in moderate to good isolated yields (27–73%; Scheme 1).

Fischer glycosylation reaction is an equilibrium process that

leads to a mixture of ring size isomers and anomeric iso-

mers, which is a clear limitation of the method when only

one of the isomers is required. However, the application of

this protocol allowed access to reasonable amounts of both

(α and β) allylglycopyranosides in a simple synthetic step.

The Fischer glycosylation of GlcNAc and GalNAc is not

applicable because the oxazoline traps the intermediates

and inhibits the allyl glycosylation reactions. In addition,

the application of the Koenigs–Knorr glycosylation with ac-

tivated glycosyl donors, for this particular targets, could

also lead to the formation of the collateral oxazoline prod-

uct.¹⁸Therefore, given to the propensity of GlcNAc and Gal-

The target carbohydrate library was composed of the

monosaccharides D-mannose (Man), D-glucose (Glc), D-ga-

lactose (Gal), L-fucose (Fuc), N-acetyl-D-galactosamine (Gal-

NAc), and N-acetyl-D-glucosamine (GlcNAc), the disaccha-

rides maltose and lactose and the branched mannose tri-

saccharide Manα1,3[Manα1,6]Man. We employed three

A. General procedure of Fischer's glycosylation strategy

AcO

HO

1. AcCl, allyl alcohol

2. Ac₂O, Pyr, DMAP

O

MeONa

MeOH

O

OH

O

allyl glycoside

free saccharide

protected allyl glycoside

8–14

1–7

Allyl glycosides obtained by Fischer's glycosylation

OH

O

OH

O

HO

OH

O

HO

Me

O

OH

HO

O

OH

α-fucose

α-mannose

8 (73%)

α-glucose

9 (31%)

α-galactose

11 (27%)

13 (40%)

OH

O

OH

O

HO

O

OH

O

Me

O

OH

β-glucose

10 (37%)

β-galactose

12 (40%)

β-fucose

14 (32%)

Scheme 1 Fisher’s glycosidation strategy for the synthesis of allyl-glycosides 8–14

C

J. J. Reina et al.

Paper

Synthesis

NAc glycosyl donors to form this oxazoline, we decided to

synthesize the allyl-glycosides of GlcNAc (21) and GalNAc

(22) via the corresponding oxazoline donor and using TfOH

as reaction promoter, as shown in the Scheme 2.

In the case of lactose and maltose disaccharides, any of

the glycosylation methods previously described could be

applied. However, the application of the Fischer methodolo-

gy in the synthesis of a disaccharide might lead to alcoholy-

sis of the interglycosidic linkage.²⁰Thus, β-lactose and

maltose allyl glycosides 25 and 28 were synthesized by di-

rect glycosylation of peracetylated donor 23 and 26 with al-

lyl alcohol using a large excess of BF₃·OEt₂as promoter,²¹

followed by deprotection of the acetyl group using NaOMe

in MeOH (Scheme 2). The β-stereochemical outcome of the

glycosylation was determined by the presence of the neigh-

boring acetyl group at position C2, which provides anchi-

meric assistance for the formation of a 1,2-trans stereo-

chemical arrangement.

The allyl derivative of the branched mannose trisaccha-

ride Manα1,3[Manα1,6]Man (34) was synthesized from the

allyl α-mannose (8) by following a multistep sequence²²

(Scheme 3). The strategy starts with selective protection of

the primary hydroxyl group on C6 by using the bulky

TBDMS-Cl and imidazole to give 29 with a good isolated

yield after chromatography purification (78%).²³Compound

Starting from the GlcNAc (15) and GalNAc (16), the ox-

azoline was directly formed by following the procedure de-

scribed by Hackam and co-workers,¹⁹using TMSOTf at 60 °C

in 1,2-dichloroethane (DCE) as solvent, the oxazolines 17

and 18 were obtained in quantitative yield. Subsequently,

17 and 18 were glycosylated by using allyl alcohol as accep-

tor and TfOH as promoter in a sealed reaction vessel in CH₂-

Cl₂at 60 °C. After SiO₂chromatography purification, the

peracetylated β-allyl glycosides of GlcNAc 19 and GalNAc

20 were obtained with excellent yields of 89% and 85%, re-

spectively. Finally, deprotection of the acetyl group using

NaOMe in MeOH gave allyl glycosides 21 and 22 in quanti-

tative yields. This stereoselective strategy led only to the β-

isomers of GlcNAc and GalNAc because the attack of the al-

lyl alcohol could only proceed from the β-face of the mono-

saccharides due to the blocking of the α-face by the oxazo-

line ring.

B. General procedure of oxazoline glycosylation strategy

R¹

OAc

O

OAc

O

OAc

R¹

OH

MeONa

MeOH

TMSOTf

R²

AcO

TfOH, allyl alcohol

DCM, 60 °C

R²

AcO

R²

AcO

O

R²

HO

O

OAc

O

1,2-DCE

60 °C

N

NHAc

O

NHAc

R¹= H, R²= OAc

17 (quant.)

R¹= OAc, R²= H

18 (98%)

R¹= H, R²= OAc

19 (82%)

R¹= OAc, R²= H

20 (85%)

R¹= H, R²= OH

21 (quant.)

R¹= OH, R²= H

22 (quant.)

15

R¹= OAc, R²= H

16

OH

O

OH

HO

O

HO

O

HO

NHAc

β-NHAc-glucosamine

β-NHAc-galactosamine

21

22

C. Synthesis of allyl-β-lactoside (25) and allyl-β-maltoside (28)

allyl alcohol

BF₃⋅OEt₂

OAc

O

OAc

O

OH

OAc

O

OAc

O

OH

AcO

HO

MeONa

O

OAc

O

AcO

O

AcO

O

HO

MeOH

DCM

0 °C to r.t.

OAc

OH

OAc

OH

23

24 (62%)

25 (quant.)

OAc

OH

allyl alcohol

BF₃⋅OEt₂

O

AcO

HO

MeONa

MeOH

OAc

O

OH

O

AcO

HO

DCM

0 °C to r.t.

O

OAc

O

AcO

O

AcO

O

HO

OAc

OH

26

27 (65%)

28 (quant.)

Scheme 2 Synthetic strategy for the synthesis of allyl glycosides 21, 22, 25, and 28

D

J. J. Reina et al.

Paper

Synthesis

1. MeC(OMe)₃, CSA

MeCN

TBDMSO

BzO

OAc

O

TBDMSO

HO

OH

O

HO

TBDMSCl

imidazole

OH

O

HO

2. Bz₂O, Et₃N, 4-DMAP

3. 1 M HCl (aq), AcOEt

DMF

O

8

29 (78%)

30 (quant.)

1 M TBAF

THF

AcOH

BzO

OBz

O

HO

OH

O

BzO

OBz

O

BzO

HO

BzO

O

CCl₃

O

OH

HO

BzO

HO

OAc

O

OAc

O

32

O

HO

O

BzO

O

NaOMe, MeOH

NaOH, H₂O

O

HO

O

BzO

TMSOTf, 4 Å MS

CH₂Cl₂

O

BzO

OH

HO

OBz

34 (90%)

33 (quant.)

31 (75%)

Scheme 3 Synthetic strategy for the synthesis of branched mannose trisaccharide Manα1,3[Manα1,6]Man (34)

29 was treated with trimethyl orthoacetate and a catalytic

amount of 10-camphorsulfonic acid (CSA) to form the ace-

tyl orthoester with the hydroxyl groups at positions C2 and

C3. It was not possible to isolate this orthoester because of

partial hydrolysis of the orthoester functionality during the

chromatographic purification. Treatment of the orthoester

intermediate with Bz₂O, Et₃N and a catalytic amount of

DMAP gave the selective benzoylation of the hydroxyl

group at position C4. Finally, addition of 1 M HCl led to par-

tial hydrolysis of the orthoester to obtain compound 30

with the hydroxyl group at position C2 orthogonally pro-

tected with an acetate group and with the hydroxyl group

at C3 unprotected.²⁴After that, selective deprotection of the

silyl protected primary hydroxyl group using tetrabutylam-

monium fluoride (TBAF) in tetrahydrofuran (THF) afforded

mannose 31 in good yield.

The benzoylated trichloroacetimidate glycosyl donor 32

was prepared by following reported procedures.²²The tar-

geted trimannosides 33 incorporates the α-linkage, which

is favored because of the neighboring group at the C2 posi-

tion of the glycosyl donors. Trisaccharide 33 was prepared

by reaction of glycosyl donor 32 with glycosyl acceptors 31

using trimethylsilyltriflate (TMSOTf) as promoter at 0 °C

with quantitative yield. The allyl trisaccharide was pre-

pared by deprotection of acetyl and benzoyl groups under

classical Zemplén conditions (NaOMe/MeOH) to afford the

final compound 34 in quantitative yield.

ferent intermediates could be trapped as oximes after con-

densation with the corresponding alkoxyamine (Scheme 4).

To demonstrate the potential utility of the strategy for bio-

orthogonal conjugation, the glycosyl aldehydes were react-

ed with O-benzylhydroxylamine to form the corresponding

oxime neoglycoconjugates. This reaction was tested for all

the prepared glycosyl aldehydes under physiologically com-

patible conditions such as water at 40 °C for 30 min. The fi-

nal glycosyl acetaldehyde O-benzyl oximes 47–58 were pu-

rified by reverse-phase HPLC and lyophilized to isolate the

final products with excellent yields (80–90%).

The straightforward preparation of glycosyl neoconju-

gates by oxime (or hydrazone) bond formation represents a

key bioorthogonal tool in chemical biology.²⁷However,

when this strategy is employed by reacting the reducing

end of the glycan moiety, the configuration and the stereo-

chemical information of the reducing glycan is lost due to

partial (or complete) opening of the glycan cyclic hemiace-

tal and the formation of the corresponding opened tautom-

ers.¹⁷The objective of this work was to develop and to study

the scope of simple synthetic strategies for the preparation

of glycosyl aldehydes that could be efficiently conjugated

with the corresponding nucleophiles (i.e., alkoxyamines) to

afford the corresponding oximes under physiologically

compatible conditions. The methodology included a Fischer

strategy for 43–53, oxazoline strategy for 54–55, and direct

glycosylation of peracetylated donor for 56–57. We also

demonstrate that a multistep sequence employing glycosyl

donor and acceptors could be employed for the preparation

of tri-mannosyl branched glycan aldehydes. The NMR spec-

troscopic analysis of some of these synthesized aldehydes

showed a mixture of different species such as the targeted

aldehyde, the corresponding hydrate, and products of inter-

or intramolecular addition of the hydroxyls to the aldehyde

function. However, these complex mixtures were readily re-

solved by reaction with the alkoxyamine nucleophiles,

leading to the final oxime products.

Finally, glycosyl aldehydes 35–46 were prepared by con-

version of the allyl group into an aldehyde through ozonoly-

sis, with quantitative yields in all cases.²⁵Analysis by NMR

spectroscopy of these glycosyl aldehydes is not trivial, be-

cause at least three different species, in different ratios,

1

could be identified by H NMR spectroscopy in D₂O solu-

tion. These species could be assigned to the aldehyde, the

hydrate and, in some cases, the cyclic six-membered-ring

hemiacetals formed through ring closure of the aldehyde

with the hydroxyls in position OH-2.²⁶However, these dif-

E

J. J. Reina et al.

Paper

Synthesis

D. General procedure for the synthesis of oxime neoglycoconjugates

H₂N

O

1. O_3,MeOH

–78 °C

HO

O

N

2. Me₂S

H₂O

50 °C

allyl glycoside

glycosyl aldehydes

E/Z mixture of oxime

neoglyconjugates

8–14, 21, 22

25, 28, 34

35–46

47–58

OH

O

HO

OH

O

OH

O

HO

O

HO

N

49 (83%)

O

OH

N

48 (80%)

47 (85%)

OH

O

N

HO

OH

HO

O

Me

O

HO

OH

N

HO

OH

O

N

OH

50 (80%)

51 (90%)

52 (85%)

OH

N

HO

O

OH

O

Me

O

OH

O

HO

O

NHAc

O

N

OH

NHAc

53 (90%)

54 (90%)

55 (83%)

OH

O

OH

HO

OH

O

OH

HO

O

HO

O

HO

O

HO

N

OH

HO

OH

57 (80%)

56 (85%)

O

HO

O

OH

O

HO

O

N

HO

O

OH

58 (85%)

Scheme 4 Synthesis of oxime neoglycoconjugates 47–58

In summary, we have completed the synthesis of a li-

brary of glycosyl aldehydes to be used as scaffold for the

synthesis of neoglycoconjugates via chemoselective ligation

reactions, in particular, as oxime bond formation. These

glycosyl aldehydes constitute a simple and accessible alter-

native to avoid loss of chiral information when conjugating

the aldehyde functionality present at the reducing end of

natural carbohydrates. The synthesized glycosyl aldehydes

were bioorthogonally conjugated with the corresponding

alkoxyamines by incubation in water at 40 °C. This strategy

minimizes the potential loss of the natural tridimensional

conformation of the carbohydrate when directly conjugated

by oxime bonds to the organic scaffolds such as rigid mole-

cules, peptides, and polymers.

Reagents and solvents were purchased as reagent grade and used

without further purification. Silica gel 60 (230–400 mesh, 0.015–0.04

mm) for column chromatography was purchased from Merck. Thin-

layer chromatography (TLC) was performed on aluminum sheets

coated with silica gel 60 F₂₅₄purchased from Merck and visualized by

UV light. NMR spectra were recorded with a Bruker AC 500 with sol-

vent peaks as reference. ¹H and ¹³C NMR spectra were obtained from

solutions in CDCl₃and CD₃OD and D₂O at 298 K. Coupling constants

(J) are reported in Hz. Splitting patterns are described by as: s, singlet;

br. s, broad singlet; d, doublet; t, triplet; q, quartet; dd, doublet of

doublet; ddd, doublet of doublet of doublet; dddd, doublet of doublet

of doublet of doublet; td, triplet of doublet; dt, doublet of triplet; m,

multiplet. ¹H NMR spectra are reported as: chemical shift, multiplici-

ty, coupling constant(s), number(s) of proton. All the assignments

were confirmed by one- and two-dimensional NMR experiments

(COSY and HSQC). HRMS spectra were recorded with electrospray

F

J. J. Reina et al.

Paper

Synthesis

ionization (ESI) with a Bruker Microtof mass spectrometer using

MeOH or CH₃CN/H₂O as solvent system. High-performance liquid

chromatography (HPLC) semipreparative purification was carried out

with a JASCO MD-4015 with an Agilent Eclipse XDB-C18 column [Nu-

cleosil 100–7 C18; Gradient: H₂O (0.1% TFA)/CH₃CN (0.1% TFA),

95:5→5:95 (0→10 min)]. t_Rretention time.

5.2, 1.4 Hz, 1 H, OCH₂CH=CH₂), 4.09–4.00 (m, 3 H, H5 + H6 +

OCH₂CH=CH₂), 2.10 (s, 3 H, OCOCH₃), 2.07 (s, 3 H, OCOCH₃), 2.03 (s,

3 H, OCOCH₃), 2.01 (s, 3 H, OCOCH₃).

¹³C NMR (CDCl₃, 125 MHz): δ = 170.6 (C=O), 171.1 (C=O), 171.1 (C=O),

169.6 (C=O), 133.1 (OCH₂CH=CH₂), 118.2 (OCH₂CH=CH₂), 94.8 (C1),

70.7 (C2), 70.1 (C3), 68.8 (OCH₂CH=CH₂), 68.5 (C4), 67.3 (C5), 61.9

(C6), 20.7 (OCOCH₃), 20.7 (OCOCH₃), 20.7 (OCOCH₃), 20.6 (OCOCH₃).

Protected Allyl Glycosides 1–7; General Procedure A

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₇H₂₄NaO₁₀: 411.1267; found:

A solution of AcCl (530 μL, 7.45 mmol) in allyl alcohol (18 mL) was

stirred at r.t. for 1 h, then the monosaccharide (Man, Glc, Gal or Fuc)

(2.0 g) was added (in one portion) and the mixture was stirred at

60 °C for 3 h. The mixture was cooled to r.t., then the reaction was

quenched by dropwise addition of Et₃N (2 mL) and the solvent was

evaporated under reduce pressure. Ac₂O (15 mL), Pyr (30 mL) and a

catalytic amount of DMAP were subsequently added to the crude ma-

terial and the solution was stirred at r.t. for 2 h. The mixture was di-

luted in EtOAc (100 mL) and washed with HCl 1 M (3 × 100 mL), NaH-

CO₃sat. soln (3 × 100 mL) and brine (100 mL). The organic phase was

dried over anhydrous MgSO₄and the solvent was evaporated. The

crude material was purified by silica gel column chromatography

(Hex/EtOAc) to obtain the α- and β-pyranosyl isomers of monosac-

charides 1–7.

411.1264.

β-Isomer (3)

R_f0.23 (hexane/EtOAc, 3:1).

¹H NMR (CDCl₃, 500 MHz): δ = 5.90–5.81 (m, 1 H, OCH₂CH=CH₂), 5.28

(ddd, J = 17.2, 3.2, 1.6 Hz, 1 H, OCH₂CH=CH₂), 5.24–5.19 (m, 2 H, H3 +

OCH₂CH=CH₂), 5.10 (t, J = 9.7 Hz, 1 H, H4), 5.03 (dd, J = 9.6, 8.0 Hz, 1 H,

H2), 4.57 (d, J = 8.0 Hz, 1 H, H1), 4.35 (ddt, J = 13.2, 4.7, 1.5 Hz, 1 H,

OCH₂CH=CH₂), 4.27 (dd, J = 12.3, 4.7 Hz, 1 H, H6), 4.15 (dd, J = 12.3,

2.4 Hz, 1 H, H6), 4.11 (ddt, J = 13.2, 6.1, 1.2 Hz, 1 H, OCH₂CH=CH₂),

3.70 (ddd, J = 10.0, 4.7, 2.5 Hz, 1 H, H5), 2.10 (s, 3 H, OCOCH₃), 2.06 (s,

3 H, OCOCH₃), 2.03 (s, 3 H, OCOCH₃), 2.01 (s, 3 H, OCOCH₃).

¹³C NMR (CDCl₃, 125 MHz): δ = 170.7 (C=O), 170.3 (C=O), 169.4 (C=O),

169.3 (C=O), 133.3 (OCH₂CH=CH₂), 117.7 (OCH₂CH=CH₂), 99.5 (C1),

72.9 (C3), 71.8 (C5), 71.3 (C2), 70.0 (OCH₂CH=CH₂), 68.4 (C4), 61.9

(C6), 20.7 (OCOCH₃), 20.7 (OCOCH₃), 20.6 (OCOCH₃), 20.6 (OCOCH₃).

Allyl-2,3,4,6-tetra-O-acetyl-α-D-mannopyranose (1)

According to General Procedure A, the residue was purified by flash

chromatography on silica gel (Hex/EtOAc, 2:1) to afford the corre-

sponding α-pyranosyl isomer 1.

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₇H₂₄NaO₁₀: 411.1267; found:

411.1263.

Yield: 3.15 g (73%); colorless solid; R_f0.42 (hexane/EtOAc, 2:1).

Allyl-2,3,4,6-tetra-O-acetyl-α-D-galactopyranose (4) and Allyl-

2,3,4,6-tetra-O-acetyl-β-D-galactopyranose (5)

¹H NMR (CDCl₃, 500 MHz): δ = 5.92 (dddd, J = 17.0, 10.3, 6.3, 5.3 Hz,

1 H, OCH₂CH=CH₂), 5.39 (dd, J = 10.0, 3.4 Hz, 1 H, H3), 5.33 (ddd,

J = 17.2, 3.0, 1.5 Hz, 1 H, OCH₂CH=CH₂), 5.31 (t, J = 10.1, 1.5 Hz, 1 H,

H4), 5.29–5.24 (m, 2 H, H2 + OCH₂CH=CH₂), 4.89 (d, J = 1.7 Hz, 1 H,

H1), 4.30 (dd, J = 12.2, 5.3 Hz, 1 H, H6), 4.21 (ddt, J = 12.8, 5.3, 1.4 Hz,

1 H, OCH₂CH=CH₂), 4.13 (dd, J = 12.2, 2.5 Hz, 1 H, H6), 4.08–4.00 (m,

2 H, H5 + OCH₂CH=CH₂), 2.17 (s, 3 H, OCOCH₃), 2.12 (s, 3 H, OCOCH₃),

2.06 (s, 3 H, OCOCH₃), 2.01 (s, 3 H, OCOCH₃).

According to General Procedure A, the residue was purified by flash

chromatography on silica gel (Hex/EtOAc, 2.5:1) to afford the corre-

sponding α-pyranosyl isomer 4 (1.16 g, 27%) and β-pyranosyl isomer

5 (1.72 g, 40%) as colorless solids.

α-Isomer (4)

¹³C NMR (CDCl₃, 125 MHz): δ = 171.0 (C=O), 170.4 (C=O), 170.2 (C=O),

170.1 (C=O), 133.3 (OCH₂CH=CH₂), 118.8 (OCH₂CH=CH₂), 97.0 (C1),

70.1 (C2), 69.5 (C3), 69.1 (OCH₂CH=CH₂or C5), 69.0 (OCH₂CH=CH₂or

C5), 66.6 (C4), 62.9 (C6), 21.3 (OCOCH₃), 21.1 (OCOCH₃), 21.1 (OCO-

CH₃), 21.0 (OCOCH₃).

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₇H₂₄NaO₁₀: 411.1267; found:

411.1259.

R_f0.34 (hexane/EtOAc, 2.5:1).

¹H NMR (CDCl₃, 500 MHz): δ = 5.93–5.84 (m, 1 H, OCH₂CH=CH₂), 5.47

(dd, J = 3.4, 1.3 Hz, 1 H, H4), 5.39 (ddd, J = 11.9, 3.4, 1.6 Hz, 1 H, H3),

5.32 (ddd, J = 17.3, 3.4, 1.7 Hz, 1 H, OCH₂CH=CH₂), 5.24 (ddd, J = 10.4,

2.8, 1.4 Hz, 1 H, OCH₂CH=CH₂), 5.18–5.14 (m, 2 H, H1 + H2), 4.26 (td,

J = 6.6, 1.4 Hz, H5), 4.20 (ddt, J = 13.1, 5.2, 1.5 Hz, 1 H, OCH₂CH=CH₂),

4.13–4.09 (m, 2 H, 2 H6), 4.03 (ddt, J = 13.1, 6.1, 1.4 Hz, 1 H,

OCH₂CH=CH₂), 2.15 (s, 3 H, OCOCH₃), 2.09 (s, 3 H, OCOCH₃), 2.06 (s,

3 H, OCOCH₃), 2.00 (s, 3 H, OCOCH₃).

¹³C NMR (CDCl₃, 125 MHz): δ = 170.4 (C=O), 170.4 (C=O), 170.3 (C=O),

170.0 (C=O), 133.2 (OCH₂CH=CH₂), 118.0 (OCH₂CH=CH₂), 95.3 (C1),

68.8 (OCH₂CH=CH₂), 68.1 (C4), 68.1 (C2), 67.6 (C3), 66.4 (C5), 61.7

(C6), 20.8 (OCOCH₃), 20.7 (OCOCH₃), 20.7 (OCOCH₃), 20.6 (OCOCH₃).

Allyl-2,3,4,6-tetra-O-acetyl-α-D-glucopyranose (2) and Allyl-

2,3,4,6-tetra-O-acetyl-β-D-glucopyranose (3)

According to General Procedure A, the residue was purified by flash

chromatography on silica gel (Hex/EtOAc, 3:1) to afford the corre-

sponding α-pyranosyl isomer 2 (1.34 g, 31%) and α-pyranosyl isomer

3 (1.60 g, 37%) as colorless solids.

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₇H₂₄NaO₁₀: 411.1267; found:

411.1260.

α-Isomer (2)

R_f0.29 (hexane/EtOAc, 3:1).

β-Isomer (5)

¹H NMR (CDCl₃, 500 MHz): δ = 5.92–5.84 (m, 1 H, OCH₂CH=CH₂), 5.51

(t, J = 9.8 Hz, 1 H, H3), 5.32 (ddd, J = 17.2, 3.2, 1.6 Hz, 1 H,

OCH₂CH=CH₂), 5.23 (ddd, J = 10.4, 3.0, 1.5 Hz, 1 H, OCH₂CH=CH₂), 5.11

(d, J = 3.7 Hz, 1 H, H1), 5.07 (t, J = 9.8 Hz, 1 H, H4), 4.90 (dd, J = 10.2,

3.8 Hz, 1 H, H2), 4.26 (dd, J = 12.3, 4.5 Hz, 1 H, H6), 4.20 (ddt, J = 13.0,

R_f0.25 (hexane/EtOAc, 2.5:1).

¹H NMR (CDCl₃, 500 MHz): δ = 5.83 (dddd, J = 17.3, 10.5, 6.1, 4.9 Hz,

1 H, OCH₂CH=CH₂), 5.37 (dd, J = 3.5, 1.2 Hz, 1 H, H4), 5.30–5.17 (m,

3 H, H2 + OCH₂CH=CH₂), 5.01 (dd, J = 10.4, 3.5 Hz, 1 H, H3), 4.50 (d,

J = 8.0 Hz, 1 H, H1), 4.35 (ddt, J = 13.2, 5.0, 1.6 Hz, 1 H, OCH₂CH=CH₂),

G

J. J. Reina et al.

Paper

Synthesis

4.17 (dd, J = 11.3, 6.5 Hz, 1 H, H6), 4.15–4.06 (m, 2 H, H6

+

Allyl-α-D-mannopyranose (8)

OCH₂CH=CH₂), 3.89 (td, J = 6.7, 1.3 Hz, 1 H, H₅), 2.14 (s, 3 H, OCOCH₃),

2.04 (s, 3 H, OCOCH₃), 2.03 (s, 3 H, OCOCH₃), 1.97 (s, 3 H, OCOCH₃).

According to General Procedure B, compound 8 was obtained (404

mg, quant.) as a colorless solid without further purification.

¹³C NMR (CDCl₃, 125 MHz): δ = 170.8 (C=O), 170.6 (C=O), 170.5 (C=O),

169.8 (C=O), 133.7 (OCH₂CH=CH₂), 117.9 (OCH₂CH=CH₂), 100.5 (C1),

71.3 (C3), 71.0 (C5), 70.4 (OCH₂CH=CH₂), 69.2 (C2), 67.4 (C4), 61.7

(C6), 21.1 (OCOCH₃), 21.0 (OCOCH₃), 21.0 (OCOCH₃), 20.9 (OCOCH₃).

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₇H₂₄NaO₁₀: 411.1267; found:

411.1262.

¹H NMR (CD₃OD, 500 MHz): δ = 5.96 (dddd, J = 17.3, 10.7, 6.0, 5.1 Hz,

1 H, OCH₂CH=CH₂), 5.32 (dq, J = 17.3, 1.8 Hz, 1 H, OCH₂CH=CH₂), 5.19

(dq, J = 10.4, 1.5 Hz, 1 H, OCH₂CH=CH₂), 4.81 (d, J = 1.7 Hz, 1 H, H1),

4.24 (ddt, J = 13.1, 5.1, 1.6 Hz, 1 H, OCH₂CH=CH₂), 4.03 (ddt, J = 13.1,

6.0, 1.4 Hz, 1 H, OCH₂CH=CH₂), 3.85 (dd, J = 11.8, 2.4 Hz, 1 H, H6), 3.83

(dd, J = 3.4, 1.7 Hz, 1 H, H2), 3.76–3.70 (m, 2 H, H3 + H6), 3.63 (t,

J = 9.5 Hz, 1 H, H4), 3.55 (ddd, J = 9.8, 5.8, 2.3 Hz, 1 H, H5).

Allyl-2,3,4-tri-O-acetyl-α-L-fucopyranose (6) and Allyl-2,3,4-tri-O-

acetyl-β-L-fucopyranose (7)

¹³C NMR (CD₃OD, 125 MHz):

δ = 135.9 (OCH₂CH=CH₂), 117.6

(OCH₂CH=CH₂), 101.1 (C1), 75.1 (C5), 73.1 (C3), 72.6 (C2), 69.2

(OCH₂CH=CH₂), 69.1 (C4), 63.4 (C6).

HRMS (ESI): m/z [M + Na]⁺calcd for C₉H₁₆NaO₆: 243.0845; found:

243.0837.

According to General Procedure A, the residue was purified by flash

chromatography on silica gel (Hex/EtOAc, 4:1) to afford the corre-

sponding α-pyranosyl isomer 6 (1.29 g, 40%) and β-pyranosyl isomer

7 (1.03 g, 32%) as colorless solids.

Allyl-α-D-glucopyranose (9)

α-Isomer (6)

According to General Procedure B, compound 9 was obtained (315

R_f0.55 (hexane/EtOAc, 1:1).

mg, quant.) as a colorless solid without further purification.

¹H NMR (CDCl₃, 500 MHz): δ = 5.94–5.84 (m, 1 H, OCH₂CH=CH₂), 5.41

(dd, 1 H, J = 10.9, 3.3 Hz, H3), 5.35–5.29 (m, 2 H, H4 + OCH₂CH=CH₂),

5.23 (dd, J = 10.4, 1.5 Hz, 1 H, OCH₂CH=CH₂), 5.16 (dd, J = 10.8, 3.7 Hz,

1 H, H2), 5.11 (d, J = 3.6 Hz, 1 H, H1), 4.23–4.16 (m, 2 H, H5 +

OCH₂CH=CH₂), 4.03 (dd, J = 13.3, 6.2 Hz, 1 H, OCH₂CH=CH₂), 2.18 (s,

3 H, OCOCH₃), 2.09 (s, 3 H, OCOCH₃), 2.00 (s, 3 H, OCOCH₃), 1.16 (d,

J = 6.7 Hz, 3 H, H6).

¹H NMR (CD₃OD, 500 MHz): δ = 6.10–5.91 (m, 1 H, OCH₂CH=CH₂),

5.36 (ddd, J = 17.3, 3.4, 1.7 Hz, 1 H, OCH₂CH=CH₂), 5.19 (ddd, J = 10.5,

3.0, 1.5 Hz, 1 H, OCH₂CH=CH₂), 4.85 (d, J = 3.7 Hz, 1 H, H1), 4.25 (ddt,

J = 13.0, 5.2, 1.6 Hz, 1 H, OCH₂CH=CH₂), 4.06 (ddt, J = 13.0, 6.0, 1.4 Hz,

1 H, OCH₂CH=CH₂), 3.83 (dd, J = 11.8, 2.4 Hz, 1 H, H6), 3.72–3.66 (m,

2 H, H3 + H6), 3.60 (ddd, J = 10.0, 5.6, 2.4 Hz, 1 H, H5), 3.42 (dd, J = 9.7,

3.8 Hz, 1 H, H2), 3.37–3.27 (m, 1 H, H4).

¹³C NMR (CDCl₃, 125 MHz): δ = 171.0 (C=O), 170.8 (C=O), 170.4 (C=O),

133.9 (OCH₂CH=CH₂), 118.0 (OCH₂CH=CH₂), 95.7 (C1), 71.6 (C4), 69.0

(OCH₂CH=CH₂), 68.6 (C2 or C3), 68.5 (C2 or C3), 64.9 (C5), 21.2 (OCO-

CH₃), 21.1 (OCOCH₃), 21.0 (OCOCH₃), 16.2 (C6).

¹³C NMR (CD₃OD, 125 MHz):

(OCH₂CH=CH₂), 99.6 (C1), 75.5 (C3), 74.2 (C2), 74.0 (C5), 72.5 (C4),

69.7 (OCH₂CH=CH₂), 69.1 (C4), 63.1 (C6).

HRMS (ESI): m/z [M + Na]⁺calcd for C₉H₁₆NaO₆: 243.0845; found:

243.0837.

δ = 136.0 (OCH₂CH=CH₂), 117.9

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₅H₂₂NaO₈: 353.1212; found:

353.1205.

Allyl-β-D-glucopyranose (10)

β-Isomer (7)

According to General Procedure B, compound 10 was obtained (315

R_f0.45 (hexane/EtOAc, 1:1).

mg, quant.) as a colorless solid without further purification.

¹H NMR (CDCl₃, 500 MHz): δ = 5.83–5.74 (m, 1 H, OCH₂CH=CH₂), 5.20

(d, J = 17.2 Hz, 1 H, OCH₂CH=CH₂), 5.17–5.10 (m, 3 H, H2 + H4 +

OCH₂CH=CH₂), 4.95 (dd, J = 10.5, 3.2 Hz, 1 H, H3), 4.42 (d, J = 7.9 Hz,

1 H, H1), 4.29 (dd, J = 13.4, 4.7 Hz, 1 H, OCH₂CH=CH₂), 4.02 (dd,

J = 13.3, 6.0 Hz, 1 H, OCH₂CH=CH₂), 3.72 (q, J = 6.4, 1 H, H5), 2.10 (s,

3 H, OCOCH₃), 1.98 (s, 3 H, OCOCH₃), 1.91 (s, 3 H, OCOCH₃).

¹H NMR (CD₃OD, 500 MHz): δ = 5.99 (dddd, J = 17.2, 10.5, 6.1, 5.2 Hz,

1 H, OCH₂CH=CH₂), 5.35 (dq, J = 17.3, 1.7 Hz, 1 H, OCH₂CH=CH₂), 5.18

(dq, J = 10.5, 1.5 Hz, 1 H, OCH₂CH=CH₂), 4.40 (ddt, J = 13.1, 5.1, 1.6 Hz,

1 H, OCH₂CH=CH₂), 4.32 (d, J = 7.8 Hz, 1 H, H1), 4.17 (ddt, J = 13.1, 6.0,

1.4 Hz, 1 H, OCH₂CH=CH₂), 3.85 (dd, J = 11.9, 2.1 Hz, 1 H, H6), 3.39–

3.25 (m, 5 H, H3 + H4 + H5), 3.22 (dd, J = 9.8, 7.8 Hz, 1 H, H2).

¹³C NMR (CDCl₃, 125 MHz): δ = 171.1 (C=O), 170.6 (C=O), 169.9 (C=O),

134.0 (OCH₂CH=CH₂), 117.7 (OCH₂CH=CH₂), 100.3 (C1), 71.8 (C3), 70.7

(C2 or C4), 70.3 (C2 or C4), 69.6 (OCH₂CH=CH₂), 69.4 (C5), 21.2 (OCO-

CH₃), 21.1 (OCOCH₃), 21.0 (OCOCH₃), 16.5 (C6).

¹³C NMR (CD₃OD, 125 MHz):

(OCH₂CH=CH₂), 103.8 (C1), 78.5 (C3), 78.4 (C5), 75.5 (C2), 72.1 (C4),

71.5 (OCH₂CH=CH₂), 63.4 (C6).

HRMS (ESI): m/z [M + Na]⁺calcd for C₉H₁₆NaO₆: 243.0845; found:

243.0837.

δ = 136.2 (OCH₂CH=CH₂), 117.8

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₅H₂₂NaO₈: 353.1212; found:

353.1209.

Allyl-α-D-galactopyranose (11)

Deprotected Allyl Glycosides 8–14; General Procedure B

According to General Procedure B, compound 11 was obtained (250

To a solution of protected glycosides (0.07 mmol) in anhydrous MeOH

(1.5 mL), NaOMe (0.01 mmol) was added in one portion and the solu-

tion was stirred at r.t. After TLC showed a complete conversion (ca.

1 h) Amberlite IRA 120H⁺was added until pH 7 and the beads were

filtered off. The solvent was evaporated under vacuum to obtain the

α- and β-deprotected pyranosyl isomers of monosacharides 8–14.

mg, quant.) as a colorless solid without further purification.

¹H NMR (CD₃OD, 500 MHz): δ = 5.97 (dddd, J = 17.3, 10.4, 6.1, 5.2 Hz,

1 H, OCH₂CH=CH₂), 5.33 (ddd, J = 17.3, 3.4, 1.7 Hz, 1 H, OCH₂CH=CH₂),

5.16 (ddd, J = 10.4, 3.0, 1.5 Hz, 1 H, OCH₂CH=CH₂), 4.86 (d, J = 3.3 Hz,

1 H, H1), 4.22 (ddt, J = 13.0, 5.2, 1.5 Hz, 1 H, OCH₂CH=CH₂), 4.03 (ddt,

J = 13.0, 6.1, 1.4 Hz, 1 H, OCH₂CH=CH₂), 3.88 (dd, J = 2.7, 1.3 Hz, 1 H,

H4), 3.81 (td, J = 6.0, 1.2 Hz, 1 H, H5), 3.76 (t, J = 2.6 Hz, 2 H, H2+H3),

3.70 (dd, J = 6.1, 2.0 Hz, 2 H, 2 H6).

H

J. J. Reina et al.

Paper

Synthesis

¹³C NMR (CD₃OD, 125 MHz):

δ

=

136.1 (OCH₂CH=CH₂), 117.9

Allyl-glycosides via Oxazoline Donors

(OCH₂CH=CH₂), 99.9 (C1), 72.9 (C2), 71.9 and 71.5 (C4 and C5), 70.7

(C3), 69.8 (OCH₂CH=CH₂), 63.1 (C6).

HRMS (ESI): m/z [M + Na]⁺calcd for C₉H₁₆NaO₆: 243.0845; found:

2-Methyl-3,4,6-tri-O-acetyl-1,2-deoxy-α-D-glucopyrano[2,1,d]-2-

oxazoline (17)

243.0838.

TMSOTf (1.0 mL, 5.40 mmol) was added at r.t. to a solution of per-

acetylated sugar 15 (2 g, 5.15 mmol) in anhydrous 1,2-dichloroethane

(15 mL). The mixture was stirred for 4 h at 60 °C and allowed to cool

to r.t. To this solution, triethylamine (2.9 mL) was added dropwise

and, after 15 min at r.t., the reaction mixture was diluted with CH₂Cl₂

(50 mL) and washed with a NaHCO₃sat. aq. soln (2 × 50 mL). The or-

ganic layer was dried over anhydrous MgSO₄, filtered, and concentrat-

ed under vacuum. The residue was purified by column chromatogra-

phy on silica gel (CH₂Cl₂/MeOH, 50:1 → 30:1) to afford 17 (1.69 g,

quant.) as a yellow oil.

Allyl-β-D-galactopyranose (12)

According to General Procedure B, compound 12 was obtained

(250 mg, quant.) as a colorless solid without further purification.

¹H NMR (CD₃OD, 500 MHz): δ = 6.01 (dddd, J = 17.3, 10.4, 6.1, 5.2 Hz,

1 H, OCH₂CH=CH₂), 5.37 (ddd, J = 17.3, 3.4, 1.7 Hz, 1 H, OCH₂CH=CH₂),

5.19 (ddd, J = 10.5, 3.0, 1.5 Hz, 1 H, OCH₂CH=CH₂), 4.41 (ddt, J = 12.9,

5.3, 1.6 Hz, 1 H, OCH₂CH=CH₂), 4.30 (d, J = 7.7 Hz, 1 H, H1), 4.19 (ddt,

J = 12.9, 6.1, 1.4 Hz, 1 H, OCH₂CH=CH₂), 3.87 (dd, J = 3.4, 1.1 Hz, 1 H,

H4), 3.80 (dd, J = 11.4, 6.8 Hz, 1 H, H6), 3.76 (dd, J = 11.4, 5.5 Hz, 1 H,

H6), 3.58 (dd, J = 9.7, 7.6 Hz, 1 H, H2), 3.53 (ddd, J = 6.7, 5.4, 1.2 Hz,

1 H, H5), 3.50 (dd, J = 9.7, 3.4 Hz, 1 H, H3).

Spectroscopic and physical data matched those reported.¹⁹

2-Methyl-3,4,6-tri-O-acetyl-1,2-deoxy-α-D-galactopyrano[2,1,d]-

2-oxazoline (18)

¹³C NMR (CD₃OD, 125 MHz):

δ = 136.1 (OCH₂CH=CH₂), 117.7

TMSOTf (1.0 mL, 5.40 mmol) was added at r.t. to a solution of per-

acetylated sugar 16 (2 g, 5.15 mmol) in anhydrous 1,2-dichloroethane

(15 mL). The mixture was stirred for 4 h at 60 °C and allowed to cool

to r.t. To this solution, triethylamine (2.9 mL) was added dropwise

and, after 15 min at r.t., the reaction mixture was diluted with CH₂Cl₂

(50 mL) and washed with a NaHCO₃sat. aq. soln (2 × 50 mL). The or-

ganic layer was dried over anhydrous MgSO₄, filtered and concentrat-

ed under vacuum. The residue was purified by column chromatogra-

phy on silica gel (CH₂Cl₂/MeOH, 50:1 → 30:1) to afford 18 (1.60 g,

98%) as a yellow oil.

(OCH₂CH=CH₂), 104.3 (C1), 76.0 (C5), 75.3 (C3), 72.8 (C2), 71.3

(OCH₂CH=CH₂), 70.6 (C4), 62.8 (C6).

HRMS (ESI): m/z [M + Na]⁺calcd for C₉H₁₆NaO₆: 243.0845; found:

243.0837.

Allyl-α-L-fucopyranoside (13)

According to General Procedure B, compound 13 was obtained

(280 mg, quant.) as a colorless solid without further purification.

¹H NMR (CD₃OD, 500 MHz): δ = 6.00 (dddd, J = 17.3, 10.3, 6.0, 5.3 Hz,

1 H, OCH₂CH=CH₂), 5.36 (ddd, J = 17.3, 3.4, 1.7 Hz, 1 H, OCH₂CH=CH₂),

5.21 (ddd, J = 10.4, 2.8, 1.4 Hz, 1 H, OCH₂CH=CH₂), 4.84 (d, J = 3.0 Hz,

1 H, H1), 4.20 (ddt, J = 13.1, 5.3, 1.5 Hz, 1 H, OCH₂CH=CH₂), 4.07 (ddt,

J = 13.1, 6.1, 1.4 Hz, 1 H, OCH₂CH=CH₂), 4.00 (q, J = 6.7 Hz, 1 H, H5),

3.82–3.76 (m, 2 H, H2 + H3), 3.70 (dd, J = 2.9, 1.3 Hz, 1 H, H4), 1.25 (d,

J = 6.6 Hz, 3 H, 3 H6).

Spectroscopic and physical data matched those reported.¹⁹

Allyl-2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranose

(19)

Freshly distilled allyl alcohol (1.3 mL, 18.83 mmol) was added drop-

wise to a mixture of oxazoline 17 (620 mg, 1.88 mmol) and powdered

4Å molecular sieves in anhydrous CH₂Cl₂(10 mL). The reaction vessel

was sealed, heated at 70 °C, and trifluoromethanesulfonic acid (66 μL,

0.75 mmol) was then added and the reaction mixture was heated at

70 °C for 4 h. The mixture was then allowed to cool to r.t., filtered

through Celite and washed with CH₂Cl₂(2 × 20 mL). The organic layer

was washed with NaHCO₃sat. aq. soln (2 × 50 mL) and brine (50 mL).

The organic phase was dried over anhydrous MgSO₄, filtered and con-

centrated under vacuum to remove the excess of allyl alcohol. The

residue was purified by column chromatography on silica gel

(CH₂Cl₂/MeOH, 100:0 → 100:1), to afford 19 (600 mg, 82%) as a color-

less solid.

¹³C NMR (CD₃OD, 125 MHz):

δ = 136.2 (OCH₂CH=CH₂), 117.8

(OCH₂CH=CH₂), 100.0 (C1), 74.1 (C4), 72.1 (C2 or C3), 70.4 (C2 or C3),

69.9 (OCH₂CH=CH₂), 68.0 (C5), 17.0 (C6).

HRMS (ESI): m/z [M + Na]⁺calcd for C₉H₁₆NaO₅: 227.0895; found:

243.0890.

Allyl-β-L-fucopyranose (14)

According to General Procedure B, compound 14 was obtained (200

mg, quant.) as a colorless solid without further purification.

¹H NMR (CD₃OD, 500 MHz): δ = 6.00 (dddd, J = 17.1, 10.3, 6.0, 5.3 Hz,

1 H, OCH₂CH=CH₂), 5.36 (ddd, J = 17.3, 2.6, 1.3 Hz, 1 H, OCH₂CH=CH₂),

5.19 (ddd, J = 10.5, 2.8, 1.4 Hz, 1 H, OCH₂CH=CH₂), 4.36 (ddt, J = 12.9,

5.3, 1.6 Hz, 1 H, OCH₂CH=CH₂), 4.27 (d, J = 7.3 Hz, 1 H, H1), 4.15 (ddt,

J = 12.9, 6.1, 1.4 Hz, 1 H, OCH₂CH=CH₂), 3.68–3.61 (m, 2 H, H4 + H5),

3.53 (dd, J = 9.7, 7.2 Hz, 1 H, H2), 3.49 (dd, J = 9.7, 3.2 Hz, 1 H, H3),

1.17 (d, J = 7.3 Hz, 3 H, 3 H6).

R_f0.58 (CH₂Cl₂/MeOH, 95:5).

¹H NMR (CDCl₃, 500 MHz): δ = 5.86 (dddd, J = 16.9, 10.4, 6.3, 5.0 Hz,

1 H, OCH₂CH=CH₂), 5.54 (d, J = 8.8 Hz, 1 H, NHAc), 5.34–5.23 (m, 2 H,

H3 + OCH₂CH=CH₂), 5.19 (ddd, J = 10.4, 2.8, 1.4 Hz, 1 H, OCH₂CH=CH₂),

5.06 (t, J = 9.6 Hz, 1 H, H4), 4.71 (d, J = 8.3 Hz, 1 H, H1), 4.33 (ddt,

J = 12.9, 5.0, 1.5 Hz, 1 H, OCH₂CH=CH₂), 4.25 (dd, J = 12.2, 4.8 Hz, 1 H,

H6), 4.13 (dd, J = 12.3, 2.5 Hz, 1 H, H6), 4.08 (ddt, J = 13.0, 6.4, 1.4 Hz,

1 H, OCH₂CH=CH₂), 3.87 (dt, J = 10.6, 8.5 Hz, 1 H, H2), 3.70 (ddd,

J = 10.0, 4.9, 2.5 Hz, 1 H, H5), 2.08 (s, 3 H, OCOCH₃), 2.02 (OCOCH₃),

2.01 (OCOCH₃), 1.94 (NHCOCH₃).

¹³C NMR (CDCl₃, 125 MHz): δ = 171.3 (C=O), 171.1 (C=O), 170.6 (C=O),

169.8 (C=O), 133.9 (OCH₂CH=CH₂), 118.2 (OCH₂CH=CH₂), 100.1 (C1),

72.8 (C3), 72.2 (C5), 70.3 (OCH₂CH=CH₂), 69.1 (C4), 62.6 (C6), 55.2

(C2), 23.7 (NHCOCH₃), 21.1 (OCOCH₃), 21.1 (OCOCH₃), 21.0 (OCOCH₃).

¹³C NMR (CD₃OD, 125 MHz):

δ = 136.3 (OCH₂CH=CH₂), 117.7

(OCH₂CH=CH₂), 104.3 (C1), 75.6 (C3), 73.4 (C4 or C5), 72.7 (C4 or C5),

72.3 (C2), 71.4 (OCH₂CH=CH₂), 17.1 (C6).

HRMS (ESI): m/z [M + Na]⁺calcd for C₉H₁₆NaO₅: 227.0895; found:

243.0891.

I

J. J. Reina et al.

Paper

Synthesis

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₇H₂₅NNaO₉: 410.1427; found:

410.1421.

achieved, Amberlite IRA 120 H⁺was added until pH 7 and the beads

were filtered off. The solvent was evaporated under vacuum to obtain

22 (336 mg, quant.) as a colorless solid.

¹H NMR (CD₃OD, 500 MHz): δ = 5.91 (dddd, J = 17.3, 10.6, 5.8, 4.9 Hz,

1 H, OCH₂CH=CH₂), 5.31 (ddd, J = 17.2, 3.6, 1.8 Hz, 1 H, OCH₂CH=CH₂),

5.17 (ddd, J = 10.7, 3.2, 1.6 Hz, 1 H, OCH₂CH=CH₂), 4.59 (s, 1 H, NHAc),

4.46 (d, J = 8.5 Hz, 1 H, H1), 4.38 (ddt, J = 13.2, 5.0, 1.7 Hz, 1 H,

OCH₂CH=CH₂), 4.12 (ddt, J = 13.3, 5.8, 1.5 Hz, 1 H, OCH₂CH=CH₂), 3.98

(dd, J = 10.7, 8.4 Hz, 1 H, H2), 3.87 (dd, J = 3.4, 1.2 Hz, 1 H, H4), 3.82

(dd, J = 11.4, 6.8 Hz, 1 H, H6), 3.78 (dd, J = 11.4, 5.4 Hz, 1 H, H6), 3.64

(dd, J = 10.7, 3.3 Hz, 1 H, H3), 3.53 (ddd, J = 6.8, 5.4, 1.1 Hz, 1 H, H5),

2.02 (s, 3 H, NHAc).

¹³C NMR (CD₃OD, 125 MHz): δ = 174.5 (C=O), 136.1 (OCH₂CH=CH₂),

117.3 (OCH₂CH=CH₂), 102.6 (C1), 77.2 (C5), 73.7 (C3), 70.1 (C4), 71.1

(OCH₂CH=CH₂), 70.1 (C4), 62.9 (C6), 54.7 (C2), 23.4 (NHCOCH₃).

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₁H₁₉NaO₆: 284.1110; found:

284.1106.

Allyl-2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-galactopyra-

nose (20)

Freshly distilled allyl alcohol (1.35 mL, 19.75 mmol) was added drop-

wise to a mixture of oxazoline 19 (650 mg, 1.97 mmol) and powdered

4Å molecular sieves in anhydrous CH₂Cl₂(10 mL). The reaction vessel

was sealed, heated at 70 °C and trifluoromethanesulfonic acid (70 μL,

0.79 mmol) was then added and the reaction mixture was heated at

70 °C for 4 h. The mixture was then allowed to cool to r.t., filtered

through Celite and washed with CH₂Cl₂(2 × 20 mL). The organic layer

was washed with NaHCO₃sat. aq. soln (2 × 50 mL) and brine (50 mL).

The organic phase was dried over anhydrous MgSO₄, filtered and con-

centrated under vacuum to remove the excess of allyl alcohol. The

residue was purified by column chromatography on silica gel (CH₂-

Cl₂/MeOH, 100:0 → 100:1), to afford 20 (645 mg, 85%) as a colorless

solid.

R_f0.61 (CH₂Cl₂/MeOH, 100:5).

Allyl Disaccharides

¹H NMR (CDCl₃, 500 MHz): δ = 5.87 (dddd, J = 17.0, 10.4, 6.3, 5.1 Hz,

1 H, OCH₂CH=CH₂), 5.46 (d, J = 8.6 Hz, 1 H, NHAc), 5.36 (dd, J = 3.4,

1.4 Hz, 1 H, H4), 5.33–5.25 (m, 2 H, H3 + OCH₂CH=CH₂), 5.22 (ddd,

J=10.4, 3.0, 1.5 Hz, 1 H, OCH₂CH=CH₂), 4.74 (d, J = 8.4 Hz, 1 H, H1),

4.35 (ddt, J = 13.0, 5.1, 1.5 Hz, 1 H, OCH₂CH=CH₂), 4.20–4.06 (m, 3 H,

2 H6 + OCH₂CH=CH₂), 3.97 (dt, J = 11.2, 8.5 Hz, 1 H, H2), 3.91 (td,

J = 6.1, 1.2 Hz, 1 H, H5), 2.14 (s, 3 H, OCOCH₃), 2.04 (OCOCH₃), 2.00

(OCOCH₃), 1.95 (NHCOCH₃).

¹³C NMR (CDCl₃, 125 MHz): δ = 170.8 (C=O), 170.8 (C=O), 170.7 (C=O),

170.6 (C=O), 134.0 (OCH₂CH=CH₂), 118.2 (OCH₂CH=CH₂), 100.3 (C1),

71.1 (C5), 70.4 (OCH₂CH=CH₂), 70.3 (C3), 67.2 (C4), 61.9 (C6), 52.1

(C2), 23.9 (NHCOCH₃), 21.1 (OCOCH₃), 21.1 (OCOCH₃), 21.1 (OCOCH₃).

Allyl Per(acetylated) Lactose (24)

BF₃·Et₂O (0.9 mL, 7.35 mmol) was added dropwise to a cooled solu-

tion (0 °C) of peracetyl-lactose 23 (1.0 g, 1.48 mmol) and allyl alcohol

(150 μL, 2.21 mmol) in anhydrous CH₂Cl₂(10 mL). The reaction mix-

ture was stirred at r.t. for 16 h. The reaction was diluted with CH₂Cl₂

(50 mL) and washed with water (3 × 50 mL), NaHCO₃sat. soln (3 × 50

mL) and brine solution (50 mL). The organic layer was dried over an-

hydrous magnesium sulfate and evaporated to dryness. Finally, the

residue was purified by column chromatography on silica gel (hex-

ane/EtOAc 1:1) to give 24 (620 mg, 62%) as a colorless solid.

R_f0.26 (hexane/EtOAc, 1:1).

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₇H₂₅NNaO₉: 410.1427; found:

410.1419.

¹H NMR (CDCl₃, 500 MHz): δ = 5.81 (dddd, J = 16.9, 10.8, 6.1, 4.9 Hz,

1 H, OCH₂CH=CH₂), 5.32 (dd, J = 3.4, 1.2 Hz, 1 H, H_4B), 5.23 (ddd,

J = 17.2, 3.4, 1.7 Hz, 1 H, OCH₂CH=CH₂), 5.17 (t, J = 1.5 Hz, 1 H, H3A),

5.17 (ddd, J = 10.5, 3.0, 1.5 Hz, 1 H, OCH₂CH=CH₂), 5.08 (dd, J = 10.4,

7.9 Hz, 1 H, H2B), 4.96–4.86 (m, 2 H, H2A + H3B), 4.50 (d, J = 7.9 Hz,

1 H, H1A), 4.46 (d, J = 8.0 Hz, 1 H, H1B), 4.46–4.42 (m, 1 H, H6B), 4.27

(ddt, J = 13.2, 5.0, 1.6 Hz, 1 H, OCH₂CH=CH₂), 4.14–4.01 (m, 5 H,

OCH₂CH=CH₂+ H5B + 2 H6A + H6B), 3.85 (ddd, J = 7.5, 6.3, 1.3 Hz, 1 H,

OCH₂CH=CH₂), 3.78 (t, J = 9.4 Hz, 1 H, H4A), 3.57 (ddd, J = 9.9, 5.1,

2.1 Hz, 1 H, H5A), 2.12 (s, 3 H, OCOCH₃), 2.10 (s, 3 H, OCOCH₃), 2.03

(OCOCH₃), 2.02 (s, 6 H, OCOCH₃), 2.01 (s, 6 H, 2 × OCOCH₃), 1.94 (s,

3 H, OCOCH₃).

¹³C NMR (CDCl₃, 125 MHz): δ = 170.7 (C=O), 170.7 (C=O), 170.5 (C=O),

170.4 (C=O), 170.2 (C=O), 170.0 (C=O), 169.4 (C=O), 133.7

(OCH₂CH=CH₂), 118.0 (OCH₂CH=CH₂), 101.5 (C1B), 99.7 (C1A), 76.7

(C4A), 73.3 (C3A), 73.0 (C5A), 72.1 (C2A), 71.4 (C3B), 71.1 (C5B), 70.4

(OCH₂CH=CH₂), 69.5 (C2B), 67.0 (C4B), 62.4 (C6A), 61.2 (C6A), 21.2

(OCOCH₃), 21.2 (OCOCH₃), 21.01 (OCOCH₃), 21.0 (OCOCH₃), 20.9

(OCOCH₃).

Allyl-2-acetamido-2-deoxy-β-D-glucopyranose (21)

NaOMe (7 mg, 0.13 mmol) was added in one portion to a solution of

19 (300 mg, 0.78 mmol) in anhydrous MeOH (15 mL). The mixture

was stirred at r.t., and the progress of the reaction was followed by

TLC. When full conversion was achieved, Amberlite IRA 120 H⁺was

added until pH 7 and the beads were filtered off. The solvent was

evaporated under vacuum to obtain 21 as a colorless solid (203 mg,

quant.).

¹H NMR (CD₃OD, 500 MHz): δ = 5.93 (dddd, J = 17.3, 10.6, 5.8, 4.9 Hz,

1 H, OCH₂CH=CH₂), 5.31 (ddd, J = 17.3, 3.6, 1.8 Hz, 1 H, OCH₂CH=CH₂),

5.17 (ddd, J = 10.5, 3.2, 1.6 Hz, 1 H, OCH₂CH=CH₂), 4.48 (d, J = 8.4 Hz,

1 H, H1), 4.38 (ddt, J = 13.3, 5.0, 1.7 Hz, 1 H, OCH₂CH=CH₂), 4.11 (ddt,

J = 13.3, 5.8, 1.5 Hz, 1 H, OCH₂CH=CH₂), 3.92 (dd, J = 11.9, 2.3 Hz, 1 H,

H6), 3.77–3.66 (m, 2 H, H2 + H6), 3.40–3.33 (m, 1 H, H4), 3.29 (ddd,

J = 9.7, 5.9, 2.3 Hz, 1 H, H2).

¹³C NMR (CD₃OD, 125 MHz): δ = 174.2 (C=O), 136.0 (OCH₂CH=CH₂),

117.3 (OCH₂CH=CH₂), 102.3 (C1), 78.4 (C5), 76.5 (C3), 72.6 (C4), 71.1

(OCH₂CH=CH₂), 63.2 (C6), 57.8 (C2), 23.3 (NHCOCH₃).

HRMS (ESI): m/z [M + Na]⁺calcd for C₂₉H₄₀NaO₁₈: 699.2112; found:

699.2107.

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₁H₁₉NaO₆: 284.1110; found:

284.1105.

Allyl-β-lactose (25)

NaOMe (5.0 mg, 0.10 mmol) was added in one portion to a solution of

24 (450 mg, 0.67 mmol) in anhydrous MeOH (15 mL). The solution

was stirred at r.t. and the progress of the reaction was followed by

TLC. When full conversion was achieved, Amberlite IRA 120 H⁺was

Allyl-2-acetamido-2-deoxy-β-D-galactopyranose (22)

NaOMe (10 mg, 0.19 mmol) was added in one portion to a solution of

20 (500 mg, 1.29 mmol) in anhydrous MeOH (20 mL). The mixture

was stirred at r.t. and followed by TLC. When full conversion was

J

J. J. Reina et al.

Paper

Synthesis

added until pH 7 and the beads were filtered off. The solvent was

evaporated under vacuum to obtain 25 (254 mg, quant.) as a colorless

solid.

¹H NMR (CD₃OD, 500 MHz): δ = 6.03–5.93 (m, 1 H, OCH₂CH=CH₂),

5.33 (ddd, J = 17.2, 3.6, 1.8 Hz, 1 H, OCH₂CH=CH₂), 5.19–5.14 (m, 2 H,

H1B

+

OCH₂CH=CH₂), 4.37 (ddd, J = 17.2, 3.6, 1.8 Hz, 1 H,

OCH₂CH=CH₂), 4.32 (d, J = 7.8 Hz, 1 H, H1A), 4.15 (ddd, J = 12.9, 6.1,

1.5 Hz, 1 H, OCH₂CH=CH₂), 3.89 (dd, J = 12.2, 2.1 Hz, 1 H, H6B), 3.84–

3.78 (m, 2 H, H6A + H6B), 3.71–3.58 (m, 4 H, H3A + H3B + H4B + H6A),

3.54 (t, J = 9.2 Hz, 1 H, H4A), 3.44 (dd, J = 9.7, 3.7 Hz, 1 H, H2B), 3.40–

3.34 (m, 1 H, H5A), 3.28–3.21 (m, 2 H, H2A + H5B).

¹H NMR (CD₃OD, 500 MHz): δ = 6.09–5.90 (m, 1 H, OCH₂CH=CH₂),

5.35 (ddd, J = 17.3, 3.4, 1.7 Hz, 1 H, OCH₂CH=CH₂), 5.21 (ddd, J = 10.4,

3.4, 1.7 Hz, 1 H,OCH₂CH=CH₂), 4.43–4.38 (m, 1 H, OCH₂CH=CH₂),4.40

(d, J = 7.5 Hz, 1 H, H1B), 4.38 (d, J = 7.8 Hz, 1 H, H1A), 4.19 (ddt,

J = 12.9, 6.1, 1.5 Hz, 1 H, OCH₂CH=CH₂), 3.94 (dd, J = 3.5, 1.7 Hz, 1 H,

H6A), 3.91–3.86 (m, 1 H, H6A), 3.86 (d, J = 3.2 Hz, 1 H, H4B), 3.82 (dd,

J = 11.4, 7.4 Hz, 1 H, H6B), 3.74 (dd, J = 11.4, 7.4 Hz, 1 H, H6B), 3.66–

3.55 (m, 3 H, H3A + H2B + H4B), 3.55–3.50 (m, 2 H, H4A + H3B), 3.43

(ddd, J = 9.5, 4.3, 2.6 Hz, 1 H, H5A), 3.31 (dd, J = 9.0, 7.9 Hz, 1 H, H2A).

¹³C NMR (CD₃OD, 125 MHz):

δ = 135.6 (OCH₂CH=CH₂), 117.5

(OCH₂CH=CH₂), 103.3 (C1A), 102.9 (C1B), 81.2 (C4B), 77.8 (C4A or

C3B), 76.6 (C5A), 75.1 (C3A), 74.7 (C2A), 74.7 (C4A or C3B), 74.1 (C2B),

71.5 (C5B), 71.1 (OCH₂CH=CH₂), 62.7 (C6A or C6B), 62.2 (C6A or C6B).

¹³C NMR (CD₃OD, 125 MHz):

δ

=

136.1 (OCH₂CH=CH₂), 117.9

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₅H₂₆NaO₁₁: 405.1373; found:

(OCH₂CH=CH₂), 105.5 (C1), 103.7 (C1), 81.1, 77.5, 76.9, 75.3, 75.2,

73.0, 71.5, 70.7 (OCH₂CH=CH₂), 62.9 (C6), 62.3 (C6).

405.1368.

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₅H₂₆NaO₁₁: 405.1373; found:

Allyl-Manα1,3[Manα1,6]Man

405.1370.

Allyl-6-O-tert-butyldimethyllsilyl-α-D-mannopyranose (29)

Allyl Per(acetylated) Maltose (27)

Imidazole (0.78 g, 11.44 mmol) and TBDMS-Cl (1.26 g, 8.39 mmol)

were added to a solution of allyl mannose 8 (1.67 g, 7.62 mmol) in

DMF (15 mL). The reaction mixture was stirred overnight at r.t., dilut-

ed with CH₂Cl₂(150 mL) and washed with water (150 mL) and brine

(150 mL). The organic phase was dried over anhydrous MgSO₄, fil-

tered and concentrated under vacuum. The residue was purified by

column chromatography on silica gel (EtOAc/hexane, 1.5:1) to afford

29 (1.99 g, 78%) as a colorless oil.

BF₃·Et₂O (0.9 mL, 7.35 mmol) was added to a cooled (0 °C) solution of

peracetyl-maltose 26 (1.0 g, 1.48 mmol) and allyl alcohol (150 μL,

2.21 mmol) in anhydrous CH₂Cl₂(10 mL). The reaction mixture was

stirred at r.t. for 16 h. The reaction was diluted with CH₂Cl₂(50 mL)

and washed with water (3 × 50 mL), NaHCO₃sat. soln (3 × 50 mL) and

brine solution (50 mL). The organic layer was dried over anhydrous

magnesium sulfate and evaporated to dryness. Finally, the residue

was purified by column chromatography on silica gel (hexane/EtOAc,

1:1) to give 27 (650 mg, 65%) as a colorless solid.

R_f0.63 (hexane/EtOAc, 1:2).

¹H NMR (CDCl₃, 500 MHz): δ = 5.89 (dddd, J = 16.8, 10.4, 6.1, 5.1 Hz,

1 H, OCH₂CH=CH₂), 5.28 (ddd, J = 17.2, 3.2, 1.6 Hz, 1 H, OCH₂CH=CH₂),

5.19 (ddd, J = 10.4, 2.8, 1.4 Hz, 1 H,OCH₂CH=CH₂), 4.85 (d, J = 1.6 Hz,

1 H, H1), 4.18 (ddt, J = 12.9, 5.1, 1.5 Hz, 1 H, OCH₂CH=CH₂), 3.98 (ddt,

J = 12.9, 6.1, 1.4 Hz, 1 H, OCH₂CH=CH₂), 3.93 (dd, J = 3.5, 1.7 Hz, 1 H,

H2), 3.91–3.83 (m, 3 H, H3 + 2 H6), 3.77 (t, J = 9.3 Hz, 1 H, H4), 3.62

(dt, J = 9.5, 5.4 Hz, 1 H, H5), 0.91 (s, 9 H, C(CH₃)₃), 0.10 (s, 6 H, 2CH₃).

R_f0.38 (hexane/EtOAc, 1:1).

¹H NMR (CDCl₃, 500 MHz): δ = 5.84 (dddd, J = 17.0, 10.8, 6.2, 4.9 Hz,

1 H, OCH₂CH=CH₂), 5.40 (d, J = 4.1 Hz, 1 H, H1B), 5.35 (t, J = 10.0 Hz,

1 H, H3B), 5.29–5.23 (m, 1 H, OCH₂CH=CH₂), 5.24 (t, J = 9.0 Hz, 1 H,

H3A), 5.20 (ddd, J = 10.4, 2.8, 1.4 Hz, 1 H, OCH₂CH=CH₂), 5.04 (t,

J = 9.9 Hz, 1 H, H4B), 4.87–4.82 (m, 2 H, H2A + H2B), 4.58 (d,

J = 7.9 Hz, 1 H, H1A), 4.48 (dd, J = 12.1, 2.8 Hz, 1 H, H6A), 4.30 (ddt,

J = 13.2, 5.0, 1.6 Hz, 1 H, OCH₂CH=CH₂), 4.23 (ddd, J = 12.1, 8.2, 4.3 Hz,

2 H, H6A + H6B), 4.09 (ddt, J = 13.2, 6.2, 1.4 Hz, 1 H, OCH₂CH=CH₂),

4.04 (dd, J = 12.4, 2.2 Hz, 1 H, H6B), 4.00 (t, J = 10.0 Hz, 1 H, H4A), 3.96

(ddd, J = 10.3, 4.0, 2.3 Hz, 1 H, H5B), 3.96 (ddd, J = 9.6, 4.5, 2.8 Hz, 1 H,

H5A), 2.14 (s, 3 H, OCOCH₃), 2.09 (s, 3 H, OCOCH₃), 2.08 (OCOCH₃),

2.02 (s, 6 H, OCOCH₃), 2.00 (s, 3 H, OCOCH₃), 1.99 (s, 3 H, OCOCH₃).

¹³C NMR (CDCl₃, 125 MHz):

δ = 134.0 (OCH₂CH=CH₂), 117.9

(OCH₂CH=CH₂), 99.1 (C1), 70.8, 70.9, 72.1, 71.1 (C2, C3, C4, C5), 68.4

(OCH₂CH=CH₂), 65.1 (C6), 26.3 (C(CH₃)₃), 18.6 (C(CH₃)₃), –5.1 (CH₃),

–5.0 (CH₃).

HRMS (ESI): m/z [M + Na]⁺calcd for C₂₅H₃₄NaO₆Si: 481.2022; found:

481.2017.

¹³C NMR (CDCl₃, 125 MHz): δ = 170.9 (2 × C=O), 170.9 (C=O), 170.6

(C=O), 170.3 (C=O), 170.0 (C=O), 169.8 (C=O), 133.7 (OCH₂CH=CH₂),

118.1 (OCH₂CH=CH₂), 99.4 (C1A), 95.9 (C1B), 75.9 (C3A), 73.2 (C4A),

72.6 (C5A), 72.5 (C2A or C2B), 70.0 (C2A or C2B + OCH₂CH=CH₂), 69.8

(C3B), 68.9 (C5B), 68.5 (C4B), 63.2 (C6A), 62.0 (C6B), 21.3 (OCOCH₃),

21.3 (OCOCH₃), 21.2 (OCOCH₃), 21.1 (OCOCH₃), 21.0 (OCOCH₃), 21.0

(OCOCH₃), 20.9 (OCOCH₃).

Allyl-2-O-acetyl-4-O-benzoyl-6-O-tert-butyldimethylsilyl-α-D-

mannopyranose (30)

Camphorsulfonic acid (0.20 g, 0.84 mmol) and trimethyl orthoacetate

(1.6 mL, 12.54 mmol) were sequentially added to a solution of 29

(1.40 g, 4.18 mmol) in CH₃CN (70 mL) and the reaction mixture was

stirred at r.t. for 1 h. The reaction was then quenched with Et₃N (650

μL) and the solvent was evaporated. The crude material was dissolved

in CH₂Cl₂(60 mL) and Bz₂O (1.89 g, 8.36 mmol), Et₃N (2.33 mL, 16.72

mmol) and 4-DMAP (50 Mg, 0.42 mmol) were sequentially added.

The reaction mixture was stirred at r.t. for 1 h. The solvent was evapo-

rated and the crude residue was diluted with EtOAc (150 mL). The or-

ganic phase was washed with 1 M HCl (150 mL), sat. NaHCO₃(150 mL)

and water (150 mL), the organic phase was dried over anhydrous

MgSO₄and the solvent was evaporated. The residue was purified by

flash chromatography on silica gel (hexane/EtOAc, 2.5:1) to obtain 30

(1.31 g, 66%) as a colorless oil.

HRMS (ESI): m/z [M + Na]⁺calcd for C₂₉H₄₀NaO₁₈: 699.2112; found:

699.2106.

Allyl β-D-Maltose (28)

NaOMe (6.0 mg, 0.12 mmol) was added in one portion to a solution of

27 (480 mg, 0.71 mmol) in anhydrous MeOH (15 mL). The solution

was stirred at r.t. and the progress of the reaction was followed by

TLC. When full conversion was achieved, Amberlite IRA 120 H⁺was

added until pH 7 and the beads were filtered off. The solvent was

evaporated under vacuum to obtain 28 (271 mg, quant.) as a colorless

solid.

R_f0.20 (hexane/EtOAc, 2:1).

K

J. J. Reina et al.

Paper

Synthesis

¹H NMR (CDCl₃, 500 MHz): δ = 8.05 (d, J = 3.4 Hz, 2 H, H_Arortho), 7.59

(t, J = 7.5 Hz, 1 H, H_Arpara), 7.46 (t, J = 7.8 Hz, 2 H, H_Armeta), 5.99–

5.87 (m, 1 H, OCH₂CH=CH₂), 5.36 (t, J = 9.7 Hz, 1 H, H4), 5.34 (ddd,

J = 17.1, 3.4, 1.7 Hz, 1 H, OCH₂CH=CH₂), 5.24 (ddd, J = 10.4, 2.8, 1.4 Hz,

1 H, OCH₂CH=CH₂), 5.12 (dd, J = 3.6, 1.7 Hz, 1 H, H2), 4.95 (d,

J = 1.6 Hz, 1 H, H1), 4.27–4.23 (m, 1 H, H3), 4.22 (m, 1 H,

OCH₂CH=CH₂), 4.04 (m, 1 H, OCH₂CH=CH₂), 3.94 (ddd, J = 10.0, 4.7,

2.8 Hz, 1 H, H5), 3.82–3.75 (m, 2 H, 2 H6), 2.16 (s, 3 H, CO(CH₃)), 0.86

(s, 9 H, C(CH₃)₃), –0.01 (d, J = 14.5 Hz, 6 H, 2 CH₃).

¹³C NMR (CDCl₃, 125 MHz): δ = 170.9 (C=O), 167.3 (C=O), 133.8

(OCH₂CH=CH₂+ C_Ar), 130.2 (C_Ar), 129.9 (C_Ar), 128.8 (C_Ar), 118.1

(OCH₂CH=CH₂), 96.7 (C1), 73.1 (C2), 71.6 (C5), 70.9 (C4), 69.4 (C3),

68.7 (OCH₂CH=CH₂), 62.8 (C6), 26.2 (C(CH₃)₃), 21.4 (CO(CH₃)), 18.6

(C(CH₃)₃), –5.1 (CH₃), –5.0 (CH₃).

1.4 Hz, 2 H, 2 H_Ar), 7.61–7.47 (m, 6 H, 6 H_Ar), 7.46–7.20 (m, 21 H,

21 H_Ar), 6.10 (t, J = 10.1 Hz, 1 H, H4B), 6.04 (t, J = 10.1 Hz, 1 H, H4C),

6.00–5.90 (m, 2 H, OCH₂CH=CH₂+ H3B), 5.80–5.71 (m, 3 H, H2B + H4A

+ H3C), 5.52 (dd, J = 3.5, 1.7 Hz, 1 H, H2A), 5.43 (ddd, J = 17.3, 3.0,

1.5 Hz, 1 H, OCH₂CH=CH₂), 5.39 (dd, J = 3.3, 1.8 Hz, 1 H, H2C), 5.32–

5.28 (m, 2 H, OCH₂CH=CH₂+ H1C), 5.12 (d, J = 1.8 Hz, 1 H, H1B), 5.00

(d, J = 1.6 Hz, 1 H, H1A), 4.70 (dd, J = 12.2, 2.3 Hz, 1 H, H6C), 4.65–4.59

(m, 3 H, H3A + H5C + H6C), 4.55 (ddd, J = 10.2, 4.5, 2.5 Hz, 1 H, H5B),

4.51 (dd, J = 12.2, 4.1 Hz, 1 H, H6B), 4.41 (dd, J = 12.1, 4.5 Hz, 1 H,

H6B), 4.34 (ddt, J = 12.9, 5.4, 1.4 Hz, 1 H, OCH₂CH=CH₂), 4.21 (ddd,

J = 10.3, 6.5, 2.1 Hz, 1 H, H5A), 4.16 (ddt, J = 12.8, 6.2, 1.3 Hz, 1 H,

OCH₂CH=CH₂), 4.10 (dd, J = 11.2, 6.8 Hz, 1 H, H6A), 3.73 (dd, J = 10.8,

2.2 Hz, 1 H, H6A), 2.36 (s, 3 H, COCH₃).

¹³C NMR (CDCl₃, 125 MHz): δ = 170.8 (C=O), 166.2 (C=O), 166.1 (C=O),

165.5 (C=O), 165.4 (C=O), 165.3 (C=O), 165.2 (C=O), 165.0 (C=O), 164.5

(C=O), 133.4 (C_Ar), 133.4 (C_Ar), 133.4 (C_Ar), 133.2 (C_Ar), 133.1 (C_Ar),

133.1 (C_Ar), 133.0 (C_Ar), 129.9 (C_Ar), 129.9 (C_Ar), 129.9 (C_Ar), 129.8 (C_Ar),

129.8 (C_Ar), 129.7 (C_Ar), 129.7 (C_Ar), 129.7 (C_Ar), 129.3 (C_Ar), 129.2 (C_Ar),

129.2 (C_Ar), 129.1 (C_Ar), 129.1 (C_Ar), 129.0 (C_Ar), 128.8 (C_Ar), 128.6 (C_Ar),

128.5 (C_Ar), 128.4 (C_Ar), 128.4 (C_Ar), 128.3 (C_Ar), 128.2 (C_Ar), 118.7

(OCH₂CH=CH₂), 99.2 (C1C), 97.5 (C1B), 96.5 (C1A), 74.4, 71.1 (C2A),

70.4, 70.2 (C2C), 70.0, 69.8, 69.7, 69.22, 69.1, 68.9, 68.6

(OCH₂CH=CH₂), 66.8, 66.6, 62.8 (C6), 21.1 (COCH₃).

HRMS (ESI): m/z [M + Na]⁺calcd for C₃₄H₄₀NaO₈Si: 627.2390; found:

627.2388.

Allyl-2-O-acetyl-4-O-benzoyl-α-D-mannopyranose (31)

AcOH (1.2 mL) and TBAF (1 M in THF, 2.17 mL, 2.17 mmol) were se-

quentially added to a solution of 30 (1.05 g, 2.18 mmol) in THF (16

mL) at 0 °C. The reaction mixture was allowed to warm to r.t. and

stirred overnight. The solvent was evaporated and the residue was

purified by flash chromatography on silica gel (hexane/EtOAc, 1:1) to

afford 31 (601 mg, 75%) as a colorless oil.

HRMS (ESI): m/z [M + Na]⁺calcd for C₈₆H₇₄NaO₂₆: 1545.4366; found:

1545.4361

R_f0.38 (hexane/EtOAc, 1:1).

¹H NMR (CDCl₃, 500 MHz): δ = 8.06 (d, J = 8.2 Hz, 2 H, C_Arortho), 7.60

(t, J = 7.5 Hz, 1 H, C_Arpara), 7.46 (t, J = 7.9 Hz, 2 H, C_Armeta), 5.97–5.87

(m, 1 H, OCH₂CH=CH₂), 5.36–5.30 (m, 2 H, OCH₂CH=CH₂+ H4), 5.25

(ddd, J = 10.4, 2.8, 1.4 Hz, 1 H, OCH₂CH=CH₂), 5.17 (dd, J = 3.7, 1.7 Hz,

1 H, H2), 4.98 (d, J = 1.7 Hz, 1 H, H1), 4.37–4.31 (m, 1 H, H3), 4.21 (ddt,

J = 12.9, 5.4, 1.5 Hz, 1 H, OCH₂CH=CH₂), 4.05 (ddt, J = 12.9, 6.1, 1.4 Hz,

1 H, OCH₂CH=CH₂), 3.90 (ddd, J = 10.1, 4.7, 2.8 Hz, 1 H, H5), 3.76 (d,

J = 12.7 Hz, 1 H, H6), 3.70 (dd, J = 12.6, 4.2 Hz, 1 H, H6), 2.18 (s, 3 H,

CO(CH₃)).

¹³C NMR (CDCl₃, 125 MHz): δ = 171.0 (C=O), 167.7 (C=O), 134.1 (C_Ar),

133.6 (OCH₂CH=CH₂), 130.3 (C_Ar), 129.4 (C_Ar), 128.9 (C_Ar), 118.4

(OCH₂CH=CH₂), 97.1 (C1), 72.92 (C2), 70.9 (C5), 70.6 (C4), 69.1

(OCH₂CH=CH₂), 68.8 (C3), 61.8 (C6), 21.41 (CO(CH₃)).

Allyl-O-(α-D-mannopyranosyl)-(1-3)-O-[α-D-mannopyranosyl-(1-

6)]-α-D-mannopyranose (34)

NaOMe (50 mg, 0.93 mmol) was added in one portion to a solution of

compound 33 (229 mg, 0.15 mmol) in MeOH/toluene (4:1, 7.5 mL)

and the reaction mixture was stirred at r.t. for 1 h. Aqueous NaOH

(1 M, 3 mL) was then added and the reaction mixture was heated at

50 °C and stirred for 7 h. After neutralization with Amberlite IRA 120

H⁺, the solution was filtered and concentrated. The crude material

was diluted with water (10 mL) and washed with toluene (2 × 10 mL),

the aqueous phase was separated and the water was evaporated to af-

ford 34 (70 mg, 90%) as a colorless amorphous solid.

¹H NMR (D₂O, 500 MHz): δ = 5.85 (dddd, J = 17.1, 10.4, 6.2, 5.4 Hz, 1 H,

OCH₂CH=CH₂), 5.23 (ddd, J = 17.2, 3.2, 1.6 Hz, 1 H, OCH₂CH=CH₂), 5.15

(ddd, J = 10.4, 2.6, 1.3 Hz, 1 H, OCH₂CH=CH₂), 4.98 (d, J = 1.7 Hz, 1 H,

H1), 4.77 (d, J = 1.8 Hz, 1 H, H1), 4.75 (d, J = 1.8 Hz, 1 H, H1), 4.10 (ddt,

J = 12.9, 5.4, 1.5 Hz, 1 H, OCH₂CH=CH₂), 3.98 (dd, J = 2.5, 1.7 Hz, 1 H,

H2), 3.96 (ddd, J = 6.7, 2.6, 1.3 Hz, 1 H, OCH₂CH=CH₂), 3.94 (dd, J = 3.4,

1.7 Hz, 1 H, H2), 3.88 (dd, J = 7.0, 4.4 Hz, 1 H, H6), 3.86 (dd, J = 3.5,

1.7 Hz, 1 H, H2), 3.79–3.73 (m, 5 H, H3 + 2 H6), 3.71 (dd, J = 8.9,

3.4 Hz, 2 H), 3.67–3.57 (m, 4 H, 3 H6), 3.56–3.50 (m, 3 H).

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₈H₂₂NaO₈: 389.1212; found:

389.1205.

Allyl-O-(2,3,4,6-tetra-O-benzoyl-α-D-mannopyranosyl)-(1-3)-O-

[2,3,4,6-tetra-O-benzoyl-α-D-mannopyranosyl-(1-6)]-2-O-acetyl-

4-O-benzoyl-α-D-mannopyranose (33)

A mixture of acceptor 31 (58 mg, 0.16 mmol) and donor 32 (286 mg,

0.38 mmol) was co-evaporated from toluene three times. Powdered

and activated 4 Å molecular sieves were added, and the mixture was

kept under vacuum for a few hours and then dissolved in anhydrous

CH₂Cl₂(5 mL). The mixture was cooled to 0 °C for 15 min, followed by

the addition of TMSOTf (8.5 μL, 0.047 mmol), and stirred for 30 min at

0 °C. The reaction was quenched by the addition of Et₃N, filtered

through Celite and dried under vacuum. The crude was purified by

flash column chromatography on silica gel (hexane/EtOAc, 1.75:1) to

obtain 33 (254 mg, quant.) as a colorless solid.

¹³C NMR (D₂O, 125 MHz):

δ = 133.1 (OCH₂CH=CH₂), 118.2

(OCH₂CH=CH₂), 102.3 (C1), 99.2 (C1), 99.1 (C1), 78.4, 73.2, 72.6, 71.0,

70.5, 70.2, 69.9 (C2), 69.8 (C2), 69.5 (C2), 68.2 (OCH₂CH=CH₂), 66.6,

66.6, 65.6, 65.1 (C6), 60.9 (C6), 60.8 (C6).

HRMS (ESI): m/z [M + Na]⁺calcd for C₂₁H₃₆NaO₁₆: 567.1901; found:

567.1895.

Oxime Neoglycoconjugates; General Procedure C

Ozone was bubbled through a solution of allyl glycoside 16 (250 mg)

in MeOH (75 mL) at –78 °C until the solution turned blue (ca. 25 min).

The solution was purged under N₂flow to remove the excess of ozone,

and dimethyl sulfide (1 mL) was added. After a few minutes, nitrogen

was again passed through the solution, which was then allowed to

warm to r.t. The solvent was removed under reduced pressure to af-

R_f0.56 (hexane/EtOAc, 1:2).

¹H NMR (CDCl₃, 500 MHz): δ = 8.14 (dd, J = 8.3, 1.4 Hz, 2 H, 2 H_Ar),

8.10–8.07 (m, 2 H, 2 H_Ar), 8.06–8.04 (m, 2 H, 2 H_Ar), 8.04–8.02 (m, 2 H,

2 H_Ar), 8.02–7.99 (m, 2 H, 2 H_Ar), 7.99–7.96 (m, 2 H, 2 H_Ar), 7.83 (dd,

J = 8.4, 1.4 Hz, 2 H, 2 H_Ar), 7.81–7.78 (m, 2 H, 2 H_Ar), 7.76 (dd, J = 8.4,

L

J. J. Reina et al.

Paper

Synthesis

ford glycosyl aldehydes 29–39 (quant.) as a colorless oil. O-Benzylhy-

droxylamine hydrochloride (1.1 equiv) was then added to the solution

of the corresponding glycosyl aldehydes (10 mg, 1 equiv) in H₂O

(1 mL). The mixture was stirred at 40 °C for 30 min and the final ox-

ime was purified by semipreparative HPLC to obtain the Z/E mixture

of neoglycoconjugates 47–58.

(E/Z)-β-D-Glucopyranosyl Acetaldehyde O-Benzyl Oxime (49)

According to Procedure C, compound 49 (12.2 mg, 83%) was obtained

as a colorless solid after HPLC purification (t_R8.5 min).

¹H NMR (CD₃OD, 500 MHz): δ = 7.63–7.54 (t, J = 5.5 Hz, 1 H, OCH₂-

CH=N-O E isomer), 7.43–7.24 (m, 10 H, 5 H_ArE isomer + 5 H_ArZ iso-

mer), 7.00 (t, J = 3.6 Hz, 1 H, OCH₂-CH=N-O E isomer), 5.10 (s, 2 H,

CH_2BnZ isomer), 5.07 (s, 2 H, CH_2BnZ isomer), 4.67 (dd, J = 16.6, 3.5 Hz,

(E/Z)-α-D-Mannopyranosyl Acetaldehyde O-Benzyl Oxime (47)

1 H, OCH₂CH=N-O

Z isomer), 4.55 (dd, J = 16.6, 3.8 Hz, 1 H,

According to Procedure C, compound 47 (12.5 mg, 85%) was obtained

as a colorless solid after HPLC purification (t_R8.5 min).

¹H NMR (CD₃OD, 500 MHz): δ = 7.56 (dd, J = 6.3, 5.3 Hz, 1 H,

OCH₂CH=N-O Z isomer), 4.41 (dd, J = 12.9, 5.3 Hz, 1 H, OCH₂CH=N-O E

isomer), 4.30 (d, J = 7.9 Hz, 1 H, H1 Z isomer), 4.29 (d, J = 7.9 Hz, 1 H,

H1 E isomer), 4.28 (dd, J = 13.1, 6.2 Hz, 1 H, OCH₂CH=N-O E isomer),

3.86 (ddd, J = 11.9, 3.7, 2.3 Hz, 2 H, H6 Z and E isomer), 3.68 (dd,

J = 12.0, 5.5 Hz, 2 H, H6 Z and E isomer), 3.40–3.16 (m, 8 H, H2 + H3 +

H4 + H5 Z and E isomer).

¹³C NMR (CD₃OD, 125 MHz): δ = 152.3 (OCH₂-CH=N-O Z isomer),

149.6 (OCH₂-CH=N-O E isomer), 139.5 (C_Ar), 129.8 (C_Ar), 129.6 (C_Ar),

129.5 (C_Ar), 129.3 (C_Ar), 105.0 (C1 Z isomer), 104.4 (C1 E isomer), 78.4

(C5 Z and E isomer), 77.7 (CH_2BnZ isomer), 77.3 (CH_2BnE isomer), 75.4

(C2 Z and E isomer), 71.9 (C4 Z and E isomer), 67.5 (OCH₂CH=N-O E

isomer), 65.4 (OCH₂CH=N-O Z isomer), 63.1 (C6 Z and E isomer).

OCH₂CH=N-O E isomer), 7.37–7.27 (m, 10 H, 5 H_ArE isomer + 5 H_Ar

Z

isomer), 6.93 (t, J = 3.7 Hz, 1 H, OCH₂CH=N-O Z isomer), 5.10 (s, 2 H,

CH_2BnZ isomer), 5.08 (s, 2 H, CH_2BnE isomer), 4.82 (d, J = 1.7 Hz, 1 H,

H1 E isomer), 4.80 (d, J = 1.7 Hz, 1 H, H1 Z isomer), 4.54 (dd, J = 16.4,

3.6 Hz, 1 H, OCH₂CH=N-O Z isomer), 4.41 (dd, J = 16.4, 3.9 Hz, 1 H,

OCH₂CH=N-O Z isomer), 4.26 (dd, J = 12.7, 5.4 Hz, 1 H, OCH₂CH=N-O E

isomer), 4.15 (dd, J = 12.7, 6.3 Hz, 1 H, OCH₂CH=N-O E isomer), 3.86–

3.84 (m, 3 H, H2 + H6 Z isomer), 3.84–3.81 (m, 1 H, H2 + H6 E isomer),

3.75–3.67 (m, 4 H, H3 + H6 Z and E isomer), 3.66–3.61 (m, 2 H, H4 Z

and E isomer), 3.56–3.50 (m, 2 H, H5 Z and E isomer).

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₅H₂₁NNaO₇: 350.1216; found:

¹³C NMR (CD₃OD, 125 MHz): δ = 151.5 (OCH₂-CH=N-O Z isomer),

148.9 (OCH₂-CH=N-O E isomer), 139.4 (C_Ar), 139.4 (C_Ar), 129.8 (C_Ar),

129.6 (C_Ar), 129.5 (C_Ar), 129.3 (C_Ar), 129.3 (C_Ar), 102.3 (C1 Z isomer),

101.8 (C1 E isomer), 77.7 (CH_2BnZ isomer), 77.4 (CH_2BnE isomer), 75.5

(C5 Z isomer), 75.4 (C5 E isomer), 72.9 (C3 isomer and Z isomer), 72.4

(C2 isomer and Z isomer), 69.0 (C4 Z isomer), 68.9 (C4 E isomer), 65.5

(OCH₂CH=N-O E isomer), 63.3 (OCH₂CH=N-O Z isomer), 63.3 (C6 Z and

E isomer).

350.1213.

(E/Z)-α-D-Galactopyranosyl Acetaldehyde O-Benzyl Oxime (50)

According to Procedure C, compound 50 (11.8 mg, 80%) was obtained

as a colorless solid after HPLC purification (t_R8.5 min).

¹H NMR (CD₃OD, 500 MHz): δ = 7.61 (t, J = 5.7 Hz, 1 H, OCH₂CH=N-O E

isomer), 7.40 (m, 10 H, 5 H_ArE isomer + 5 H_ArZ isomer), 7.02 (t,

J = 3.7 Hz, 1 H, OCH₂CH=N-O Z isomer), 5.10 (s, 2 H, CH_2BnE isomer),

5.08 (s, 2 H, CH_2BnZ isomer), 4.88 (s, 1 H, J = 4.0 Hz, H1 E isomer or H1

Z isomer), 4.85 (s, J = 4.0 Hz, 2 H, H1 E isomer or H1 Z isomer), 4.55

(dd, J = 16.5, 3.5 Hz, 1 H, OCH₂CH=N-O Z isomer), 4.43 (dd, J = 16.5,

3.8 Hz, 1 H, OCH₂CH=N-O Z isomer), 4.29 (dd, J = 12.9, 5.4 Hz, 1 H,

OCH₂CH=N-O E isomer), 4.18 (dd, J = 13.0, 6.1 Hz, 1 H, OCH₂CH=N-O E

isomer), 3.91–3.88 (m, 2 H, H4 E isomer+ H4 Z isomer), 3.85–3.65 (m,

10, H2 + H3 + H5 + 2 H6 E and Z isomer).

¹³C NMR (CD₃OD, 125 MHz): δ = 151.9 (OCH₂-CH=N-O Z isomer),

149.4 (OCH₂-CH=N-O E isomer), 139.4 (C_Ar), 129.8 (C_Ar), 129.8 (C_Ar),

129.6 (C_Ar), 129.5 (C_Ar), 129.3 (C_Ar), 129.3 (C_Ar), 101.3 (C1 E isomer or Z

isomer), 100.8 (C1 E isomer or Z isomer), 77.8, 77.4, 73.3, 73.1, 71.8,

71.5, 70.5, 66.1 (OCH₂CH=N-O E isomer), 64.0 (OCH₂CH=N-O Z iso-

mer), 63.2, 63.1.

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₅H₂₁NNaO₇: 350.1216; found:

350.1213.

(E/Z)-α-D-Glucopyranosyl Acetaldehyde O-Benzyl Oxime (48)

According to Procedure C, compound 48 (11.8 mg, 80%) was obtained

as a colorless solid after HPLC purification (t_R8.5 min).

¹H NMR (CD₃OD, 500 MHz): δ = 7.62 (dd, J = 6.2, 5.4 Hz, 1 H, OCH₂-

CH=N-O E isomer), 7.39–7.28 (m, 10 H, 5 H_ArE isomer + 5 H_ArZ iso-

mer), 7.02 (t, J = 3.7 Hz, 1 H, OCH₂-CH=N-O Z isomer), 5.12 (s, 2 H,

CH_2BnZ isomer), 5.09 (s, 2 H, CH_2BnZ isomer), 4.86 (d, J = 4.0 Hz, 1 H,

H1 E isomer), 4.85 (d, J = 4.0 Hz, 1 H, H1 Z isomer), 4.58 (dd, J = 16.5,

3.6 Hz, 1 H, OCH₂CH=N-O Z isomer), 4.45 (dd, J = 16.5, 3.8 Hz, 1 H,

OCH₂CH=N-O Z isomer), 4.31 (dd, J = 12.9, 5.4 Hz, 1 H, OCH₂CH=N-O E

isomer), 4.20 (dd, J = 12.9, 6.2 Hz, 1 H, OCH₂CH=N-O E isomer), 3.83

(dt, J = 11.9, 2.4 Hz, 2 H, H6 Z and E isomer), 3.73–3.63 (m, 4 H, H3 +

H6 Z and E isomer), 3.60 (ddd, J = 10.1, 5.6, 2.3 Hz, 2 H, H5 Z and E iso-

mer), 3.45 (dd, J = 7.6, 3.8 Hz, 1 H, H2 Z or E isomer), 3.43 (dd, J = 7.7,

3.8 Hz, 1 H, H2 Z or E isomer), 3.35–3.30 (m, 2 H, H4 Z and E isomer).

¹³C NMR (CD₃OD, 125 MHz): δ = 151.8 (OCH₂-CH=N-O Z isomer),

149.2 (OCH₂-CH=N-O E isomer), 139.4 (C_Ar), 129.8 (C_Ar), 129.6 (C_Ar),

129.5 (C_Ar), 129.3 (C_Ar), 129.3 (C_Ar), 101.0 (C1 E isomer), 100.5 (C1 Z

isomer), 77.7 (CH_2BnZ isomer),, 77.4 (CH_2BnE isomer), 75.4 (C3 Z and E

isomer), 74.5 (C4 Z isomer), 74.4 (C5 E isomer), 73.8 (C2 E isomer),

73.8 (C2 Z isomer), 72.2 (C4 Z isomer), 72. 1 (C4 E isomer), 66.1

(OCH₂CH=N-O E isomer), 63.8 (OCH₂CH=N-O Z isomer), 63.0 (C6 Z

isomer), 63.0 (C6 E isomer).

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₅H₂₁NNaO₇: 350.1216; found:

350.1210.

(E/Z)-β-D-Galactopyranosyl Acetaldehyde O-Benzyl Oxime (51)

According to Procedure C, compound 51 (13.3 mg, 90%) was obtained

as a colorless solid after HPLC purification (t_R8.5 min).

¹H NMR (CD₃OD, 500 MHz): δ = 7.59 (dd, J = 6.2, 5.3 Hz, 1 H, OCH₂-

CH=N-O E isomer), 7.38–7.27 (m, 10 H, 5 H_ArE isomer + 5 H_ArZ iso-

mer), 7.00 (t, J = 3.6 Hz, 1 H, OCH₂-CH=N-O E isomer), 5.09 (s, 2 H,

CH_2BnZ isomer), 5.07 (s, 2 H, CH_2BnE isomer), 4.67 (dd, J = 16.6, 3.5 Hz,

1 H, OCH₂CH=N-O

Z isomer), 4.55 (dd, J = 16.6, 3.7 Hz, 1 H,

OCH₂CH=N-O Z isomer), 4.41 (dd, J = 12.9, 5.2 Hz, 1 H, OCH₂CH=N-O E

isomer), 4.31–4.24 (m, 3 H, OCH₂CH=N-O E isomer + H1 E and Z iso-

mer), 4.01–3.95 (m, 2 H, H5 Z and E isomer), 3.85 (dd, J = 3.4, 1.5 Hz,

1 H, H4 E isomer), 3.84 (dd, J = 3.4, 1.5 Hz, 1 H, H4 Z isomer), 3.80–

3.70 (m, 3 H, 3 H6), 3.67–3.61 (m, 1 H, H6), 3.58–3.44 (m, 4 H, H2 +

H3 Z and E isomer).

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₅H₂₁NNaO₇: 350.1216; found:

350.1210.

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J. J. Reina et al.

Paper

Synthesis

¹³C NMR (CD₃OD, 125 MHz): δ = 152.4 (OCH₂-CH=N-O Z isomer),

149.7 (OCH₂-CH=N-O E isomer), 139.5 (C_Ar), 129.8 (C_Ar), 129.8 (C_Ar),

129.6 (C_Ar), 129.5 (C_Ar), 129.5 (C_Ar), 129.3 (C_Ar), 129.3 (C_Ar), 105.6 (C1 Z

isomer), 104. 9 (C1 E isomer), 85.0, 83.7, 77.7 (CH_2BnZ isomer), 77.3

(CH_2BnZ isomer), 77.2 (C3 Z or E isomer), 77.8 (C5 Z or E isomer), 75.3

(C5 Z or E isomer), 72.8, 70.7 (C4 Z or E isomer), 70.7 (C4 Z or E iso-

mer), 67.5 (OCH₂CH=N-O E isomer), 65.4 (OCH₂CH=N-O Z isomer),

62.9 (C6 Z and E isomer).

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₅H₂₁NNaO₆: 334.1267; found:

334.1262.

(E/Z)-2-Acetamido-2-deoxy-β-D-glucopyranosyl Acetaldehyde O-

Benzyl Oxime (54)

According to Procedure C, compound 54 (12.6 mg, 90%) was obtained

as a colorless solid after HPLC purification (t_R8.5 min).

¹H NMR (CD₃OD, 500 MHz): δ = 7.52 (dd, J = 6.4, 5.4 Hz, 1 H, OCH₂-

CH=N-O E isomer), 7.38–7.27 (m, 10 H, 5 H_ArE isomer + 5 H_ArZ iso-

mer), 6.90 (t, J = 3.6 Hz, 1 H, OCH₂-CH=N-O Z isomer), 5.09 (s, 2 H,

CH_2BnZ isomer), 5.06 (s, 2 H, CH_2BnE isomer), 4.61 (dd, J = 16.5, 3.5 Hz,

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₅H₂₁NNaO₇: 350.1216; found:

350.1212.

(E/Z)-α-L-Fucopyranosyl Acetaldehyde O-Benzyl Oxime (52)

1 H, OCH₂CH=N-O

OCH₂CH=N-O Z isomer), 4.46 (d, J = 8.4 Hz, 1 H, H1 E isomer), 4.44 (d,

J = 8.4 Hz, 1 H, H1 isomer), 4.34 (dd, J = 12.8, 5.4 Hz, 1 H,

Z isomer), 4.49 (dd, J = 16.6, 3.8 Hz, 1 H,

According to Procedure C, compound 52 (13.7 mg, 85%) was obtained

as a colorless solid after HPLC purification (t_R8.3 min).

Z

OCH₂CH=N-O E isomer), 4.23 (dd, J = 12.8, 6.4 Hz, 1 H, OCH₂CH=N-O E

isomer), 3.88 (dt, J = 12.0, 2.6 Hz, 2 H, H6 Z and E isomer), 3.77–3.61

(m, 4 H, H4 + H6 Z and E isomer), 3.46 (dd, J = 10.3, 8.7 Hz, 2 H, H4 Z

and E isomer), 3.38–3.34 (m, 2 H, H4 Z and E isomer), 3.27 (tdd,

¹H NMR (CD₃OD, 500 MHz): δ = 7.58 (t, J = 5.7 Hz, 1 H, OCH₂CH=N-O E

isomer), 7.38–7.26 (m, 10 H, E isomer + 5 H_ArZ isomer), 6.97 (t,

J = 3.7 Hz, 1 H, OCH₂CH=N-O Z isomer), 5.10 (s, 2 H, CH_2BnZ isomer),

5.07 (s, 2 H, CH_2BnE isomer), 4.82 (d, J = 3.1 Hz, 1 H, H1 E isomer), 4.78

(d, J = 3.1 Hz, 1 H, H1 Z isomer), 4.48 (dd, J = 16.4, 3.7 Hz, 1 H,

OCH₂CH=N-O Z isomer), 4.38 (dd, J = 16.4, 3.8 Hz, 1 H, OCH₂CH=N-O Z

isomer), 4.22 (dd, J = 12.9, 5.6 Hz, 1 H, OCH₂CH=N-O E isomer), 4.16

(dd, J = 12.9, 6.2 Hz, 1 H, OCH₂CH=N-O E isomer), 3.96–3.90 (m, 2 H,

H5 E and Z isomer), 3.77–3.72 (m, 4 H, H2 + H3 E and Z isomer), 3.68–

3.66 (m, 2 H, H4 E and Z isomer), 1.22 (d, J = 5.6 Hz, 3 H, H6 Z isomer),

1.21 (d, J = 6.7 Hz, 3 H, H6 E isomer).

¹³C NMR (CD₃OD, 125 MHz): δ = 151.4 (OCH₂-CH=N-O Z isomer),

148.9 (OCH₂-CH=N-O E isomer), 139.0 (C_Ar), 129.4 (C_Ar), 129.4 (C_Ar),

129.3 (C_Ar), 129.1 (C_Ar), 129.0 (C_Ar), 128.9 (C_Ar), 100.9 (C1 Z isomer),

100.6 (C1 E isomer), 77.4 (CH_2BnZ isomer), 77.0 (CH_2BnE isomer), 73.5

(C4 E or Z isomer), 71.6 (C2 or C3 E isomer), 71.5 (C2 or C3 Z isomer),

69.9 (C2 or C3 Z isomer), 69.8 (C2 or C3 E isomer), 67.9 (C6 Z isomer),

67.9 (C6 E isomer), 65.9 (OCH₂CH=N-O E isomer), 63.4 (OCH₂CH=N-O

Z isomer), 16.7 (C6 Z isomer), 16.7 (C6 E isomer).

J = 9.9, 5.7, 2.3 Hz, 2 H, H5 Z and E isomer), 2.00 (s, 3 H, NHCOCH₃

isomer), 1.98 (s, 3 H, NHCOCH₃E isomer).

Z

¹³C NMR (CD₃OD, 125 MHz): δ = 174.3 (C=O), 174.3 (C=O), 152.16

(OCH₂-CH=N-O Z isomer), 149.36 (OCH₂-CH=N-O E isomer), 139.4

(C_Ar), 129.8 (C_Ar), 129.7 (C_Ar), 129.5 (C_Ar), 129.3 (C_Ar), 129.3 (C_Ar), 103.1

(C1 E isomer), 102.5 (C1 E isomer), 78.5 (C5 Z isomer), 78.5 (C5 E iso-

mer), 77.7 (CH_2BnZ isomer), 77.4 (CH_2BnE isomer), 76.4 (C2 Z and E

isomer), 72.4 (C4 Z and E isomer), 67.2 (OCH₂CH=N-O E isomer), 65.1

(OCH₂CH=N-O Z isomer), 63.1 (C6 E isomer), 63.1 (C6 Z isomer), 57.6

(C4 E isomer), 57.6 (C4 Z isomer), 23.4 (NHCOCH₃).

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₇H₂₄N₂NaO₇: 391.1481; found:

391.1477.

(E/Z)-2-Acetamido-2-deoxy-β-D-galactopyranosyl Acetaldehyde O-

Benzyl Oxime (55)

HRMS (ESI): m/z [M

+

Na]⁺calcd for C₁₅H₂₁NNaO₆: 334.1267;

According to Procedure C, compound 55 (11.6 mg, 83%) was obtained

as a colorless solid after HPLC purification (t_R8.5 min).

found:334.1263.

¹H NMR (CD₃OD, 500 MHz): δ = 7.51 (dd, J = 6.4, 5.4 Hz, 1 H,

(E/Z)-β-L-Fucopyranosyl Acetaldehyde O-Benzyl Oxime (53)

OCH₂CH=N-O E isomer), 7.40–7.23 (m, 10 H, 5 H_ArE isomer + 5 H_Ar

Z

According to Procedure C, compound 53 (14.5 mg. 90%) was obtained

as a colorless solid after HPLC purification (t_R8.3 min).

isomer), 6.90 (t, J = 3.6 Hz, 1 H, OCH₂CH=N-O Z isomer), 5.09 (s, 2 H,

CH_2BnZ isomer), 5.06 (s, 2 H, CH_2BnE isomer), 4.62 (dd, J = 16.6, 3.4 Hz,

1 H, OCH₂CH=N-O

OCH₂CH=N-O Z isomer), 4.43 (d, J = 8.4 Hz, 1 H, H1 E isomer), 4.42 (d,

J = 8.4 Hz, 1 H, H1 isomer), 4.35 (dd, J = 12.8, 5.4 Hz, 1 H,

OCH₂CH=N-O E isomer), 4.23 (dd, J = 12.8, 6.4 Hz, 1 H, OCH₂CH=N-O E

isomer), 3.94 (dd, J = 10.7, 8.4 Hz, 1 H, H2 Z isomer), 3.93 (dd, J = 10.7,

8.4 Hz, 1 H, H2 E isomer), 3.85 (d, J = 3.4, 2 H, H2 Z and E isomer), 3.79

(dd, J = 11.4, 6.8 Hz, 2 H, H6 Z and E isomer), 3.75 (dd, J = 11.3, 5.3 Hz,

2 H, H6 Z and E isomer), 3.60 (dd, J = 10.6, 3.3 Hz, 2 H, H3 Z and E iso-

mer), 3.50 (ddd, J = 7.8, 6.6, 5.3 Hz, 2 H, H5 Z and E isomer), 2.00 (s,

3 H, NHCOCH₃Z isomer), 1.98 (s, 3 H, NHCOCH₃E isomer).

¹³C NMR (CD₃OD, 125 MHz): δ = 174.6 (C=O), 152.2 (OCH₂-CH=N-O Z

isomer), 149.4 (OCH₂-CH=N-O E isomer), 139.4 (C_Ar), 129.7 (C_Ar),

129.6 (C_Ar), 129.5 (C_Ar), 129.3 (C_Ar), 129.3 (C_Ar), 103.5 (C1 Z isomer),

102.9 (C1 E isomer), 77.7 (CH_2BnZ isomer), 77.3 (C5 Z isomer), 77.3

(C5 E isomer), 77.2 (CH_2BnE isomer), 73.7 (C3 Z and E isomer), 70.0

(C4 Z and E isomer), 67.1 (OCH₂CH=N-O E isomer), 65.0 (OCH₂CH=N-

O Z isomer), 62.9 (C2 Z and E isomer), 54.6 (C2 E isomer), 54.5 (C2 Z

isomer), 23.4 (NHCOCH₃).

Z isomer), 4.50 (dd, J = 16.5, 3.8 Hz, 1 H,

¹H NMR (CD₃OD, 500 MHz): δ = 7.57 (dd, J = 6.2, 5.4 Hz, 1 H,

OCH₂CH=N-O E isomer), 7.40–7.26 (m, 10 H, 5 H_ArE isomer + 5 H_Ar

Z

isomer), 6.98 (t, J = 3.6 Hz, 1 H, OCH₂CH=N-O Z isomer), 5.10 (s, 2 H,

CH_2BnZ isomer), 5.07 (s, 2 H, CH_2BnE isomer), 4.60 (dd, J = 16.6, 3.6 Hz,

1 H, OCH₂CH=N-O

Z isomer), 4.51 (dd, J = 16.6, 3.7 Hz, 1 H,

OCH₂CH=N-O Z isomer), 4.34 (dd, J = 12.9, 5.4 Hz, 1 H, OCH₂CH=N-O E

isomer), 4.25 (dd, J = 12.9, 6.2 Hz, 1 H, OCH₂CH=N-O E isomer), 4.22

(d, J = 7.3 Hz, 1 H, H1 Z isomer), 4.20 (d, J = 7.3 Hz, 1 H, H1 E isomer),

3.68–3.54 (m, 4 H, H4 + H5 E and Z isomer), 3.53–3.42 (m, 4 H, H2 +

H3 E and Z isomer), 1.28 (d, J = 5.6 Hz, 3 H, H6 E isomer or H6 Z iso-

mer), 1.26 (d, J = 5.6 Hz, 3 H, H6 E isomer or H6 Z isomer).

¹³C NMR (CD₃OD, 125 MHz): δ = 152.5 (OCH₂-CH=N-O Z isomer),

149.6 (OCH₂-CH=N-O E isomer), 139.6 (C_Ar), 139.5 (C_Ar), 129.7 (C_Ar),

129.6 (C_Ar), 129.5 (C_Ar), 129.3 (C_Ar), 129.2 (C_Ar), 105.4 (C1 Z isomer),

104.7 (C1 E isomer), 77.7 (CH_2BnZ isomer), 77.3 (CH_2BnE isomer), 75.5

(C3 or C2 E and Z isomer), 73.4 (C5 E and Z isomer), 72.5 (C4 E or Z

isomer), 72.5 (C4 E or Z isomer), 72.4 (C3 or C2 E and Z isomer), 67.4

(OCH₂CH=N-O E isomer), 65.2 (OCH₂CH=N-O Z isomer), 17.1 (C6 E

and Z isomer).

HRMS (ESI): m/z [M + Na]⁺calcd for C₁₇H₂₄N₂NaO₇: 391.1481; found:

391.1477.

N

J. J. Reina et al.

Paper

Synthesis

(E/Z)-O-β-D-Galactopyranosyl-(1-4)-β-D-glucopyranosyl Acetalde-

hyde O-Benzyl Oxime (56)

isomer), 76.1 (CH_2BnE isomer), 73.7, 63.1, 71.8, 71.8, 71.0, 71.0, 70.8,

70.5, 70.3, 70.3, 69.9, 69.8, 60.4, 67.1, 65.9, 65.5 (C6), 64.6

(OCH₂CH=N-O E isomer), 61.96, 61.35 (OCH₂CH=N-O Z isomer).

HRMS (ESI): m/z [M + Na]⁺calcd for C₂₇H₄₁NNaO₁₇: 674.2272; found:

According to Procedure C, compound 56 (10.8 mg, 85%) was obtained

as a colorless solid after HPLC purification (t_R9.2 min).

¹H NMR (D₂O-CD₃OD, 500 MHz):

δ = 7.53 (t, J = 5.5 Hz, 1 H,

674.2265.

OCH₂CH=N-O E isomer), 7.42–7.22 (m, 10 H, H_Ar), 6.96 (t, J = 3.8 Hz,

1 H, OCH₂CH=N-O Z isomer), 5.01 (s, 3 H, CH_2BnZ isomer), 5.00 (s, 3 H,

CH_2BnE isomer), 4.55 (dd, J = 16.6, 3.8 Hz, 1 H, OCH₂CHN Z isomer),

4.49 (dd, J = 16.6, 3.8 Hz, 1 H, OCH₂CHN Z isomer), 4.39–4.20 (m, 6 H,

OCH₂CHN Z isomer + H1A + H1B Z and E isomer), 3.79 (d, J = 3.4 Hz,

2 H, H4B Z and E isomer), 3.79–3.27 (m, 20 H, H3A + H4A + H5A +

2 H6A + H2B + H3B + H5B + 2 H6B Z and E isomer).

¹³C NMR (D₂O-CD₃OD, 125 MHz): δ = 151.6 (OCH₂-CH=N-O Z isomer),

149.4 (OCH₂-CH=N-O E isomer), 137.4 (C_Ar), 137.2 (C_Ar), 128.9 (C_Ar),

128.6 (C_Ar), 128.4 (C_Ar), 103.4 (C1), 102.9 (C1), 78.7, 76.3, 76.0, 75.8,

75.2, 74.8, 73.1, 71.4, 69.0, 66.1, 61.4 (C6), 60.3 (C6).

Funding Information

This work was partially supported by the Spanish Agencia Estatal de

Investigación (AEI) [CTQ2014–59646-R], the Xunta de Galicia

(ED431G/09, ED431C 2017/25 and 2016-AD031) and the ERDF. J.M.

received a Ramón y Cajal (RYC-2013–13784), an ERC-Stg (DYNAP-

677786) and a Young Investigator Grant from the Human Frontier Sci-

ence Research Program (RGY0066/2017).

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HRMS (ESI): m/z [M + Na]⁺calcd for C₂₁H₃₁NNaO₁₂: 512.1744; found:

512.1738.

Acknowledgment

We thank Xosé González Parga (Dpto. de Química Orgánica, Facultad

de Farmacia, USC) for his assistance with ozonolysis reactions.

(E/Z)-O-α-D-Glucopyranosyl-(1-4)-β-D-glucopyranosyl Acetalde-

hyde O-Benzyl Oxime (57)

According to Procedure C, compound 57 (10.2 mg, 80%) was obtained

as a colorless solid after HPLC purification (t_R9.2 min).

Supporting Information

¹H NMR (D₂O-CD₃OD, 500 MHz):

δ = 7.53 (t, J = 5.6 Hz, 1 H,

Supporting information for this article is available online at

OCH₂CH=N-O E isomer), 7.42–7.26 (m, 10 H, H_Ar), 6.97 (t, J = 4.0 Hz,

1 H, OCH₂CH=N-O Z isomer), 5.28–5.18 (m, 2 H, H_1BZ and E isomer),

5.03 (s, 3 H, CH_2BnE isomer), 5.02 (s, 3 H, CH_2BnZ isomer), 4.54 (td,

J = 4.5, 1.9 Hz, 1 H, OCH₂CHN Z isomer), 4.34–4.17 (m, 3 H, OCH₂CHN

Z isomer + H1A Z and E isomer), 3.81–3.43 (m, 18 H, H3A + H4A +

2 H6A + H2B + H3B + H4B + 2 H6B Z and E isomer), 3.37–3.26 (m, 2 H,

https://doi.org/10.1055/s-0036-1591082.

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References

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(8) Baskin, J. M.; Prescher, J. A.; Laughlin, S. T.; Agard, N. J.; Chang, P.

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H

_5A), 3.24–3.13 (m, 4 H, H2A + H5B Z and E isomer).

¹³C NMR (D₂O-CD₃OD, 125 MHz): δ = 152.0 (OCH₂-CH=N-O Z isomer),

149.7 (OCH₂-CH=N-O E isomer), 137.3 (C_Ar), 129.1 (C_Ar), 129.0 (C_Ar),

128.8 (C_Ar), 128.8 (C_Ar), 128.7 (C_Ar), 128.6 (C_Ar), 101.6 (C1A), 100.4

(C1B), 77.7, 77.5, 76.4, 76.0, 74.9, 73.4, 73.2, 73.0, 72.2, 69.7, 66.0,

64.0, 60.9 (C6), 60.8 (C6).

HRMS (ESI): m/z [M + Na]⁺calcd for C₂₁H₃₁NNaO₁₂: 512.1744; found:

512.1740.

O-α-D-Mannopyranosyl-(1-3)-O-[α-D-mannopyranosyl-(1-6)]-α-

D-mannopyranosyl Acetaldehyde O-Benzyl Oxime (58)

According to Procedure C, compound 58 (10.0 mg, 85%) was obtained

after HPLC purification (t_R9.0 min).

¹H NMR (D₂O, 500 MHz): δ = 7.63 (t, J = 4.0 Hz, 1 H, OCH₂CH=N-O E

isomer), 7.49 (m, 10 H, H_Ar), 7.02 (t, J = 4.0 Hz, 1 H, OCH₂CH=N-O Z

isomer), 5.11 (s, 2 H, CH_2BnE isomer), 5.10 (s, 2 H, CH_2BnZ isomer),

5.05 (s, 2 H, H1B Z and E isomer), 4.83 (s, 1 H, H1A Z isomer), 4.82 (s,

1 H, H1A E isomer), 4.80 (s, 2 H, H1C Z and E isomer), 4.49 (ddd,

J = 16.0, 4.1, 1.3 Hz, 1 H, OCH₂CHN Z isomer), 4.40 (ddd, J = 16.0, 4.0,

1.3 Hz, 1 H, OCH₂CHN- E isomer), 4.27–4.16 (m, 2 H, OCH₂CHN E iso-

mer), 4.07 (d, J = 8.3 Hz, 1 H, H2C), 4.04–3.99 (m, 1 H, H2B), 3.95–3.88

(m, 4 H, H2A + H2B Z and E isomer), 3.87–3–81 (m, 13 H, H3B + H6 Z

and E isomer), 3.81–3.76 (m, 3 H), 3.75–3.68 (m, 10 H), 3.66–3.54 (m,

10 H).

(9) Ning, X.; Temming, R. P.; Dommerholt, J.; Guo, J.; Blanco-Ania,

D.; Debets, M. F.; Wolfert, M. A.; Boons, G.-J.; Van Delft, F. L.

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Bertozzi, C. R. J. Biol. Chem. 1998, 273, 31168.

¹³C NMR (D₂O, 125 MHz): δ = 152.2 (OCH₂-CH=N-O Z isomer), 149.9

(OCH₂-CH=N-O E isomer), 129.2 (C_Ar), 128.9 (C_Ar), 128.8 (C_Ar), 128.6

(C_Ar), 102.8 (C1B), 100.7 (C1), 100.6 (C1), 99.9 (C1), 78.8, 76.3 (CH_2BnZ

O

J. J. Reina et al.

Paper

Synthesis

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Article Doi

Glycosyl Aldehydes: New Scaffolds for the Synthesis of Neoglycoconjugates via Bioorthogonal Oxime Bond Formation

DOI: 10.1055/s-0036-1591082

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Full text of DOI:10.1055/s-0036-1591082

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