Iron(iii) chloride modulated selective 1,2-trans glycosylation based on glycosyl trichloroacetimidate donors and its application in orthogonal glycosylation

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Iron(III) chloride modulated selective 1,2-trans

glycosylation based on glycosyl

Cite this: RSC Adv., 2016, 6, 105589

trichloroacetimidate donors and its application in

orthogonal glycosylation†

*

Mana Mohan Mukherjee, Nabamita Basu‡ and Rina Ghosh

The development of a new glycosylation method for eﬃcient stereoselective synthesis of b-gluco- and

galactosides from their corresponding armed trichloroacetimidate donors mediated by 10 mole% of

FeCl₃has been focused. FeCl₃has also been applied to a number of glucose, galactose, mannose and

rhamnose based trichloroacetimidate donors with various protecting groups incorporated at the C-2-

position to prepare a variety of disaccharides and trisaccharides with excellent 1,2-trans selectivity. FeCl₃

can also modulate the 1,2-trans selectivity of the reaction of 2-O-alkylated gluco- and galacto-pyranosyl

trichloroacetimidates with phenolic compounds leading to the generation of the corresponding b-O-aryl

glycosides in excellent yield and selectivity. Apart from these the present methodology has been

successfully utilized for double glycosylation and orthogonal glycosylation reactions along with its

application in one-pot three component orthogonal glycosylation reactions for synthesis of a trisaccharide.

Received 31st August 2016

Accepted 26th October 2016

DOI: 10.1039/c6ra21859h

www.rsc.org/advances

Stereocontrol in the absence of usual neighbouring O-acyl

group participation is considerably more challenging. Many

Introduction

factors, such as steric hindrance of protecting groups, reaction

solvent, and temperature can aﬀect the stereochemical outcome

of a glycosylation reaction, and these eﬀects are typically diﬃ-

cult to predict for any given donor–acceptor pair. So, better

methods to control stereoselectivity in the absence of neigh-

bouring ester group participation are also needed.

Beyond their traditionally accepted roles as energy sources and

structural polymers, oligosaccharides and glycoconjugates

serve critical roles in a wide range of biological processes like

viral and bacterial infection, angiogenesis and tumour cell

metastasis, toxin interaction, inammation and immune

response, cell growth and proliferation, and many other cell–

cell communications.¹However, such carbohydrates are diﬃ-

cult to isolate from natural sources with acceptable purity and

in satisfactory quantities. The key step in the synthesis of

oligosaccharides is the formation of the glycosidic linkages

between monosaccharide units. The anomeric stereoselectivity

can be controlled by the use of protecting groups that are

capable of neighbouring group participation. For example,

esters at the C-2 position of a glycosyl donor typically provide

high selectivity for the 1,2-trans glycoside product. Occasionally,

however, it suﬀers from several drawbacks too, such as low

reactivity of the ester protected glycosyl donor prolonging

reaction time and lowering of yield,²competitive formation of

1,2-ortho ester³and migration of C-2 ester functionality to other

positions.⁴

On the other hand, b-O-aryl glycosides have been recently

found to exhibit anti tumour, anti HIV and anti bacterial

activities. b-O-Aryl glycoside formation is considered as a diﬃ-

cult task due to electron withdrawing power of the aromatic

ring, the facile rearrangement of the resulting O-aryl glycosides

to their corresponding C-aryl glycosides and steric hindrance

from substituents on phenolic glycosyl acceptors;⁵hence their

stereo-controlled synthesis has become a challenging job.⁶

Glycosyl acetates, halides and trichloroacetimidates (TCA) have

been used as donors in the formation of b-O-aryl glycosides.⁶

Glycosyl acetates usually provide the b-O-aryl glycosides with

lower yields than trichloroacetimidates due to anomerization of

both the glycosyl donor and the coupling product.⁶The b-O-aryl

glycosides can be formed in the glycosylation reaction by

employing ester functionalities as the directing group at the C-2

position of glycosyl donors. In some cases, formation of

orthoester side products and migration of the C-2-O-acyl func-

tionality are also observed in the reaction.^3,7

Department of Chemistry, Jadavpur University, Jadavpur, Kolkata 700032, West

Bengal, India. E-mail: ghoshrina@yahoo.com

† Electronic supplementary information (ESI) available. CCDC 1501233. For ESI

and crystallographic data in CIF or other electronic format see DOI:

10.1039/c6ra21859h

Since the rst paper on Schmidt's glycosylation method was

published in 1980,^8a,btill date trichloroacetimidates have been

among the most widely used glycosyl donors.^8cTheir popularity

‡ At present: Department of Organic Chemistry, IACS, Jadavpur, Kolkata 700032,

India.

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comes from their relative ease of synthesis by base-catalyzed glycosylation protocol using FeCl₃as a green catalyst. Unlike all

addition of trichloroacetonitrile to the anomeric hydroxy other reported glycosylation methods (except the reports made

group⁹and their easy activation; it also opens up the scope for by Nguyen et al.¹⁹and by Schmidt et al.²¹) based on armed tri-

orthogonal glycosylation. The glycosyl trichloroacetimidate chloroacetimidate glycosyl donors the present one generated

donors are generally activated by strong Lewis acids such as the corresponding glycosides in excellent yields and 1,2-trans

BF₃$OEt₂,^8aTMSOTf,^9aTf₂O,¹⁰ZnBr₂,¹¹NOBF₄,¹²Sm(OTf)₃,^13aselectivity (Scheme 1). The acceptable catalyst load and low cost

LiClO₄,¹⁴LiOTf,¹⁵or other systems like I₂/Et₃SiH,^13bacid washed (Scheme 1) of FeCl₃together with its greenness particularly in

13c,d

HClO₄/SiO₂,¹⁶Amberlyst 15,¹⁷AuCl₃– respect of the scope of its future utilization for large scale

˚

4 A molecular sieves,

phenylacetylene,¹⁸etc.; many of these are however not without ramication make this procedure very attractive.

limitations.

In the last decade FeCl₃has drawn much attention of the

researchers worldwide for its wide range of application in

organic synthesis.²³Our strategy for 1,2-trans glycosylation was

to exploit the ability of this rst row transition metal-Lewis acids

to direct glycosylation of trichloroacetimidate donor. The

choice of FeCl₃was based on the presumption that, for glucose

and galactose donors, like Pd a seven member cyclic chelate^19,24

(b) may be the possibility involving electronically vacant metal

center (Fe), a-imidate nitrogen and C-2-oxygen of glycosyl tri-

chloroacetimidate donor (a) which in eﬀect would block the a-

face of the proposed TS (c) for the attacking incoming nucleo-

philic acceptor, so that ultimately it can result in b-glycoside (d),

vide Fig. 1.

Results and discussion

Recently Nguyen et al.¹⁹have reported trichloroacetimidate

(TCA, containing 2-O-alkyl group) activation in high to excellent

1,2-trans selectivity utilizing second row transition metal

complexes involving Pd in low catalyst loading. In another

report chiral Brønsted acid has been utilized for such purpose.²⁰

In a more recent report by Schmidt et al. it has been

demonstrated that b-glycosylation based on armed tri-

chloroacetimidate donors using Au(^III) or Au(I) chloride catalyst

via formation of catalyst-glycosyl acceptor adduct permits

glycosyl donor activation with concomitant glycosyl acceptor

anion transfer to the anomeric carbon.²¹But the reported

catalysts are very much expensive, and sometimes toxic for the

living body as well as environment. In continuation of our

research work on glycoscience,²²we report herein a 1,2-trans

Our initial study was performed with 2,3,4,6-tetra-O-benzyl-^D-

glucopyranosyl trichloroacetimidate, 1 as the armed glycosyl

donor and methyl 2,3,4-tri-O-benzoyl-a-^D-glucopyranoside 2 as

the acceptor. Upon treatment of these coupling partners in

1.2 : 1 molar ratio with 30 mole% FeCl₃at ꢀ5 ^ꢁC to room

temperature for 1 hour, the desired disaccharide 3 was isolated

1

in 67% yield as a single b isomer. H-NMR spectrum showed

one anomeric proton appearing at d 4.55 ppm with J 8.0 Hz

corresponding to the H⁰₁indicating 1,2-trans glycosylation. This

was also corroborated by the appearance of peaks at d 101.9 and

104.0 ppm, corresponding to the anomeric carbons C⁰₁and C₁,

respectively. Higher d value of the reducing anomeric carbon, in

spite of it having an a-stereochemistry is attributed to the

deshielding caused by three benzoyl protections on this

pyranoside ring. The result, as we presumed, was indeed

interesting and encouraging too, as this was clearly implying

the ability of FeCl₃to activate trichloroacetimidate stereo-

selectively in the presence of apparently silent spectator pro-

tecting group like O-benzyl or without assistance by the solvent.

As an initial eﬀort for optimization of a standard procedure

for glycosylation we applied diﬀerent catalyst loading (of FeCl₃)

Scheme 1 Comparison of the recent works with the present one

(inset).

Fig. 1 Anticipated transition states for FeCl₃catalyzed glucose and galactose based armed donors.

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with variation in temperature and solvent, as well as few other apply this method for preparative purpose also. When 4,6-O-

catalysts too (Table 1). Finally we selected the most economi- benzylidene-2,3-di-O-benzyl-a-^D-glucopyranosyl tri-

cally acceptable and eﬃcient reaction condition as 10 mole% chloroacetimidate donor, 10 reacted with acceptor 8 the desired

ꢁ

FeCl₃at ꢀ60 C to room temperature and used the process for disaccharide 11 was obtained in 87% yield as b isomer; the

further studies.

reaction of it's galactose analogue 21 with acceptor 22 gave the

With an optimized reaction condition in hand we then set b-disaccharide 23 in 92% yield (entries 5 and 11, respectively,

out to explore the scope of FeCl₃catalyzed 1,2-trans selective Table 2). When armed ^D-mannopyranosyl trichloroacetimidate

glycosylations. A variety of nucleophilic glycosyl acceptors donor 19 was allowed to react with nucleophilic acceptor 4, the

incorporating various protecting groups like ether, iso- corresponding a-disaccharide 20 was obtained in high yield

propylidene ketals and benzylidene acetals were exemplied (entry 10, Table 2).

with glycosyl donor 1 (Table 2). Glycosyl acceptors with least

The other glycosyl trichloroacetimidate donor systems that

reactive 4-OH, hindered tertiary alcohol like 1-adamentanol and needed to be exercised in FeCl₃catalyzed glycosylation protocol

sensitive diisopropylidene protection (4, 6 and 8, respectively) in were those with C-2-O-acyl protecting donors. It is expected that

reaction with 1 generated the corresponding disaccharides 5, 7 ester functionality from C-2 position might control the forma-

and 9 in excellent yields (entries 2, 3 and 4, Table 2), with tion of 1,2-trans through the usual neighbouring group partic-

notable b selectivity compared to the reported ones.^13a,19b,cThe ipation. Glycosylation of donors 24, 27, 29, 32, 34, and 36 with

structure of compound 7 (CCDC no. 1501233) was conrmed by a variety of glycosyl acceptors like 25, 30 and 2 separately

its X-ray structure (Fig. 2).

(entries 1 to 6, Table 3) provided the corresponding 1,2-trans

The eﬃcacy of the present procedure was further established selective products 26, 28, 31, 33, 35 and 37.

when we examined this chemistry with 2,3,4,6-tetra-O-benzyl-a-

To further demonstrate the eﬃcacy of the glycosylation

D-galactopyranosyl trichloroacetimidate 12; the armed donor is protocol, we set out to pursue a glycosylation reaction of donor 1

well known for its a-directive eﬀect for 4 axial –OH group. with a disaccharide acceptor 38, where we get the trisaccharide,

Compared to other reported methods,^25,26we observed 39 in 89% yield and as b anomer. It is to be noted here that the

remarkable b selectivity when glycosylation reactions of 12 were reported method using Pd(PhCN)₂Cl₂+ AgOTf produces the

performed with carbohydrate acceptors 2, 4, 15 and 17 having trisaccharide 39 in 71% yield with b : a ¼ 12 : 1 anomeric

nucleophilic hydroxy group on C-6, C-4, C-3 and C-2 positions, ratio.^19cThen we turned to a couple of double glycosylation of

respectively; irrespective of their position and reactivity, the carbohydrate diol. Pair up of 4,6-glucopyranosyl diol 41 and

corresponding desired disaccharides (13, 14, 16 and 18) were phthalimide protected glucosamine donor 40, resulted with the

obtained in excellent yield and b selectivity (entries 6 to 9, desired trisaccharide 42 in 83% yield where as the same diol

Table 2).

acceptor 41 reacted with the rhamnosyl donor 27 aﬀording 81%

The present method also responded eﬃciently under a scale- of the desired trisaccharide 43 (Scheme 2).

up (ꢂ30 fold) condition when applied for preparation of 3 from

Next, we turned our attention to apply the present protocol

reaction of 1 and 2 (entry 1, Table 2), thus opening up scope to for the synthesis of b-aryl glycosides. FeCl₃catalyzed b-selective

Table 1 Standardization of optimum reaction condition^a

Entry

Catalyst (mole%)

Reaction temperature

Time

Yield^b

(a/b ratio)^c

1

2

3

4

5

6

7

8

FeCl₃(30)

FeCl₃(20)

FeCl₃(30)

FeCl₃(20)

FeCl₃(10)

FeCl₃(5)

FeCl₃(10)

FeBr₃(30)

In(OTf)₃(30)

ꢀ5 ^ꢁC to rt

ꢀ30 ^ꢁC to rt

ꢀ60 ^ꢁC to rt

ꢀ80 ^ꢁC to rt

ꢀ60 ^ꢁC to rt

ꢀ50 ^ꢁC to rt

1 h

67%

72%

83%

90%

96%

92%

94%

93%

94%

93%

59%

62%

(b only)

(b only)^d

(2 : 3)^e

45 min

35 min

45 min

9

10

11

12

13

(b only)^f

(b only)^g

(1 : 9)

(b only)

a

All reactions were carried out in DCM with 1.2 equiv. of donor. ^bIsolated yield. ^{c 1}H NMR ratio. ^dUsing MeCN : DCM (1 : 2). ^eUsing Et₂O : DCM

(1 : 1). Using 99.99% FeCl₃of Sigma Aldrich. ^gUsing b anomer of 1 as donor.

f

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Table 2 Glycosylation with C-2 alkyl donors^a

Yield^b

Entry Donor

Acceptor Product

(a : b)

Entry Donor

Acceptor

Product

(a : b)

96%

1

6

2

95% b

b (89%)^c

2

3

1

93% b

94% b

7

8

9

12

4

88% b

89% b

90% b

4

1

85% b

87% b

10

11

4

87% a^d

5

8

92% b

a

All reactions were carried out in dry DCM with 1.2 equiv. of donor at ꢀ60 ^ꢁC to rt. ^bIsolated yield. ^cUse of glycosyl donor in 1.5 g scale. ^dReaction

was carried out at ꢀ5 ^ꢁC to rt.

glycosides 45, 47 and 51 were isolated in excellent yield and b-

selectivity (entries 1, 2 and 4, Table 4). Similarly, tetra-O-benzyl-

D-galactopyranosyl trichloroacetimidate substrate 12 was also

examined under the standardized condition to react with

diﬀerent phenols 44, 53, and 55; in each case we found the

corresponding desired b-O-aryl galactoside 52, 54 and 56 to be

formed with promising result on the ground of yield and

selectivity (entries 5 to 7, Table 4).

To explore further the applicability of this procedure we then

chose a sterically hindered 2,6-dimethylphenol 48. Gratifyingly,

this phenol acceptor 48 was able to couple with both donors 1

and 12 to provide the corresponding O-aryl glycosides 49 and

57, respectively with excellent yield and anomeric selectivity

(entries 3 and 8, Table 4). It may be mentioned here that the

reported coupling between phenol 48 and tetra-O-benzyl-^D-glu-

cothioglycoside donor aﬀords the desired product 49 with

excellent yield (90%) albeit with low selectivity (a : b ¼

2.6 : 1),^27awhereas the sulfoxide approach gave 70% yield as

a 2 : 1 mixture of a- and b-anomer.^27b

Fig. 2 ORTEP diagram of compound 7.

Aer achieving a convenient synthetic route for 1,2-trans

selective glycosylation with trichloroacetemidate donors, we

also sought to verify the eﬃciency of the Lewis acidity of FeCl₃to

promote thioglycoside activation in combination with NIS. For

arylation was found eﬀective for D-glucopyranosyl tri-

chloroacetimidate donor 1 with a variety of electron-rich

phenols (44, 46 and 50), and the corresponding desired

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Table 3 Glycosylation with C-2 ester protected sugar^a

Entry

Donor

Acceptor

Product

Yield^b(a : b)

90% a only

1

2

3

25

89% a only

91% b only

4

5

30

2

91% b only

88% b only

6

2

90% b only

a

b

All reactions were performed in dry DCM with 1.2 equiv. of donor and 10 mole% of FeCl₃at ꢀ60 ^ꢁC to rt. Isolated yield.

Table 4 Glycosylation with diﬀerent phenol^a

Entry

1

Donor

Acceptor

Product

Yield^b(a : b)

97% b

1

2

3

1

97% b

90% b

4

5

1

92% b

97% b

12

44

Scheme

2 Glycosylation with disaccharide acceptor and double

glycosylations.

6

7

12

95% b

94% b

this purpose thioglycoside donors 58, 61, 63 and 66 were

allowed to couple with benzyl N-(3-hydroxypropyl) carbamate 59

(entries 1 and 2, Table 5), 1-adamentanol 6 (entries 3 and 4,

Table 5) and carbohydrate acceptor like 4 (entry 5, Table 5) to

produce the corresponding glycosides 60, 62, 64, 65 and 67 in

excellent respective yield and expected b-steroselectivity due to

C-2 neighbouring group participation. A rare sugar derivative of

D-rhamnose donor 68 was allowed to couple with similar

acceptor 69 to give stereoselectively the desired disaccharide 70

8

12

48

91% b

a

All reactions were performed in dry DCM with 1.2 equiv. of donor and

b

10 mole% of FeCl₃at ꢀ5 ^ꢁC to rt. Isolated yield.

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Table 5 Glycosylatin reaction based on thioglycosides^a

Entry

Donor

Acceptor

Product

Yield^b(a : b)

88% b only

92% b only

1

2

59

6

3

94% b only

4

5

6

58

6

4

89% b only

91% b only

91% a only

7

90% a only

a

b

All reactions were performed in dry DCM with 1.2 equiv. of donor 1 equiv. NIS and 20 mole% of FeCl₃at ꢀ5 ^ꢁC to rt. Isolated yield.

in 91% yield (entry 6, Table 5). Reaction of mannosyl donor 71 of the thermodynamic product, a-glycoside (85). All the reac-

with di-mannoside acceptor 72 produces the mannose trisac- tions under Tables 1–6 clearly represent the applicability of

charide 73 in 90% yield (entry 7, Table 5). These reactions thus FeCl₃in stereoselective glycosylation via trichloroacetemidate

prove the ability of FeCl₃to catalyse thioglycoside activation too, activation, thioglycoside activation in combination with NIS

in combination with NIS and opens up the gateway for its and also orthogonal glycosylation of the former in the presence

further elaboration in orthogonal glycosylations.

of the thioglycoside acceptor.

Orthogonal glycosylation of trichloroacetimidate donors

Now, nally the eﬃcacy of FeCl₃was exemplied for chain

with thioglycosides pave the way for eﬃcient streamline oligo- elongation, essential for oligosaccharide synthesis²⁹by one pot

saccharide assemblies.²⁸Activity of FeCl₃towards orthogonal sequential glycosylation with trichloroacetimidate donor fol-

glycosylation of trichloroacetimidate donors with thio glycoside lowed by thioglycoside activation (Scheme 3).

acceptors have also been investigated there aer (Table 6).

For this trichloroacetimidate donor 1 was allowed to react

Glycosylation with orthogonal trichloroacetimidate donor 1 and with 4-methylphenyl 2,3,4-tri-O-benzoyl-1-thio-b-^D-glucopyr-

the glycosyl acceptor 74 bearing thiophenyl group at its anoside 86 at ꢀ60 ^ꢁC to room temperature in the presence of 10

anomeric position produced the corresponding b disaccharide mole% FeCl₃; aer consumption of both of the starting mate-

75 in 85% yield (entry 1, Table 6). Similar reaction between 2,3- rials (checked by TLC) and aer an increase of the reaction

di-O-benzyl-4,6-O-benzylidene-a-^D-glucopyranosyl

tri- temperature to 0 ^ꢁC the acceptor 8 was injected followed by

chloroacetimidate donor 10 and phenyl 2,3,6-tri-O-benzyl-1- addition of NIS along with additional 10 mole% FeCl₃. The

thio-b-^D-glucopyranoside 74 generated the desired b disaccha- reaction was complete within 15 minutes giving the trisaccha-

ride 76 in 94% yield (entry 2, Table 6). Coupling of tri- ride 39 in 87% yield as b anomer (Scheme 3).

chloroacetimidate donors 77, 80 and 83 separately with the

So far we have observed that glucose and galactose based

thioglycoside acceptors 78 (entry 3, Table 6), 81 (entry 4, Table 6) trichloroacetimidate armed donors are activated by FeCl₃

and 84 (entry 5, Table 6), respectively produced the corre- generating selectively 1,2-trans glycosides in reaction with

sponding glycosides 79, 82 and 85 in 94%, 92% and 88% yield. a variety of glycosyl acceptors (Tables 2, 4 and 6). It is also

Unexpectedly, the armed fucosyl TCA donor 83 produced interesting to note that the reaction of b-TCA donor with 2

selectively the corresponding a-glycoside, 85. This could be due under similar condition also produced the same product 3 in

to much high reactivity of 83, for which here the glycosylation comparable yield and selectivity (entry 11, Table 1). Moreover, in

reaction probably proceeds via formation of the corresponding situ anomerisation of each of a- or b-TCA in the presence of

oxonium ion intermediate rather than via the corresponding Fe- FeCl₃in CH₂Cl₂solution could not also be established. These

chelated TS. This might cause the anomeric selectivity in favour facts preclude the possibility of these reactions to proceed

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Table 6 Orthogonal glycosylations^a

Entry

Donor

Acceptor

Product

Yield^b(a : b)

85% b

1

2

1

10

74

94% b

3

4

94% a

92% a

5

88% a

a

b

All reactions were performed in dry DCM with 1.2 equiv. of donor and 10 mole% of FeCl₃at ꢀ60 ^ꢁC to rt. Isolated yield.

a 7-membered chelate in each case of the a- and b-TCA donor.

Whereas the former chelate is attacked from the b-side of the

carbocation intermediate by the incoming glycosyl acceptor (a-

side being blocked, Fig. 1), but, for the more reactive b-TCA

probably there is suﬃcient time lag between breaking of the b-

C₁–O bond of the donor and formation of the b-glycosidic bond

so that the approach of the incoming nucleophile can be

accommodated at the b-side, since the a-side is still blocked by

the bulky pendant C₂–O–[Fe]NCOCCl₃group. In the case of

mannosyl donor (entry 10, Table 2) possibility of chelation of

catalyst with C-1 and C-2 substituents in the reactant donor

does not arise due to their 1,2-trans diaxial orientation. So here

probably the reaction proceeds via usual intermediate oxo-

carbenium ion.³⁰It has already been reported that with greater

number of degrees of freedom, a direct steric interaction

between the 6-benzyloxy group and the aglycon is possible, and

this interaction will predominate the formation of a-anomer

over the b one.³¹Moreover, the bulk of benzyloxy group at 4-

Scheme 3 Application in one-pot sequential glycosylation reaction.

following S_N2 like pathway. All these thus support our initial

proposition of the reaction proceeding via a S_N1 type mecha-

nistic pathway through probably an initial formation of

Table 7 Glycosylation reactions in support of anticipated mechanistic pathway

Entry

Donor

Acceptor

Product

Yield^aa : b ratio

1

2

93% 0 : 1

2

87% 1 : 0

a

Isolated yield.

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position also restricts the conformational space allotted for 3-O- gel 60 sorbent (40–63 mm, 230–400 mesh). Thin-layer chroma-

benzyl ether, which in turn might impinge on the conformation tography (analytical and preparative) was performed using

of 2-O-benzyl ether destabilizing the b anomer over the a one.³¹Merck silica gel plates (60-F254) to monitor the reactions and

To corroborate with the above we further planned to perform visualized under UV (254 nm) and/or by charring with 5%

FeCl₃mediated glycosylation reactions (Table 7) using two other ethanolic solution of sulfuric acid. ¹H and ¹³C NMR spectra

armed donors. Like the armed trichloroacetimidate donor 1 were recorded on a Bruker DPX-300 (300 MHz), a Bruker DPX-

bearing C-2–OBn (Table 1), the rst trichloroacetimidate donor 400 (400 MHz), a Bruker DPX-500 (500 MHz), or a Bruker

having a C-2–OMe group 87 (entry 1, Table 7) in reaction with DPX-600 (600 MHz) spectrometer at ambient temperature in

the glycosyl acceptor 2, generated the corresponding disaccha- CDCl₃, and assigned using 2D-methods (COSY, HSQC). Optical

ride 88 (entry 1, Table 7) with exclusive 1,2-trans or b-anomeric rotations were measured using Jasco P-1020 digital polarimeter.

selectivity. This observation precludes the take part of the High Resolution Mass Spectra (HRMS) were measured in

phenyl ring of the 2-O-benzyl protection during formation of the a QTOF I (quadrupole-hexapole-TOF) mass spectrometer with

proposed TS (b or c, Fig. 1). Additional indirect endorsement in an orthogonal Z-spray-electrospray interface on micro (YA-263)

favour of the projected mechanistic pathway (Fig. 1) came from mass spectrometer (Manchester, UK). All the known

a glycosylation reaction of acceptor 15 utilising 2-deoxy glycosyl compounds were characterised by NMR spectroscopic analysis

donor 89 (entry 2, Table 7) which aﬀorded the corresponding and comparing those with their previously reported literature

glycoside 90 in 87% yield but with a-anomeric selectivity, as values.

evidenced by NMR³²(¹H- and ¹³C-) spectra. In the absence of 2-

oxygen formation of TS (b) or (c) (Fig. 1) does not arise here. Materials

With the deoxy donor the reaction probably proceeds via

formation of the usual oxonium ion intermediate.

All glycosydic donors 1, 10, 12, 19, 21, 24, 27, 29, 32, 34, 36, 40,

58, 61, 63, 66, 68, 71, 77, 80, 83, 87, 89 and 91 acceptors 2, 4, 8,

15, 17, 22, 25, 30, 38, 41, 69, 72, 74, 78, 81, 84 and 86 were

Conclusion

prepared according to standard literate procedures. Ada-

mentanol (6), long chain alcohol (59) and arometic nucleophilic

phenols 44, 46, 50, 53 and 55 were purchased at the highest

possible purity from Alfa Aesar and Sigma-Aldrich and used as

received.

In summary, we have demonstrated an eﬃcient general glyco-

sylation reaction condition catalyzed by FeCl₃based on armed

and disarmed trichloroacetimidate donors for the synthesis of

1,2-trans glycosides, and its use as a promoter in combination

with NIS in thioglycoside activation. Advantages of this protocol

include operational simplicity, general excellent yield, use of

a catalytic amount of commercially available inexpensive, green

catalyst for the activation of trichloroacetimidate, and forma-

tion of 1,2-trans glycoside in preparative scale (g) also. The

applicability of this method to a broader scope of phenol

nucleophiles as well as a wide variety of sugar nucleophiles and

its excellent 1,2-trans selectivity both in the presence or absence

of predesigned auxiliary protecting group. Its application in

orthogonal glycosylation using trichloroacetimidate donor with

thioglycoside acceptor, synthesis of a trisaccharide based on

one-pot sequential glycosylation reactions, make this general

protocol a promising one. We believe it will denitely nd

immense application in glyco-chemistry. Ramication of the

present methodology including the orthogonal glycosylation

leading to oligosaccharide synthesis are underway for future

publication.

General procedure for glycosylation with carbohydrate

acceptors

A 10 mL oven-dried round bottom ask was charged with tri-

chloroacetimidate donor (1.2 equiv.), glycosyl acceptor (1

equiv.), and CH₂Cl₂(3 mL). The resulting solution was stirred

˚

on freshly dried 4 A molecular sieves for 40 min at room

temperature under argon atmosphere. Then this mixture was

cooled to ꢀ60 ^ꢁC, FeCl₃(0.1 equiv.) was added, and the reaction

mass was allowed to achieve room temperature. Aer the

acceptor was consumed completely (checked by TLC) molecular

sieves were ltered oﬀ through celite bed. The ltrate was

diluted with CH₂Cl₂and washed subsequently with saturated

NaHCO₃solution and water. The organic layer was dried over

anhydrous Na₂SO₄and concentrated to aﬀord the glycosylated

product. The crude mass was puried by silica gel column

chromatography and collected as pure product.

General procedure for glycosylation with phenol acceptors

Experimental

General procedures

A 10 mL oven-dried round bottom ask was charged with tri-

chloroacetimidate donor (1.2 equiv.), phenol acceptor (1 equiv.),

All reactions were performed in amed-dried asks tted with and CH₂Cl₂(3 mL). The resulting solution was stirred on freshly

˚

rubber septa under a positive pressure of argon, unless other- dried 4 A molecular sieves for 40 min at room temperature

wise stated. Dichloromethane was reuxed with P₂O₅and under argon atmosphere. Then this mixture was cooled to

distilled before use and stored over 4 A molecular sieves. FeCl₃ꢀ5 ^ꢁC, FeCl₃(0.1 equiv.) was added, and the reaction mass was

˚

was purchased from (Merck, India). Traces of water in the donor allowed to achieve room temperature. Aer the acceptor was

and acceptor glycosides were removed by co-evaporation with consumed completely (checked by TLC) molecular sieves were

˚

toluene. Molecular sieves (4 A) were ame dried before use. ltered oﬀ through celite bed. The ltrate was diluted with

Flash column chromatography was performed employing silica CH₂Cl₂and washed subsequently with saturated NaHCO₃

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solution and water. The organic layer was dried over anhydrous 7.5 Hz, ArH). ¹³C NMR (CDCl₃, 125 MHz): d 57.1, 68.7, 68.8, 70.1,

Na₂SO₄and concentrated to aﬀord the glycosylated product. 71.9, 73.1, 73.5, 74.4, 74.7, 74.8, 74.9, 75.6, 76.6, 82.2, 101.9 (C⁰₁),

The crude mass was puried by silica gel column chromatog- 104.0 (C₁), 127.6, 127.7, 127.8, 127.9, 128.2, 128.3, 128.9, 129.4,

raphy (60–120 mesh) and collected as pure product.

129.7, 129.8, 133.2, 133.5, 138.2, 138.6, 165.12 (C]O), 165.5

(C]O), 165.8 (C]O). HRMS (ESI-TOF): calculated for

General procedure for glycosylation with thioglycoside donors

C₆₂H₆₀O₁₄Na (M + Na) 1051.3881 found 1051.3882.

To a mixture of thioglycoside donor (1.1 equiv.) and acceptor (1

equiv.) in dry CH₂Cl₂(5 mL), ame activated molecular sieves

Methyl 2,3,4,6-tetra-O-benzyl-b-^D-glucopyranosyl-(1/4)-2,3,6-

tri-O-benzyl-a-^D-glucopyranoside (5)³³

˚

(4 A) were added. It was stirred at room temperature under

argon atmosphere. Aer 40 min the mixture was cooled to

ꢀ5 ^ꢁC, and NIS (1 equiv.) was added to it. Then FeCl₃(0.2

equiv.) was added. Aer the acceptor was consumed completely

(checked by TLC) reaction mixture was ltered oﬀ through

Celite bed. The ltrate was diluted with CH₂Cl₂and washed

subsequently with saturated sodium thio sulphate, NaHCO₃

solution and water. The organic layer was dried over anhydrous

Na₂SO₄and concentrated to aﬀord the glycosylated product.

The crude mass was puried by silica gel column chromatog-

raphy (60–120 mesh).

The crude residue was puried by silica gel (230–400 mesh)

ash column chromatography (hexane/ethyl acetate, 4 : 1) to

aﬀord the compound 5 in 93% b only as white solid,³³R_f0.33

(80% CH₂Cl₂in hexane); mp 84–85 C (from hexane), lit.³³mp

ꢁ

88–89 ^ꢁC, mp 79–81 ^ꢁC (ether–hexane); [a]²_D⁴+22.8 (c 1.15,

CHCl₃); lit.³³[a]_D²⁴+22 (c 0.4 CHCl₃); ¹H NMR (CDCl₃, 300 MHz):

d 3.34–3.38 (m, 2H), 3.41 (s, 3H, OCH₃), 3.49–3.56 (m, 3H), 3.60–

3.65 (m, 3H), 3.77 (bd, 1H, J ¼ 10.9 Hz, BnH), 3.88–3.94 (m, 2H),

4.02 (t, 1H, J ¼ 9.7 Hz), 4.41–4.48 (m, 4H, BnH), 4.59–4.68 (m,

4H, BnH), 4.77–4.95 (m, 7H, BnH, H₁, H⁰₁), 5.14 (d, 1H, J ¼

11.3 Hz, BnH), 7.23–7.49 (m, 35H, ArH). ¹³C NMR (CDCl₃, 75

MHz): d 55.3, 67.9, 69.1, 70.1, 73.4, 73.7, 74.8, 74.9, 75.2, 75.4,

75.6, 78.1, 78.9, 80.4, 82.8, 84.9, 98.5 (C⁰₁), 102.5 (C₁), 127.1,

127.3, 127.5, 127.6, 127.7, 127.8, 127.82, 128.02, 128.04, 128.08,

128.1, 128.3, 128.4, 128.5, 137.9, 138.3, 138.4, 138.6, 138.62,

138.7, 139.6. HRMS (ESI-TOF): calculated for C₆₃H₇₀O₁₁Na (M +

Na) 1025.4816 and found 1025.4814.

Methyl 2,3,4,6-tetra-O-benzyl-b-^D-glucopyranosyl-(1/6)-2,3,4-

tri-O-benzoyl-a-^D-glucopyranoside (3)³³

A 10 mL oven-dried round bottom ask was charged with

2,3,4,6-tetra-O-benzyl-^D-glucopyranosyl

trichloroacetimidate

donor 1 (48.5 mg, 0.071 mmol, 1.2 equiv.), methyl 2,3,4-tri-O-

benzoyl-a-^D-glucopyranoside 2 (30 mg, 0.06 mmol, 1 equiv.),

and CH₂Cl₂(3 mL). The resulting solution was stirred on freshly

˚

dried 4 A molecular sieves for 40 min at room temperature

under argon atmosphere. Then this mixture was cooled to Adamentyl 2,3,4,6-tetra-O-benzyl-b-^D-glucopyranoside (7)^19c

ꢀ60 ^ꢁC, FeCl₃(1.2 mg, 0.007 mmol, 0.1 equiv.) was added, and

A mixture of 1 (75 mg, 0.11 mmol), 6 (14 mg, 0.088 mmol) and

the reaction mass was allowed to achieve room temperature.

Aer the acceptor was consumed completely (checked by TLC)

molecular sieves were ltered oﬀ through celite bed. The ltrate

was diluted with CH₂Cl₂and washed subsequently with satu-

rated NaHCO₃solution and water. The organic layer was dried

over anhydrous Na₂SO₄and concentrated to aﬀord the glyco-

sylated product. The crude mass was puried by silica gel

column chromatography (60–120 mesh) and collected as

colorless syrup (3, 59.38 mg, 96%).³³

˚

ame activated 4 A molecular sieves were stirred in dry solvent

(4 mL) for 40 min at room temperatu_ꢁre under argon atmo-

sphere. The mixture was cooled to ꢀ5 C, and FeCl₃(1.8 mg,

0.011 mmol) was added to it. Aer the acceptor was consumed

completely (checked by TLC) molecular sieves were ltered oﬀ

through celite bed. The ltrate was diluted with CH₂Cl₂and

washed subsequently with saturated NaHCO₃solution and

water. The organic layer was dried over anhydrous Na₂SO₄and

concentrated to aﬀord the glycosylated product. The crude

residue was puried by silica gel (230–400 mesh) ash column

chromatography (hexane/ethyl acetate, 9 : 1) to aﬀord the

compound 7 (62.3 mg) in 94% b as white solid.^19cR_f¼ 0.72

Scale-up (ꢂ30 fold) experimental procedure for preparation of

3

The scale-up experiment was done following the above reaction (hexane/ethyl acetate, 4/1). Mp 118–120 ^ꢁC (from ethyl acetate,

procedure using 1 (1.47 g, 2.16 mmol), 2 (0.92 g, 1.8 mmol), 4 A pet-ether), [a]²_D⁴+14.2 (c 0.96, CHCl₃); ¹H NMR (CDCl₃, 300

˚

molecular sieves, FeCl₃(35 mg, 0.022 mmol) in dry CH₂Cl₂(45 MHz): d 1.65 (bs, 6H), 1.83–1.93 (m, 6H), 2.17 (bs, 3H), 3.58

mL). Pure chromatographed product (3, 1.65 g) was obtained in (dd, 1H, J ¼ 3.6, 9.7 Hz), 3.60–3.72 (m, 2H), 3.80 (dd, 1H, J ¼

89% yield. R_f¼ 0.18 (hexane/ethyl acetate, 6/1); [a]²_D⁰+3.2 (c 0.8, 3.5, 10.5 Hz), 4.03–4.09 (m, 2H), 4.49 (d, 1H, J ¼ 12.1 Hz, BnH),

CHCl₃); ¹H NMR (CDCl₃, 500 MHz): d 3.31 (s, 3H, OCH₃), 3.33– 4.51 (d, 1H, J ¼ 9.6 Hz, BnH), 4.68 (t, 1H, J ¼ 12.1 Hz, BnH),

3.37 (m, 2H), 3.50–3.58 (m, 4H), 3.81 (dd, 1H, J ¼ 8.5, 11.5 Hz), 4.73 (m, 2H, BnH), 4.83–4.89 (app t, 2H, J ¼ 9.5, 10.5 Hz, BnH),

4.00 (m, 2H), 4.35 (d, 1H, J ¼ 12.0 Hz, BnH), 4.41–4.48 (m, 3H, 5.03 (d, 1H, J ¼ 10.9 Hz, BnH), 5.32 (d, 1H, J ¼ 3.5 Hz, H₁),

BnH), 4.55 (d, 1H, J ¼ 8.0 Hz, H⁰₁), 4.64–4.72 (m, 3H, BnH, H₁), 7.17–7.38 (m, 20H, ArH). ¹³C NMR (CDCl₃, 75 MHz): d 30.7,

4.83 (d, 1H, J ¼ 11.0 Hz, BnH), 4.90 (d, 1H, J ¼ 11.0 Hz, BnH), 36.3, 42.5, 68.8, 69.7, 72.8, 73.4, 74.5, 75.1, 75.5, 78.2, 80.1,

5.32 (t, 1H, J ¼ 9.5 Hz, H₄), 5.39 (app t, 1H, J ¼ 8.5, 9.0 Hz, H₂), 82.1, 89.9 (C₁), 127.5, 127.6, 127.7, 127.76, 127.8, 127.9, 128.0,

5.79 (t, 1H, J ¼ 9.5 Hz, H₃), 7.06 (bd, 2H, J ¼ 5.5 Hz, ArH), 7.16– 128.1, 128.3, 138.36, 138.1, 138.4, 138.42, 139.1. HRMS (ESI-

7.34 (m, 25H, ArH) 7.42 (app t, 2H, J ¼ 7.0, 7.5 Hz, ArH), 7.72 (d, TOF): calculated for C₄₄H₅₀O₆Na (M + Na) 697.3575, found

2H, J ¼ 8.0 Hz, ArH), 7.84 (d, 2H, J ¼ 7.5 Hz, ArH), 7.87 (d, 2H, J ¼ 697.3507.

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Paper

2,3,4,6-Tetra-O-benzyl-b-D-glucopyranosyl-(1/6)-1,2:3,4-di-O-

isopropylidene-a-^D-galactopyranose (9)^19b

Methyl 2,3,4,6-tetra-O-benzyl-b-^D-galactopyranosyl-(1/4)-

2,3,6-tri-O-benzyl-a-^D-glucopyranoside (14)^34,36

The crude residue was puried by silica gel (230–400 mesh) The crude residue was puried by silica gel (230–400 mesh)

ash column chromatography (hexane/ethyl acetate, 9 : 1) to ash column chromatography (hexane/ethyl acetate, 4 : 1) to

aﬀord the compound 9 in 85% b as colorless syrup.^19bR_f¼ 0.36 aﬀord the compound 14 in 88% b as white foam³⁶R_f¼ 0.52

1

(hexane/ethyl acetate, 4/1); [a]²_D²ꢀ24 (c 1.0, CHCl₃); ¹H NMR (hexane/ethyl acetate, 3/1); H NMR (CDCl₃, 300 MHz): d 3.38–

(CDCl₃, 300 MHz): d 1.33 (s, 6H, CH₃), 1.52 (s, 3H, CH₃), 1.55 (s, 3.43 (m, 3H), 3.43 (s, 3H, OCH₃), 3.51–3.68 (m, 4H), 3.77–

3H, CH₃), 3.45–3.50 (m, 2H), 3.59–3.69 (m, 2H), 3.72–3.78 (m, 4.00 (m, 5H), 4.29 (d, 1H, J ¼ 11.8 Hz, BnH), 4.36–4.45 (m, 2H),

2H), 4.11 (m, 1H, H₅), 4.18 (dd, 1H, J ¼ 3.3, 10.5 Hz, H₆), 4.26 4.37 (d, 1H, J ¼ 7.5 Hz, H⁰₁), 4.57–4.76 (m, 6H, BnH, H₁), 4.80–

(bd, 1H, J ¼ 7.9 Hz, H₄), 4.33 (dd, 1H, J ¼ 2.0, 4.5 Hz, H₂), 4.46– 4.90 (m, 4H), 5.03 (d, 1H, J ¼ 11.4 Hz, BnH), 5.10 (d, 1H, J ¼

4.65 (m, 5H, BnH, H⁰₁, H₃, H₆), 4.71–4.84 (m, 4H, BnH), 4.97 (d, 11.7 Hz, BnH), 7.19–7.44 (m, 35H, ArH). ¹³C NMR (CDCl₃, 75

1H, J ¼ 10.9 Hz, BnH), 5.07 (d, 1H, J ¼ 11.0 Hz, BnH), 5.58 (d, 1H, MHz): d 55.3, 68.1, 68.3, 70.1, 72.6, 73.2, 73.5, 73.7, 73.8, 74.8,

J ¼ 4.9 Hz, H₁), 7.14–7.44 (m, 20H, ArH). ¹³C NMR (CDCl₃, 100 75.3, 75.5, 77.3, 79.0, 80.1, 80.3, 82.5, 98.5 (C⁰₁), 102.9 (C₁),

MHz): d 24.5, 25.1, 26.1, 26.1, 67.4, 68.9, 69.8, 70.6, 70.9, 71.5, 127.0, 127.3, 127.4, 127.5, 127.53, 127.6, 127.67, 127.7, 127.8,

73.6, 74.4, 74.9, 75.1, 75.7, 77.8, 81.7, 84.6, 96.5 (C⁰₁), 104.5 (C₁), 127.9, 128.1, 128.16, 128.2, 128.3, 128.4, 138.2, 138.3, 138.6,

108.6 (CMe₂), 109.4 (CMe₂), 127.5, 127.6, 127.7, 127.8, 127.9, 138.7, 139.0, 139.1, 139.5. HRMS (ESI-TOF): calculated for

128.0, 128.3, 128.4, 128.7, 138.2, 138.8. HRMS (ESI-TOF):

calculated for C₄₆H₅₄O₁₁Na (M + Na) 805.3558 found 805.3559.

C₆₂H₆₆O₁₁Na (M + Na) 1009.4501 found 1009.4503.

Methyl 2,3,4,6-tetra-O-benzyl-b-^D-galactopyranosyl-(1/3)-2-O-

benzyl-4,6-O-benzylidene-a-^D-glucopyranoside (16)³⁷

2,3-Di-O-benzyl-4,6-O-benzylidene-b-^D-glucopyranosyl-(1/6)-

1,2:3,4-(di-O-isopropylidene)-a-^D-galactopyranose (11)³⁸

The crude residue was puried by silica gel (230–400 mesh)

The crude residue was puried by silica gel column chromatog- ash column chromatography (hexane/ethyl acetate, 4 : 1) to

raphy (60–120 mesh) and collected as colorless syrup (87%). R_f¼ aﬀord the compound 16 in 89% b as colorless syrup. R_f¼ 0.35

0.49 (hexane/ethyl acetate, 3/1); ¹H NMR (CDCl₃, 300 MHz) d 1.33 (hexane/ethyl acetate, 4.5/1); ¹H NMR (CDCl₃, 300 MHz): d 3.35

(s, 6H, CH₃), 1.46 (s, 3H, CH₃), 1.51 (s, 3H, CH₃), 3.40–3.50 (m, 2H), (s, 3H, OCH₃), 3.36–3.43 (m, 2H), 3.49 (dd, 1H, J ¼ 2.6, 9.7 Hz),

3.63–3.81 (m, 4H), 4.08–4.13 (m, 2H), 4.24 (bd, 1H, J ¼ 7.8 Hz, H₄), 3.59–3.72 (m, 4H), 3.76–3.88 (m, 3H), 4.19–4.37 (m, 4H), 4.46 (d,

4.31–4.37 (m, 2H), 4.57–4.61 (m, 2H, H₃, H⁰₁), 4.73–4.92 (m, 3H, 1H, J ¼ 3.7 Hz, H₁), 4.52 (d, 1H, J ¼ 12.1 Hz, BnH), 4.61 (d, 1H, J

BnH), 5.01 (d, 1H, J ¼ 11.0 Hz, BnH), 5.56 (s, 1H, PhCH), 5.57 (d, ¼ 11.4 Hz, BnH), 4.70 (bs, 2H, BnH), 4.74–4.82 (m, 3H, BnH,

1H, J ¼ 6.3 Hz, H₁), 7.26–7.48 (m, 15H, ArH). ¹³C NMR (CDCl₃, 75 H⁰₁), 4.94 (d, 1H, J ¼ 11.6 Hz, BnH), 5.04 (d, 1H, J ¼ 11.0 Hz,

MHz): d 24.5, 24.9, 26.0, 26.1, 66.0, 67.2, 68.8, 70.0, 70.5, 70.8, 71.4, BnH), 5.51 (s, 1H, PhCH), 7.19–7.48 (m, 30H, ArH). ¹³C NMR

74.8, 75.1, 77.2, 80.7, 81.4, 81.4, 81.6, 96.4 (C₁), 101.1 (PhCH), (CDCl₃, 125 MHz): d 55.2, 63.2, 68.7, 70.2, 70.7, 73.3, 73.5, 73.6,

104.9 (C⁰₁), 108.6 (CMe₂), 109.4 (CMe₂), 126.0, 127.5, 128.0, 128.2, 74.7, 75.0, 78.9, 79.5, 82.4, 98.2 (C⁰₁), 103.90 (C₁), 103.91 (PhCH)

128.3, 128.5, 128.9, 137.3, 138.6. HRMS (ESI-TOF): calculated for 127.4, 127.7, 127.8, 127.9, 128.0, 128.04, 128.13, 1228.26,

C₃₈H₄₃O₁₁Na (M + Na) 698.2703 and found 698.2781.

128.39, 128.42, 128.50, 128.55, 129.1, 129.8, 134.5, 136.6, 137.8,

138.4, 138.5, 138.6, 139.0. HRMS (ESI-TOF): calculated for

C

₅₅H₅₈O₁₁Na (M + Na) 917.3878 found 917.3877.

Methyl 2,3,4,6-tetra-O-benzyl-b-^D-galactopyranosyl-(1/6)-

2,3,4-tri-O-benzoyl-a-^D-glucopyranoside (13)³⁵

Methyl 2,3,4,6-tetra-O-benzyl-b-^D-galactopyranosyl-(1/2)-3-O-

benzyl-4,6-O-benzylidene-a-^D-glucopyranoside (18)³⁸

The crude mass was puried by silica gel column chromatog-

raphy (60–120 mesh) and collected as colorless syrup (95%).³⁵R_f

1

¼ 0.28 (hexane/ethyl acetate, 6/1); H NMR (CDCl₃, 300 MHz): The crude residue was puried by silica gel (230–400 mesh) ash

d 3.38 (s, 3H, OCH₃), 3.46–3.52 (m, 4H), 3.79–3.96 (m, 3H), 4.06– column chromatography (hexane/ethyl acetate, 4 : 1) to aﬀord the

4.09 (m, 2H), 4.31–4.41 (m, 2H), 4.49 (d, 1H, J ¼ 7.6 Hz, H⁰₁), compound 18 in 90% b as colorless syrup.³⁸R_f¼ 0.35 (hexane/

4.58–4.63 (m, 2H), 4.63–4.79 (m, 3H, BnH, H₁), 4.92 (d, 1H, J ¼ ethyl acetate, 4.5/1); ¹H NMR (CDCl₃, 300 MHz): d 3.45–3.47 (m,

11.7 Hz, BnH), 4.98 (d, 1H, J ¼ 11.0 Hz, BnH), 5.38 (app t, 1H, J ¼ 6H, OCH₃), 3.57–3.61 (m, 2H), 3.73–3.78 (m, 2H), 3.79–3.85 (m,

9.6, 9.9 Hz, H₄), 5.47 (t, 1H, J ¼ 9.6 Hz, H₂), 5.87 (t, 1H, J ¼ 3H), 3.81 (d, 1H, J ¼ 2.3 Hz), 4.36 (dd, 1H, J ¼ 4.9, 10.4 Hz, H₆),

9.6 Hz, H₃), 7.24–7.40 (m, 27H, ArH), 7.47–7.51 (m, 2H, ArH), 4.42 (bs, 2H), 4.51 (d, 1H, J ¼ 6.5 Hz, H⁰₁), 4.62 (d, 1H, J ¼ 11.6 Hz,

7.80–7.83 (d, 2H, J ¼ 7.1 Hz, ArH), 7.89–7.92 (d, 2H, J ¼ 8.0 Hz, BnH), 4.67–4.76 (m, 4H, BnH), 4.80 (d, 1H, J ¼ 4.8 Hz, H₁), 4.83 (d,

ArH), 7.96–7.98 (d, 2H, J ¼ 6.6 Hz, ArH). ¹³C NMR (CDCl₃, 125 1H, J ¼ 7.9 Hz, BnH), 4.94 (d, 1H, J ¼ 10.8 Hz, BnH), 4.95 (d, 1H, J

MHz): d 57.3, 68.7, 68.8, 70.2, 72.1, 73.1, 73.2, 73.4, 73.5, 73.56, ¼ 11.6 Hz, BnH), 5.56 (s, 1H, PhCH), 7.16–7.38 (m, 30H, ArH). ¹³

C

73.61, 74.5, 74.6, 75.1, 79.6, 82.1, 101.9 (C⁰₁), 104.3 (C₁), 127.5, NMR (CDCl₃, 75 MHz): d 56.7, 65.6, 68.7, 68.9, 72.9, 73.4, 73.5,

127.6, 127.7, 127.8, 127.9, 128.1, 128.2, 128.3, 128.42, 128.48, 73.7, 74.6, 74.9, 75.1, 79.3, 79.9, 81.3, 81.5, 82.5, 101.1 (PhCH),

128.5, 128.9, 129.0, 129.8, 129.9, 133.2, 137.9, 129.5, 138.5, 102.8 (C⁰₁), 103.4 (C₁), 126.0, 127.3, 127.5, 127.6, 127.7, 127.8,

138.7, 138.9, 165.3 (C]O), 165.6 (C]O), 165.9 (C]O). HRMS 128.0, 128.1, 128.2, 128.23, 128.3, 128.37, 128.4, 128.9, 137.4,

(ESI-TOF): calculated for C₆₂H₆₀O₁₄Na (M + Na) 1051.3881 137.9, 138.4, 138.5, 138.7, 138.9. HRMS (ESI-TOF): calculated for

found 1051.3880.

C₅₅H₅₈O₁₁Na (M + Na) 917.3878, found 917.3877.

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Methyl 2,3,4,6-tetra-O-benzyl-a-D-mannopyranosyl-(1/4)-

2,3,6-tri-O-benzyl-a-^D-glucopyranoside (20)^22b

Methyl 2,3,4-tri-O-acetyl-a-^L-rhamanopyranosyl-(1/3)-2-O-

benzoyl-4,6-O-benzylidene-a-^D-glucopyranoside (28)^22b

The crude mass was puried by silica gel column chromatog- The crude product was puried by silica gel (60–120 mesh)

raphy (60–120 mesh) and collected as colorless syrup (88%). R_fcolumn chromatography (PE/ethyl acetate 5 : 1) to aﬀord 28 in

1

¼ 0.48 (hexane/ethyl acetate, 3/1); H NMR (CDCl₃, 500 MHz): 89% as white solid.^22bR_f¼ 0.38 (hexane/ethyl acetate, 4/1); mp

d 3.32 (bs, 3H, OCH₃), 3.45–3.50 (m, 2H), 3.58 (dd, 1H, J ¼ 5.0, 162–164 ^ꢁC (from ethyl acetate–hexane); [a]²_D⁵+44 (c 1.0, CHCl₃);

11.0 Hz), 3.64–3.65 (m, 5H), 3.72–3.79 (m, 2H), 3.89 (t, 1H, J ¼ ¹H NMR (300 MHz, CDCl₃): d 0.75 (d, 3H, J ¼ 6.2 Hz, CH₃), 1.89

9.5 Hz), 4.13 (d, 1H, J ¼ 12.0 Hz, BnH), 4.23 (d, 1H, J ¼ 12.0 Hz, (s, 3H, COCH₃), 1.91 (s, 3H, COCH₃), 1.93 (s, 3H, COCH₃), 3.38

BnH), 4.34 (d, 1H, J ¼ 12.5 Hz, BnH), 3.35 (d, 1H, J ¼ 12.5 Hz, (s, 3H, OCH₃), 3.72 (t, 1H, J ¼ 9.4 Hz), 3.82 (t, 1H, J ¼ 10.2 Hz),

BnH), 4.42 (app t, 1H, J ¼ 9.0, 11.0 Hz, BnH), 4.47–4.54 (m, 7H, 3.94 (dt, 1H, J ¼ 4.6, 9.9 Hz, H₅), 4.16 (m, 1H, H⁰₅), 4.34 (dd, 1H, J

BnH, H⁰₁), 4.60 (d, 1H, J ¼ 12.0 Hz, BnH), 4.76 (d, 1H, J ¼ ¼ 4.5, 10.0 Hz, H₆), 4.42 (app t, 1H, J ¼ 9.3, 11.6 Hz, H₆), 4.89 (t,

10.5 Hz, BnH), 5.01 (d, 1H, J ¼ 11.5 Hz, BnH), 5.21 (d, 1H, J ¼ 1H, J ¼ 10.0 Hz, H⁰₄), 5.00 (s, 1H, H⁰₁), 5.04–5.09 (m, 3H, H₁, H₂,

2.0 Hz, H₁), 7.11–7.23 (m, 35H, ArH). ¹³C NMR (CDCl₃, 125 H⁰₂), 5.22 (dd, 1H, J ¼ 3.5, 10.0 Hz, H⁰₃), 5.59 (s, 1H, CHPh), 7.29–

MHz): d 55.2, 69.3, 69.8, 72.0, 72.2, 72.9, 73.1, 73.2, 73.3, 74.8, 7.59 (m, 8H, ArH), 7.98–8.01 (m, 2H, ArH). ¹³C NMR (CDCl₃, 75

74.9, 75.0, 76.2, 77.7, 79.9, 81.5, 97.6 (C⁰₁), 100.5 (C₁), 126.7, MHz): d 16.6, 20.4, 20.5, 20.6, 29.6, 55.4, 62.6, 66.2, 68.8, 68.9,

127.1, 127.2, 127.3, 127.5, 127.6, 127.7, 127.96, 127.98, 128.0, 69.4, 70.9, 73.2, 74.7, 79.5, 97.7, 98.0, 101.9 (PhCH) 126.3, 128.0,

128.1, 128.25, 128.27, 128.34, 128.38, 128.4, 137.8, 138.3, 138.4, 128.3, 129.1, 129.8, 133.3, 137.1, 165.6 (C]O), 169.2 (C]O),

138.6, 138.7, 138.8. HRMS (ESI-TOF): calculated for 169.8 (C]O). HRMS (ESI-TOF): calculated for C₃₃H₃₈O₁₄Na (M +

C

₆₃H₇₀O₁₁Na (M + Na) 1025.4816 and found 1025.4815.

Na) 658.2262 found 658.2261.

Methyl 2,3-di-O-benzyl-4,6-O-benzylidene-b-^D-

galactopyranosyl-(1/4)-2,3-O-isopropylidene-a-^L-

rhamnopyranoside (23)³⁹

Methyl 2-O-acetyl-3,4,6-tri-O-benzyl-a-^D-mannopyranosyl-(1/

4)-2,3,6-tri-O-benzyl-a-^D-mannopyranoside (31)^22d

The crude residue was directly puried by silica gel ash

The crude residue was puried by silica gel column chroma- column chromatography (hexane/ethyl acetate, 4 : 1) to aﬀord

tography (60–120 mesh) and collected as white foam (92%). R_f¼ 31 (91%) as a white foam.^22dR_f¼ 0.28 (25% ethyl acetate in

1

0.49 (hexane/ethyl acetate, 3/1); [a]²_D⁵¼ +8.0 (c, 1.0, CHCl₃); H hexane). [a]²_D⁶+28.2 (c 1.0, CHCl₃); H NMR (600 MHz, CDCl₃):

NMR (CDCl₃, 300 MHz) d 1.33 (s, 3H, CH₃), 1.37 (d, 3H, J ¼ d 2.01 (s, 3H, COCH₃), 3.35 (s, 3H, OCH₃), 3.43 (d, 1H, J ¼ 10.8

5.5 Hz, CH₃), 1.41 (s, 3H, CH₃), 3.29 (bs, 1H, H₂), 3.39 (s, 3H, Hz), 3.63 (dd, 1H, J ¼ 3.0, 10.8 Hz), 3.70–3.77 (m, 5H), 3.84–3.85

OCH₃), 3.58 (dd, 1H, J ¼ 3.6, 9.7 Hz), 3.65–3.74 (m, 2H), 3.78 (m, (m, 3H), 4.16 (t, 1H, J ¼ 9.0 Hz), 4.35 (d, 1H, J ¼ 12.0 Hz), 4.41

1H), 4.00 (bd, 1H, J ¼ 12.1 Hz), 4.05–4.10 (m, 2H), 4.23–4.33 (m, (brs, 1H), 4.43 (brs, 1H), 4.53–4.58 (m, 3H), 4.60–4.65 (m, 4H),

2H), 4.70–4.93 (m, 6H, BnH, H₁, H⁰₁), 5.48 (s, 1H, PhCH), 7.26– 4.67 (d, 1H, J ¼ 10.8 Hz), 4.76 (s, 1H, H₁), 4.80 (d, 1H, J ¼ 10.8

7.56 (m, 15H, ArH). ¹³C NMR (CDCl₃, 75 MHz): d 17.9, 26.3, 27.8, Hz), 5.42 (brs, 1H, H⁰₁), 5.47 (brs, 1H), 7.13–7.34 (m, 30H, ArH).

54.8, 66.3, 68.5, 69.2, 71.7, 73.5, 75.2, 76.2, 81.0, 98.1 (C⁰₁), 100.8 ¹³C NMR (150 MHz, CDCl₃): d 21.0, 54.9, 68.5, 68.6, 69.9, 71.4,

(C₁), 101.3 (PhCH), 109.1 (CMe₂), 126.1, 127.6, 127.9, 128.2, 71.1, 71.7, 72.3, 72.5, 73.2, 73.4, 73.9, 74.0, 75.0, 78.4, 80.1, 98.7

128.5, 128.9, 137.4, 137.8, 137.9. HRMS (ESI-TOF): calculated for (C₁), 99.4 (C⁰₁), 127.3, 127.4, 127.45, 127.5, 127.57, 127.6, 127.7,

C

₃₇H₄₄O₁₀Na (M + Na) 671.2832 found 671.2861.

127.8, 127.9, 128.0, 128.2, 128.27, 128.3, 137.9, 138.1, 138.2,

138.3, 138.4, 138.5, 169.9 (C]O); HRMS (ESI-TOF) : calculated

for C₅₇H₆₂O₁₂Na [M + Na]⁺961.4139 found 961.4131.

Methyl 2,3,4,6-tetra-O-acetyl-a-^D-mannopyranosyl-(1/3)-2-O-

benzoyl-4,6-O-benzylidene-a-^D-glucopyranoside (26)^22b

Methyl 2,3,4,6-tetra-O-benzoyl-b-^D-galactopyranosyl-(1/4)-

2,3,6-tri-O-benzyl-a-^D-mannopyranoside (33)

The crude residue was puried by column chromatography on

silica gel (60–120 mesh) using PE/ethyl acetate 4 : 1 to aﬀord 26

in 90% as white solid.^22bR_f¼ 0.29 (25% ethyl acetate in hexane). The crude product was puried by silica gel ash column chro-

[a]²_D⁶+28.2 (c 1.0, CHCl₃); H (300 MHz, CDCl₃): d 1.72 (s, 3H, matography (hexane/ethyl acetate, 4 : 1) to aﬀord 33 (91%) as

1

COCH₃), 1.92 (s, 3H, COCH₃), 2.04 (s, 3H, COCH₃), 2.07 (s, 3H, a white foam. R_f¼ 0.21 (25% ethyl acetate in hexane). [a]²_D⁶+59.5

COCH₃), 3.41 (s, 3H, OCH₃), 3.78–3.96 (m, 6H, H₃, H₄, H₅, H⁰₅, (c 1.06, CHCl₃); ¹H NMR (600 MHz, CDCl₃): d 3.25 (s, 3H, OCH₃),

H₆, H₆), 4.34 (dd, 1H, J ¼ 3.9, 9.9 Hz, H⁰₆), 4.45 (app t, 1H, J ¼ 9.2, 3.39 (d, 1H, J ¼ 9.6 Hz), 3.60–3.64 (m, 2H), 3.76 (t, 1H, J ¼ 2.4 Hz),

9.6 Hz, H⁰₆), 5.01 (d, 1H, J ¼ 5.9 Hz, H₁), 5.07–5.18 (m, 2H, H⁰₁, 3.90 (d, 1H, J ¼ 3.0 Hz), 3.94 (t, 1H, J ¼ 6.6 Hz), 4.26 (dd, 1H, J ¼

H⁰₄), 5.22 (dd, 1H, J ¼ 3.7, 9.8 Hz, H⁰₃), 5.34–5.36 (m, 2H, H₂, 8.0, 12.0 Hz), 4.37 (apparent t, 2H, J ¼ 9.0, 9.6 Hz), 4.40 (apparent

H⁰₂), 5.60 (s, 1H, CHPh), 7.27–7.60 (m, 8H, ArH), 8.08 (d, 2H, J ¼ t, 2H, J ¼ 4.8, 6.0 Hz), 4.61 (d, 1H, J ¼ 12.0 Hz), 4.67–4.73 (m, 3H,

6.5 Hz, ArH). ¹³C NMR (75 MHz, CDCl₃): d 20.4, 20.6, 20.7, 55.5, H₁), 4.92 (d, 1H, J ¼ 12.0 Hz), 4.99 (d, 1H, J ¼ 8.4 Hz, H⁰₁), 5.40

61.8, 62.1, 65.4, 68.3, 68.8, 69.0, 69.1, 71.7, 72.7, 77.4, 82.2, 97.8, (dd, 1H, J ¼ 3.6, 10.8 Hz), 5.72 (dd, 1H, J ¼ 8.4, 10.2 Hz), 5.87 (d,

101.3 (PhCH), 126.0, 128.1, 128.5, 128.9, 129.4, 129.8, 133.5, 1H, J ¼ 3.6 Hz), 7.17–7.57 (m, 27H, ArH), 7.76 (d, 2H, J ¼ 7.2 Hz,

136.8, 165.5 (C]O), 169.4 (C]O), 169.6 (C]O), 169.7 (C]O), ArH), 7.89 (d, 2H, J ¼ 7.8 Hz, ArH), 7.94 (d, 2H, J ¼ 7.8 Hz, ArH),

170.6 (C]O). HRMS (ESI-TOF): calculated for C₃₅H₄₀O₁₆Na [M + 7.97 (d, 2H, J ¼ 7.2 Hz, ArH). ¹³C NMR (150 MHz, CDCl₃): d 54.9,

Na]⁺716.2316, found 716.2317.

61.8, 68.8, 70.7, 71.2, 72.1, 72.7, 73.0, 73.5, 75.6, 78.5, 99.5 (C₁)

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101.2 (C⁰₁), 127.0, 127.4, 127.6, 127.9, 128.0, 128.4, 128.5, 128.6, 300 MHz): d 1.33 (s, 4H), 1.69 (s, 8H), 3.43 (d, 2H, J ¼ 3.43 Hz),

128.7, 129.0, 129.3, 129.4, 129.7, 129.9, 130.0, 133.26, 133.30, 3.54–3.66 (m, 5H), 3.75–3.87 (m, 4H), 3.94–4.01 (m, 2H), 4.05–

133.4, 133.5, 138.6, 139.3, 165.3 (C]O), 165.6 (C]O), 165.7 (C] 4.19 (m, 3H), 4.36 (m, 1H), 4.41–4.54 (m, 2H), 4.91 (d, 1H, J ¼ 8.3

O), 166.0 (C]O). HRMS (ESI-TOF): calculated for C₆₂H₅₈O₁₅Na Hz), 4.59 (m, 1H), 4.66–4.84 (m, 3H), 4.91 (d, 1H, J ¼ 8.3 Hz,

[M + Na]⁺1065.3673, found 1065.3665.

H⁰⁰₁), 5.38 (m, 1H), 5.44–5.53 (m, 2H), 5.87 (t, 1H, J ¼ 9.5 Hz),

7.15–7.49 (m, 29H, ArH), 7.81 (d, 2H, J ¼ 7.7 Hz, ArH), 7.92 (d,

2H, J ¼ 7.4 Hz, ArH), 7.97 (d, 2H, J ¼ 7.5 Hz, ArH). ¹³C NMR

(CDCl₃, 75 MHz): d 24.1, 24.8, 25.7, 25.9, 67.4, 68.6, 68.7, 68.8,

70.3, 70.4, 70.5, 70.8, 71.8, 73.2, 73.5, 74.0, 74.7, 74.8, 74.9, 75.6,

77.7, 82.1, 84.6, 96.1 (C₁), 101.3 (C⁰⁰₁), 103.9 (C⁰₁), 108.3 (CMe₂),

109.2 (CMe₂), 127.5, 127.6, 127.7, 127.8, 127.91, 127.97, 128.15,

128.19, 128.24, 128.3, 128.4, 128.5, 128.7, 128.9, 129.7, 129.8,

130.0, 132.9, 133.1, 133.3, 133.4, 138.0, 138.2, 138.7, 165.2 (C]

O), 165.4 (C]O), 165.8 (C]O); HRMS (ESI): calculated for

Methyl 2,3-di-O-benzoyl-4,6-O-benzylidene-b-^D-

glucopyranosyl-(1/6)-2,3,4-tri-O-benzoyl-a-^D-

glucopyranoside (35)^22b

The crude mass was puried by silica gel column chromatog-

raphy (60–120 mesh) (PE/EtOAc 5 : 1) to get pure product 35 in

88% yield. It was crystallized from PE/EtOAc; mp 232–234 ^ꢁC.

[a]²_D⁵+38.8 (c 1.39, CHCl₃). ¹H NMR (CDCl₃, 300 MHz): d 3.12 (s,

3H, OCH₃), 3.66–3.83 (m, 3H), 3.90 (app t, 1H, J ¼ 9.4, 9.7 Hz),

4.08 (bd, 1H, J ¼ 10.9 Hz), 4.21 (app t, 1H, J ¼ 8.0, 9.3 Hz, H₆), 4.42

(dd, 1H, J ¼ 4.6, 10.2 Hz, H₆), 4.91 (d, 1H, J ¼ 4.1 Hz, H₁), 4.93 (d,

1H, J ¼ 7.3 Hz, H⁰₁), 5.11 (dd, 1H, J ¼ 3.3, 10.2 Hz, H₂), 5.33 (ABq,

1H, J ¼ 9.7 Hz, H₃), 5.48–5.58 (m, 2H, CHPh, H⁰₂), 5.81 (t, 1H, J ¼

9.5 Hz, H⁰₃), 6.08 (t, 1H, J ¼ 9.8 Hz, H₄), 7.27–7.50 (m, 20H, ArH),

7.90 (d, 2H, J ¼ 8.5 Hz, ArH), 7.89–7.99 (m, 8H, ArH). ¹³C NMR (75

MHz, CDCl₃): d 55.0, 66.6, 68.5, 68.6, 69.6, 70.3, 71.9, 72.0, 72.4,

78.7, 96.4 (C⁰₁), 101.4 (PhCH), 102.0 (C₁) 126.1, 128.19, 128.16,

128.26, 128.29, 128.33, 128.4, 129.0, 129.3, 129.6, 129.77, 129.84,

133.0, 133.1, 133.2, 133.4, 136.7, 165.3 (C]O), 165.4 (C]O),

165.6 (C]O), 165.7 (C]O). HRMS m/z calculated for

(C₅₅H₄₈O₁₆Na⁺) [M + Na]⁺987.2840, found: 987.2841.

C

₇₃H₇₆O₁₉Na (M + Na) 1279.4879 found 1279.4870.

Methyl 3,4,6-tri-O-acetyl-2-deoxy-2-phathalimido-b-^D-

glucopyranosyl-(1/4)-[3,4,6-tri-O-acetyl-2-deoxy-2-

phathalimido-b-^D-glucopyranosyl-(1/6)]-2,3-di-O-benzyl-a-D-

glucopyranoside (42)^22d

The crude residue was puried by silica gel ash column

chromatography (hexane/EtOAc, 1 : 2) to aﬀord 42 (83%) as

a white foam. R_f0.31 (60% EtOAc in hexane). [a]²_D⁴+24.6 (c 1.0,

CHCl₃); lit.^22d[a]_D²⁰+23.9 (c 0.8, CHCl₃); ¹H NMR (500 MHz,

CDCl₃): d 1.80 (s, 3H, COCH₃), 1.84 (s, 3H, COCH₃), 1.97 (s, 3H,

COCH₃), 2.03 (s, 3H, COCH₃), 1.99 (s, 3H, COCH₃), 2.12 (s, 3H,

COCH₃), 3.06 (s, 3H, OCH₃), 3.17–3.19 (m, 2H), 3.40 (app t, 1H, J

¼ 9.0, 10.0 Hz), 3.52–3.59 (m, 2H), 3.66–3.68 (m, 2H), 3.76 (app t,

1H, J ¼ 8.5, 9.5 Hz), 3.84 (dd, 1H, J ¼ 2.5, 12.5 Hz), 4.08 (dd, 1H, J

¼ 4.0, 12.5 Hz), 4.11–4.20 (m, 4H), 4.34 (dd, 1H, J ¼ 5.0, 12.5 Hz),

4.41 and 4.53 (d, each 1H, J ¼ 12.0 Hz, BnH), 4.82 and 4.90 (d, J

¼ 12.0 Hz, each 1H, BnH), 5.05–5.12 (m, 3H), 5.47 (d, 1H, J ¼ 8.5

Hz), 5.52 (dd, 1H, J ¼ 9.5, 10.5 Hz), 5.69 (dd, 1H, J ¼ 9.5, 10.5

Hz), 7.15–7.16 (m, 2H, ArH), 7.21–7.26 (m, 4H, ArH), 7.32–7.33

(m, 4H, ArH), 7.65–7.67 (m, 2H, ArH), 7.75–7.79 (m, 4H, ArH),

7.87–7.88 (m, 2H, ArH). ¹³C NMR (125 MHz, CDCl₃): d 20.4, 20.5,

20.7, 20.8, 20.9, 54.58, 55.0, 55.4, 61.8, 62.2, 68.7, 68.8, 69.2,

69.3, 70.8, 70.85, 71.8, 73.3, 74.5, 77.3, 79.5, 79.8, 97.5, 97.6,

99.0, 123.5, 123.9, 126.8, 127.2, 127.9, 128.0, 128.3, 128.4, 131.4,

131.7, 134.2, 134.7, 138.1, 139.5, 169.5 (C]O), 170.2 (C]O),

170.8 (C]O), 170.9 (C]O). HRMS (ESI-TOF) calcd for

Methyl 2-O-acetyl-3-O-benzyl-4,6-O-benzylidene-b-^D-

glucopyranosyl-(1/6)-2,3,4-tri-O-benzoyl-a-^D-

glucopyranoside (37)^22d

The crude residue was puried by silica gel ash column

chromatography (hexane/EtOAc, 3 : 1) to aﬀord 37 (90%) as

a white solid. R_f0.30 (25% EtOAc in hexane); mp 185–186 C

ꢁ

(from PE–ethyl acetate); [a]²_D⁶+29.6 (c 1.0, CHCl₃); ¹H NMR (300

MHz, CDCl₃): d 2.07 (s, 3H, COCH₃), 3.42 (m, 1H), 3.46 (s, 3H,

OCH₃), 3.68 (dd, 1H, J ¼ 6.7, 10.8 Hz), 3.71–3.77 (m, 3H), 4.05

(dd, 1H J ¼ 1.5, 10.8 Hz), 4.25 (m, 1H), 4.31 (dd, 1H, J ¼ 4.9, 10.5

Hz), 4.54 (d, 1H, J ¼ 7.9 Hz, H⁰₁), 4.69 (d, 1H, J ¼ 12.1 Hz, BnH),

4.88 (d, 1H, J ¼ 12.1 Hz, BnH), 5.08 (dt, 1H, J ¼ 2.4, 7.6 Hz, H⁰₁),

5.23–5.27 (m, 2H, H₁, H₂), 5.45 (t, 1H, J ¼ 9.8 Hz, H₃), 5.55 (s, 1H,

PhCH), 6.15 (t, 1H, J ¼ 9.3 Hz, H₄), 7.26–7.31 (m, 7H, ArH), 7.35–

7.42 (m, 8H, ArH), 7.49–7.54 (m, 4H, ArH), 7.85–7.88 (m, 2H,

ArH), 7.94–7.99 (m, 4H, ArH). ¹³C NMR (75 MHz, CDCl₃): d 20.9,

C

₅₀H₄₈O₁₅Na [M + Na]⁺911.2891, found 911.2889.

55.4, 66.2, 68.3, 68.5, 69.4, 70.5, 72.0, 72.6, 74.1, 78.4, 81.4, 96.7, Methyl 2,3,4-tri-O-acetyl-a-^L-rhamanopyranosyl-(1/4)-[2,3,4-

101.2 (C₁), (PhCH), 101.8 (C₁), 126.0, 127.6, 127.8, 128.2, 128.3, tri-O-acetyl-a-^L-rhamanopyranosyl-(1/6)]-2,3-di-O-benzyl-a-

128.40, 128.43, 128.87, 128.99, 129.03, 129.6, 129.8, 129.9, D-glucopyranoside (43)^22b

133.0, 133.3, 133.5, 137.1, 138.2, 165.3 (C]O), 165.7 (C]O),

The crude product was puried by ash column chromatog-

165.8 (C]O), 169.4 (C]O); HRMS (ESI-TOF) calculated for

raphy on silica gel (230–400 mesh) using PE/EtOAc 2 : 1 to

C

₅₀H₄₈O₁₅Na [M + Na]⁺911.2891, found 911.2889.

aﬀord 43 in 81% as white foam. ¹H NMR (300 MHz, CDCl₃):

d 0.79 (d, 3H, J ¼ 6.2 Hz, CH₃), 1.20 (d, 3H, J ¼ 6.2 Hz, CH₃), 1.97

(s, 3H, COCH₃), 1.98 (s, 3H, COCH₃), 1.99 (s, 3H, COCH₃), 2.04

(s, 3H, COCH₃), 2.09 (s, 3H, COCH₃), 2.12 (s, 3H, COCH₃), 3.39

(s, 3H, OCH₃), 3.60 (dd, 1H, J ¼ 3.6, 9.4 Hz), 3.65–3.78 (m, 4H),

2,3,4,6-Tetra-O-benzyl-b-^D-glucopyranosyl-(1/6)-2,3,4-tri-O-

benzoyl-b-^D-glucopyranosyl-(1/6)-1,2:3,4-di-O-

isopropylidene-a-^D-galactopyranose (39)^19c

The crude residue was puried by silica gel ash column 3.83–3.95 (m, 3H), 4.00 (m, 1H), 4.57 (d, 1H, J ¼ 3.5 Hz, H₁), 4.59

chromatography (hexane/EtOAc, 3 : 1) to aﬀord 39 (89%) as (d, 1H, J ¼ 12.0 Hz, BnH), 4.62 (d, 1H, J ¼ 12.0 Hz, BnH), 4.72

1

a white foam. R_f0.30 (20% EtOAc in hexane); H NMR (CDCl₃, (app t, 1H, J ¼ 5.1, 5.7 Hz), 4.74 (d, 1H, J ¼ 11.9 Hz, BnH), 4.80

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(d, 1H, J ¼ 1.5 Hz, H⁰₁/H⁰⁰₁), 4.88 (d, 1H, J ¼ 1.5 Hz, H⁰⁰₁/H⁰₁), 4.97 75.17, 75.4, 75.8, 78.0, 83.0, 84.9, 104.3 (C₁) 124.6, 127.5, 127.6,

(d, 1H, J ¼ 10.1 Hz, BnH), 4.99–5.0 (m, 1H), 5.08 (d, 1H, J ¼ 127.7, 127.8, 128.1, 128.2, 128.3, 128.4, 128.5, 128.9, 132.0,

11.2 Hz, BnH), 5.13 (dd, 1H, J ¼ 1.7, 3.5 Hz), 5.22 (dd, 1H, J ¼ 138.3, 138.4, 138.8, 153.4. HRMS (ESI-TOF): calculated for

3.5, 10.2 Hz), 5.27 (dd, 1H, J ¼ 3.6, 6.5 Hz), 7.25–7.39 (m, 10H,

ArH).

C₄₂H₄₄O₆Na (M + Na) 667.3729, found 667.3731.

4⁰-Bromophenyl 2,3,4,6-tetra-O-benzyl-b-D-glucopyranoside (51)⁴¹

2⁰-Napthyl 2,3,4,6-tetra-O-benzyl-b-D-glucopyranoside (45)⁴⁰

A mixture of 1 (57 mg, 0.083 mmol), 44 (10 mg, 0.07 mmol) and

The crude residue was puried by silica gel (230–400 mesh)

ash column chromatography (hexane/ethyl acetate, 9.5 : 0.5)

to aﬀord the compound 51 in 92% b as white solid.⁴¹R_f¼ 0.54

(hexane/ethyl acetate, 9/1); ¹H NMR (CDCl₃, 500 MHz): 3.59–

3.79 (m, 6H), 4.52 (d, 1H, J ¼ 12.5 Hz, BnH), 4.56–4.60 (m, 2H,

BnH), 4.82–4.87 (m, 3H, BnH), 4.94–4.98 (m, 2H, BnH, H₁), 5.00

(d, 1H, J ¼ 11.0 Hz, BnH), 6.95–6.97 (d, 2H, J ¼ 8.5 Hz, ArH),

7.19–7.39 (m, 22H, ArH). ¹³C NMR (CDCl₃, 75 MHz): d 68.8, 73.5,

75.1, 75.3, 75.8, 77.7, 81.9, 84.7, 101.7 (C₁) 127.8, 127.9, 128.0,

128.2, 128.4, 128.5, 132.4, 137.9, 138.1, 138.2, 138.5, 156.5.

˚

ame activated 4 A molecular sieves were stirred in dry solvent

(4 mL) for 40 min at room temperature under argon atmo-

sphere. The mixture was cooled to ꢀ5 ^ꢁC and FeCl₃(1.3 mg,

0.0083 mmol) was added to it. Aer the acceptor was consumed

completely (checked by TLC) molecular sieves were ltered oﬀ

through celite bed. The ltrate was diluted with CH₂Cl₂and

washed subsequently with saturated NaHCO₃solution and

water. The organic layer was dried over anhydrous Na₂SO₄and

concentrated to aﬀord the glycosylated product. The crude

residue was directly puried by silica gel (230–400 mesh) ash

column chromatography (hexane/ethyl acetate, 8 : 1) to aﬀord

the compound 45 (44.86 mg) in 97% b as white foam.⁴⁰R_f¼ 0.42

(hexane/ethyl acetate, 4/1); ¹H (300 MHz, CDCl₃): d 3.72–3.86 (m,

6H), 4.52–4.62 (m, 3H, BnH), 4.82–4.89 (m, 3H, BnH), 4.97 (d,

1H, J ¼ 10.8 Hz, BnH), 5.11 (d, 1H, J ¼ 10.8 Hz, BnH), 5.16 (d,

1H, J ¼ 6.7 Hz, H₁), 7.23–7.45 (m, 24H, ArH), 7.66 (d, 1H, J ¼

7.7 Hz, ArH), 7.76–7.80 (m, 2H, ArH).

2⁰-Napthyl 2,3,4,6-tetra-O-benzyl-b-D-galactopyranoside (52)⁴⁰

The crude residue was puried by silica gel (230–400 mesh)

ash column chromatography (hexane/ethyl acetate, 8 : 1) to

aﬀord the compound 52 in 97% b as white foam.⁴⁰R_f¼ 0.42

(hexane/ethyl acetate, 4/1); ¹H (300 MHz, CDCl₃): d 3.60–3.71 (m,

3H), 3.77 (t, 1H, J ¼ 5.9 Hz), 3.98 (d, 1H, J ¼ 2.4 Hz), 4.19 (app t,

1H, J ¼ 8.0 Hz), 4.45 (ABq, 2H, J ¼ 11.6 Hz, BnH), 4.66 (d, 1H, J ¼

11.6 Hz, BnH), 4.76 (d, 1H, J ¼ 11.9 Hz, BnH), 4.81 (d, 1H, J ¼

11.9 Hz, BnH), 4.89 (d, 1H, J ¼ 11.8 Hz, BnH), 4.98–5.06 (app t,

2H, J ¼ 11.3, 13.2 Hz, BnH), 5.14 (d, 1H, J ¼ 7.6 Hz, H₁), 7.26–

7.37 (m, 22H, ArH), 7.42 (d, 2H, J ¼ 2.4 Hz, ArH), 7.64 (d, 1H, J ¼

7.9 Hz, ArH), 7.33–7.79 (m, 2H, ArH).

4⁰-Methoxyphenyl 2,3,4,6-tetra-O-benzyl-b-D-glucopyranoside

(47)⁴¹

The crude residue was puried by silica gel (230–400 mesh)

ash column chromatography (hexane/ethyl acetate, 9.5 : 0.5)

to aﬀord the compound 47 in 97% b as white solid.⁴¹R_f¼ 0.54

1⁰-Napthyl 2,3,4,6-tetra-O-benzyl-b-D-galactopyranoside (54)⁴⁰

1

(hexane/ethyl acetate, 9/1); H NMR (CDCl₃, 500 MHz): d 3.60

The crude residue was puried by silica gel (230–400 mesh)

ash column chromatography (hexane/ethyl acetate, 9 : 1) to

aﬀord compound 54 in 95% b as white foam.⁴⁰R_f¼ 0.62

(hexane/ethyl acetate, 4/1); ¹H (300 MHz, CDCl₃): d 3.61–3.69 (m,

2H), 3.71–3.78 (m, 2H), 4.00 (d, 1H, J ¼ 2.3 Hz), 4.32 (app t, 1H, J

¼ 7.8, 9.4 Hz), 4.40 (d, 1H, J ¼ 11.6 Hz, BnH), 4.47 (d, 1H, J ¼

11.7 Hz, BnH), 4.69 (d, 1H, J ¼ 11.6 Hz, BnH), 4.79 (s, 2H, BnH),

4.97 (d, 1H, J ¼ 10.6 Hz, BnH), 5.02 (d, 1H, J ¼ 11.6 Hz, BnH),

5.12 (d, 1H, J ¼ 10.6 Hz, BnH), 5.19 (d, 1H, J ¼ 7.7 Hz, H₁), 7.13

(d, 1H, J ¼ 7.6 Hz, ArH), 7.23–7.41 (m, 22H, ArH), 7.46 (d, 1H, J ¼

8.4 Hz, ArH), 7.52 (d, 1H, J ¼ 8.2 Hz, ArH), 7.80 (d, 1H, J ¼ 7.7 Hz,

ArH), 8.32 (d, 1H, J ¼ 8.1 Hz, ArH).

(m, 1H), 3.68–3.76 (m, 4H), 3.80 (s, 3H, OCH₃), 3.83 (dd, 1H, J ¼

1.0, 10.0 Hz), 4.55–4.64 (m, 3H, BnH, H₁), 4.84–4.93 (m, 4H,

BnH), 4.98 (d, 1H, J ¼ 11.0 Hz, BnH), 5.08 (d, 1H, J ¼ 11.0 Hz,

BnH), 6.84 (d, 2H, J ¼ 9.0 Hz, ArH), 7.06 (d, 2H, J ¼ 12.5 Hz, ArH),

7.22 (d, 2H, J ¼ 10.0 Hz, ArH), 7.27–7.38 (m, 18H, ArH). ¹³C NMR

(CDCl₃, 75 MHz): d 55.8, 69.1, 73.6, 75.1, 75.2, 75.9, 76.7, 77.9,

82.2, 84.8, 102.9 (C₁) 114.7, 118.6, 127.7, 127.7, 127.8, 127.8,

127.9, 128.0, 128.1, 128.2, 128.3, 128.4, 128.5, 138.2, 138.3,

138.4, 138.7, 151.7, 155.4. HRMS (ESI-TOF): calculated for

C

₄₁H₄₂O₇Na (M + Na) 669.2823 found 669.2841.

2⁰,6⁰-Dimethylphenyl 2,3,4,6-tetra-O-benzyl-b-D-

glucopyranoside (49)⁴⁰

4⁰-Chloro-3⁰-methylphenyl 2,3,4,6-tetra-O-benzyl-b-D-

galactopyranoside (56)

The crude residue was puried by silica gel (230–400 mesh)

ash column chromatography (hexane/ethyl acetate, 9.5 : 0.5)

to aﬀord the compound 49 in 90% b as white solid.⁴⁰R_f¼ 0.52 The crude residue was puried by silica gel (230–400 mesh)

(hexane/ethyl acetate, 9/1); [a]²_D⁷+96.4 (c 1, CHCl₃); ¹H NMR ash column chromatography (hexane/ethyl acetate, 9 : 1) to

(CDCl₃, 400 MHz): d 2.39 (s, 6H, 2 ꢃ CH₃), 3.32 (m, 1H, H₅), aﬀord the compound 56 in 94% b as white solid. R_f¼ 0.62

1

3.65–3.77 (m, 5H), 4.46 (d, 1H, J ¼ 12.4 Hz, BnH), 4.54 (d, 1H, J ¼ (hexane/ethyl acetate, 4/1); [a]²_D⁵ꢀ20.84 (c 1.9, CHCl₃); H (300

12.0 Hz, BnH), 4.62 (d, 1H, J ¼ 10.8 Hz, BnH), 4.79–4.89 (m, 4H, MHz, CDCl₃): d 2.28 (s, 3H, CH₃), 3.59–3.67 (m, 4H), 3.94 (bd,

BnH, H₁), 5.01 (d, 1H, J ¼ 10.8 Hz, BnH), 5.16 (d, 1H, J ¼ 10.8 Hz, 1H, J ¼ 2.6 Hz), 4.09 (dd, 1H, J ¼ 7.8, 9.5 Hz), 4.37–4.48 (2d, 2H, J

BnH), 6.98–7.04 (m, 3H, ArH), 7.20 (d, 1H, J ¼ 1.2 Hz, ArH), 7.21 ¼ 11.0 Hz, BnH), 4.63 (d, 1H, J ¼ 11.6 Hz, BnH), 4.71–4.80 (2d,

(d, 1H, J ¼ 2.0 Hz, ArH), 7.25–7.33 (m, 16H, ArH), 7.38–7.40 (m, 2H, J ¼ 11.0 Hz, BnH), 4.85 (d, 1H, J ¼ 10.9 Hz, BnH), 4.91 (d,

2H, ArH). ¹³C NMR (CDCl₃, 125 MHz): d 17.3, 69.1, 73.6, 75.10, 1H, J ¼ 7.7 Hz, H₁), 4.96 (d, 1H, J ¼ 10.8 Hz, BnH), 4.98 (d, 1H, J

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¼ 11.6 Hz, BnH), 6.83–7.36 (m, 23H, ArH). ¹³C NMR (CDCl₃, 125 12.0 Hz, BnH), 4.75 (d, 1H, J ¼ 11.0 Hz, BnH), 4.82 (d, 1H, J ¼

MHz): d 20.4, 69.1, 73.3, 73.5, 73.8, 74.1, 74.7, 75.6, 79.3, 82.2, 11.0 Hz, BnH), 4.94–4.98 (m, 3H, H₁, H⁰₁, H₂), 5.08 (bs, 2H, BnH),

102.3 (C₁), 115.9, 119.7, 127.72, 127.78, 127.8, 127.9, 127.98, 5.29 (bs, 1H, NH), 7.19–7.36 (m, 35H, ArH). ¹³C NMR (75 MHz,

128.3, 128.4, 128.5, 128.6, 129.7, 137.1, 137.9, 138.5, 138.6, CDCl₃): d 20.9, 29.5, 38.2, 66.5, 66.7, 68.1, 68.3, 72.5, 72.6, 73.1,

156.1. HRMS (ESI): calculated for C₄₁H₄₁ClO₆Na (M + Na) 73.5, 73.7, 74.3, 74.7, 75.3, 79.9, 80.8, 82.5, 100.8 (C₁), 102.9

664.2592, found 664.2491.

(C⁰₁), 127.2, 127.4, 127.5, 127.57, 127.62, 127.7, 127.9, 128.0,

128.1, 128.2, 128.3, 128.3, 128.4, 128.5, 136.9, 138.1, 128.2,

138.5, 138.8, 139.0, 139.1, 156.6 (C]O), 169.6 (C]O). HRMS

(TOF): calc. for (M + Na)⁺C₆₇H₇₃NO₁₄Na 1138.4929, found

1138.4932.

2⁰,6⁰-Dimethylphenyl 2,3,4,6-tetra-O-benzyl-b-D-

galactopyranoside (57)⁴¹

The crude residue was puried by silica gel (230–400 mesh)

ash column chromatography (hexane/ethyl acetate, 9.5 : 0.5)

to aﬀord the compound 57 in 91% b as white solid.⁴¹R_f¼ 0.52

(hexane/ethyl acetate, 9/1); ¹H NMR (CDCl₃, 300 MHz): d 2.35 (s,

6H, 2 ꢃ CH₃), 3.41–3.52 (m, 2H), 3.57–3.65 (m, 2H), 3.93 (bd,

1H, J ¼ 2.5 Hz), 4.11 (dd, 1H, J ¼ 7.7, 9.7 Hz), 4.35 (bs, 2H, BnH),

4.64 (d, 1H, J ¼ 11.7 Hz, BnH), 4.72–4.82 (m, 3H, BnH, H₁), 4.89

(d, 1H, J ¼ 10.9 Hz, BnH), 5.00 (d, 1H, J ¼ 11.7 Hz, BnH), 5.10 (d,

1H, J ¼ 10.9 Hz, BnH), 6.93–7.02 (m, 2H, ArH), 7.16–7.19 (m, 2H,

ArH), 7.26–7.29 (m, 19H, ArH).

Adamentyl 2,3,4,6-tetra-O-benzoyl-b-^D-glucopyranoside (64)⁴²

The crude mass was puried by silica gel column chromatog-

raphy (60–120 mesh) (PE/EtOAc 5 : 1) to get pure product (64) as

colourless syrup in 94% yield. ¹H NMR (CDCl₃, 300 MHz):

d 1.49–1.61 (m, 6H), 1.66–1.70 (m, 3H), 1.83–1.87 (m, 3H), 2.04

(s, 3H), 4.22 (m, 1H, H₅), 4.52–4.60 (m, 2H, H₆, H₆), 5.16 (d, 1H, J

¼ 7.9 Hz, H₁), 5.49–5.62 (m, 2H, H₂, H₄), 5.95 (t, 1H, J ¼ 9.6 Hz,

H₃), 7.28–7.55 (m, 12H, ArH), 7.85–8.06 (m, 8H, ArH).

3-(N-Benzyloxycarbonyl)propyl 2,3,4,6-tetra-O-benzoyl-b-^D-

galactopyranoside (60)^22b

Adamentyl 2,3,4,6-tetra-O-benzoyl-b-^D-galactopyranoside (65)

The crude product was puried by column chromatography

on silica gel (60–120 mesh) using PE/EtOAc 6 : 1 to give 60 in

88% as white foam; [a]²_D⁵+60.05 (c 1.28, CHCl₃); ¹H NMR

(CDCl₃, 500 MHz): d 1.77–1.88 (m, 2H, CH₂), 3.15–3.27 (m, 2H,

NCH₂), 3.67 (m, 1H, OCH), 4.03 (m, 1H, H₅), 4.32 (t, 1H, J ¼

6.5 Hz, OCH), 4.42 (dd, 1H, J ¼ 6.8, 11.8 Hz, H₆), 4.67 (dd, 1H, J

¼ 6.5, 11.5 Hz, H₆), 4.81 (d, 1H, J ¼ 7.5 Hz, H₁), 5.00 (m, 1H,

NH), 5.05 (s, 2H, BnH), 5.62 (dd, 1H, J ¼ 3.8, 10.3 Hz, H₃), 5.78

(dd, 1H, J ¼ 8.3, 10.3 Hz, H₂), 5.99 (d, 1H, J ¼ 3.5 Hz, H₄), 7.21–

7.26 (m, 2H, ArH), 7.29 (m, 1H, ArH), 7.33–7.36 (m, 6H, ArH),

7.41–7.44 (m, 3H, ArH), 7.46–7.51 (m, 3H, ArH), 7.55 (t, 1H, J ¼

7.5 Hz, ArH), 7.62 (t, 1H, J ¼ 7.5 Hz, ArH), 7.77–7.79 (d, 2H, J ¼

8.0 Hz, ArH), 7.94–7.95 (d, 2H, J ¼ 8.0 Hz, ArH), 8.00–8.02 (m,

2H, ArH), 8.08–8.09 (d, 2H, J ¼ 8.0 Hz, ArH); ¹³C NMR (125

MHz, CDCl₃): d 29.7, 38.3, 62.2, 66.6, 68.3, 70.0, 71.6, 71.7,

101.8 (C₁), 128.1, 128.4, 128.6, 128.8, 128.9, 129.2, 129.4,

The crude mass was puried by silica gel column chroma-

tography (60–120 mesh) (PE/EtOAc 5 : 1) to get pure product

(65) as colourless syrup in 89% yield. ¹H NMR (CDCl₃, 300

MHz): d 1.49–1.56 (m, 6H), 1.64–1.71 (m, 3H), 1.84–1.87 (m,

3H), 2.04 (s, 3H), 4.34 (m, 1H, H₅), 4.46 (dd, 1H, J ¼ 5.9,

11.0 Hz, H₆), 4.59 (dd, 1H, J ¼ 3.1, 10.8 Hz, H₆), 5.09 (d, 1H, J ¼

7.9 Hz, H₁), 5.60 (dd, 1H, J ¼ 3.1, 10.2 Hz, H₃), 5.78 (app t, 1H, J

¼ 8.2, 9.8 Hz, H₂), 5.97 (bs, 1H, H₄), 7.23–7.59 (m, 12H, ArH),

7.78–7.80 (d, 2H, J ¼ 7.7 Hz, ArH), 7.95–7.98 (d, 2H, J ¼ 7.5 Hz,

ArH), 8.03–8.06 (d, 2H, J ¼ 7.6 Hz, ArH), 8.10–8.13 (d, 2H, J ¼

7.6 Hz, ArH). ¹³C NMR (CDCl₃, 75 MHz): d 30.6, 36.1, 42.4,

62.5, 68.4, 69.9, 71.2, 72.2, 75.8, 94.6 (C₁) 128.3, 128.37,

128.42, 128.6, 128.9, 129.1, 129.67, 129.72, 129.8, 130.2, 133.1,

133.2, 133.5, 165.6, 165.8, 166.1.

129.6, 129.8, 129.9, 130.2, 133.4, 133.5, 133.7, 156.6 (C]O), Methyl 2,3,4,6-tetra-O-acetyl-b-^D-glucopyranosyl-(1/4)-2,3,6-

165.7 (C]O), 166.2 (C]O); HRMS m/z calcd for tri-O-benzyl-a-^D-glucopyranoside (67)^22d

C

₄₅H₄₁NO₁₂Na⁺calcd: 810.2527, found: 810.2526.

The crude mass was puried by silica gel column chromatog-

raphy (60–120 mesh) (PE/EtOAc 5 : 1) to get pure product (67) as

colourless syrup in 91% yield. ¹H NMR (CDCl₃, 500 MHz): d 1.92

(s, 6H, COCH₃), 1.95 (s, 3H, COCH₃), 1.97 (s, 3H, COCH₃), 3.28

(m, 1H), 3.34 (s, 3H, OCH₃), 3.44 (dd, 1H, J ¼ 4.0, 9.0 Hz), 3.56–

3-(N-Benzyloxycarbonyl)propyl 2,3,4,6-tetra-O-benzyl-b-^D-

galactopyranosyl-(1/4) 2-O-acetyl-3,6-di-O-benzyl-b-^D-

glucopyranoside (62)^22e

The crude mass was puried by silica gel column chromatog- 3.60 (m, 2H), 3.73 (dd, 1H, J ¼ 3.5, 11.0 Hz), 3.81–3.86 (m, 3H),

raphy (60–120 mesh) (PE/EtOAc 3 : 1) to get pure product (62) as 4.11 (dd, 1H, J ¼ 4.0, 12.0 Hz), 4.40 (d, 1H, J ¼ 12.0 Hz, BnH),

colourless syrup in 92% yield. [a]²_D⁹ꢀ2.57 (c 7.0, CHCl₃); ¹H 4.48 (d, 1H, J ¼ 8.0 Hz, H⁰₁), 4.55 (d, 1H, J ¼ 3.5 Hz, H₁), 4.56 (d,

NMR (500 MHz, CDCl₃): d 1.68–1.76 (m, 2H, CH₂), 1.97 (s, 3H, 1H, J ¼ 12.5 Hz, BnH), 4.71 (app t, 3H, J ¼ 11.0, 12.0 Hz, BnH),

COCH₃), 3.23 (m, 1H, NCH), 3.33–3.37 (m, 3H), 3.38–3.43 (m, 4.86 (app t, 1H, J ¼ 8.0, 9.0 Hz, H⁰₂), 4.91–5.00 (m, 3H, BnH, H⁰₃,

2H), 3.46 (m, 1H), 3.55–3.59 (m, 2H), 3.69 (d, 1H, J ¼ 10.0 Hz), H⁰₄), 7.21–7.27 (m, 8H, ArH), 7.33–7.39 (m, 7H, ArH). ¹³C NMR

3.74–3.77 (m, 2H), 3.85 (m, 1H), 3.9 (d, 1H, J ¼ 2.5 Hz), 3.95 (t, (CDCl₃, 75 MHz): d 20.6 (COCH₃), 20.7 (COCH₃), 55.4, 67.6, 68.1,

1H, J ¼ 9.0 Hz), 4.23 (d, 1H, J ¼ 12.0 Hz), 4.29–4.34 (app t, 2H, J 69.7, 71.5, 71.9, 73.2, 73.5, 73.7, 75.2, 78.9, 79.9, 98.4 (C₁), 100.0

¼ 10.5, 11.5 Hz), 4.36–4.38 (dd, 2H, J ¼ 1.5, 9.0 Hz), 4.48 (d, 1H, J (C⁰₁), 127.2, 127.4, 127.8, 128.1, 128.2, 128.22, 128.4, 128.7,

¼ 12.0 Hz, BnH), 4.54 (d, 1H, J ¼ 11.0 Hz, BnH), 4.58 (d, 1H, J ¼ 137.7, 138.3, 139.4, 169.1 (C]O), 169.4 (C]O), 170.2 (C]O),

11.0 Hz, BnH), 4.68 (d, 1H, J ¼ 12.0 Hz, BnH), 4.72 (d, 1H, J ¼ 170.7 (C]O).

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aﬀord the compound 76 in 94% b as colourless syrup.^33dR_f0.35

(25% EA in hexane); ¹H NMR (CDCl₃, 300 MHz): d 3.24 (m, 1H),

3.38–3.54 (m, 4H), 3.60–3.78 (m, 4H), 3.90 (dd, 1H, J ¼ 3.2, 10.9

Hz), 4.04 (t, 1H, J ¼ 9.5 Hz), 4.23 (dd, 1H, J ¼ 4.9, 10.4 Hz), 4.45

(d, 1H, J ¼ 11.9 Hz), 4.58–4.67 (m, 3H), 4.74–4.87 (m, 6H), 4.94

(d, 1H, J ¼ 11.3 Hz), 5.01 (d, 1H, J ¼ 10.7 Hz), 5.53 (s, 1H, PhCH),

7.27–7.61 (m, 35H, ArH). ¹³C NMR (CDCl₃, 75 MHz): d 62.4, 68.2,

70.7, 73.4, 74.9, 75.3, 75.5, 75.6, 76.6, 79.3, 82.5, 84.8, 87.5 (C₁),

101.4 (PhCH), 102.6 (C⁰₁), 126.1, 127.3, 127.5, 127.6, 127.7,

127.8, 127.9, 127.98, 128.2, 128.3, 128.4, 128.6, 128.9, 129.0,

129.7, 132.1, 138.2, 138.5. HRMS (ESI-TOF): calculated for

4-Methoxyphenyl 2,3,4-tri-O-benzoyl-a-D-rhamnopyranosyl-

(1/3)-2,4-di-O-benzoyl-a-^D-rhamnopyranoside (70)⁴³

The residue was puried by ash column chromatography (PE/

EtOAc, 4 : 1) to aﬀord the title compound 70 as colorless syrup

(91%); ¹H NMR (CDCl₃, 300 MHz): d 1.20 (d, 3H, J ¼ 5.7 Hz), 1.37

(d, 3H, J ¼ 6.0 Hz, CH₃), 3.81 (s, 3H, OCH₃), 4.18–4.28 (m, 2H),

4.72 (bd, 1H, J ¼ 9.6 Hz), 5.34 (bs, 2H), 5.54 (app t, 1H, J ¼ 9.6,

10.0 Hz), 5.63–5.67 (m, 2H), 5.71–5.74 (m, 2H), 6.88–6.90 (d, 2H,

J ¼ 7.2 Hz, ArH), 7.09–7.11 (m, 2H, ArH), 7.20–7.25 (t, 1H, J ¼

7.2 Hz, ArH), 7.28–7.37 (m, 3H, ArH), 7.39–7.51 (m, 7H, ArH),

7.61–7.63 (m, 3H, ArH), 7.68 (d, 1H, J ¼ 6.2 Hz, ArH), 7.72–7.78

(app t, 4H, J ¼ 8.1, 8.5 Hz, ArH), 7.94–7.96 (d, 2H, J ¼ 6.2 Hz,

ArH), 8.15–8.18 (d, 2H, J ¼ 7.8 Hz, ArH), 8.28–8.31 (d, 2H, J ¼

7.8 Hz, ArH).

C

₆₀H₆₀O₁₀SNa (M + Na) 995.3805 and found 995.3810.

Phenyl 2-O-acetyl-3,4,6-tri-O-benzyl-a-^D-mannopyranosyl-(1/

6)-2,3,4-tri-O-benzoyl-1-thio-a-^D-mannopyranoside (79)^22d

Methyl 2-O-acetyl-3,4,6-tri-O-benzyl-a-^D-mannopyranosyl-(1/

2)-3,4,6-tri-O-benzyl-a-^D-mannopyranosyl-(1/2)-3,4,6-tri-O-

benzyl-a-^D-mannopyranoside (73)^22f

The crude residue was puried by silica gel ash column

chromatography (hexane/ethyl acetate, 3 : 1) to aﬀord 79 (94%)

as a white foam.^22dR_f¼ 0.25 (30% ethyl acetate in hexane);

[a]²_D⁶+16.3 (c 1.34, CHCl₃); ¹H NMR (600 MHz, CDCl₃): d 2.10 (s,

3H, COCH₃), 3.53 (d, 1H, J ¼ 9.6 Hz), 3.68 (m, 1H), 3.69 (m, 1H),

3.75 (dd, 1H, J ¼ 3.0, 10.2 Hz), 3.87 (t, 1H, J ¼ 9.6 Hz), 3.95 (dd,

1H, J ¼ 3.6, 9.6 Hz), 4.00 (dd, 1H, J ¼ 5.4, 10.8 Hz), 4.32 (d, 1H, J

¼ 10.8 Hz), 4.36 (d, 1H, J ¼ 12.0 Hz), 4.44 (d, 1H, J ¼ 10.8 Hz),

4.50 (d, 1H, J ¼ 10.8 Hz), 4.58 (d, 1H, J ¼ 12.0 Hz), 4.81 (m, 1H),

4.84 (d, 1H, J ¼ 10.8 Hz), 4.87 (d, 1H, J ¼ 1.3 Hz, H⁰₁), 5.36 (dd,

1H, J ¼ 1.8, 3.0 Hz), 5.73 (d, 1H, J ¼ 1.2 Hz, H₁), 5.81 (dd, 1H, J ¼

3.0, 9.6 Hz), 5.94 (m, 1H), 5.99 (t, 1H, J ¼ 10.2 Hz), 7.13–7.16 (m,

3H, ArH), 7.22–7.35 (m, 17H, ArH), 7.41–7.57 (m, 9H, ArH), 7.85

(d, 2H, J ¼ 7.2 Hz, ArH), 8.00 (d, 2H, J ¼ 7.2 Hz, ArH), 8.07 (d, 2H,

J ¼ 7.2 Hz, ArH). ¹³C NMR (150 MHz, CDCl₃): d 21.0, 66.6, 67.3,

68.44, 68.46, 70.45, 70.48, 71.5, 71.8, 72.0, 73.2, 74.0, 75.1, 78.4,

86.0 (C₁) 98.0 (C⁰₁) 127.50, 127.51, 127.7, 127.88, 127.90, 128.0,

128.18, 128.23, 128.27, 128.32, 128.4, 128.47, 128.54, 128.6,

128.9, 129.2, 129.3, 129.4, 129.71, 129.8, 129.74, 129.89, 129.9,

131.5, 132.1, 133.22, 133.25, 133.5, 133.6, 137.9, 138.0, 138.5,

165.3 (C]O), 165.4 (C]O), 170.3 (C]O); HRMS (ESI-TOF):

calculated for C₆₂H₅₈O₁₄SNa [M + Na]⁺1081.3445 found

1081.3441.

The residue was puried by ash column chromatography (PE/

EtOAc, 4 : 1) to aﬀord the title compound 73 as colorless syrup

(90%); [a]²_D⁵+10.2 (c 1.5, CHCl₃); ¹H NMR (300 MHz, CDCl₃):

d 2.14 (s, 3H, COCH₃), 3.23 (s, 3H, OCH₃), 3.53 (d, 1H, J ¼ 10.5

Hz) 3.65–3.84 (m, 9H), 3.87–3.93 (m, 4H), 3.95–3.99 (m, 2H),

4.11 (bs, 1H), 4.32 (d, 1H, J ¼ 12.1 Hz, BnH), 4.41–4.47 (m, 2H),

4.51–4.67 (m, 11H), 4.70 (d, 1H, J ¼ 3.3 Hz), 4.81–4.87 (m, 4H),

5.06 (brs, 1H), 5.21 (brs, 1H), 5.55 (bs, 1H, H⁰⁰₂), 7.15–7.36 (m,

45H, ArH); ¹³C NMR (75 MHz, CDCl₃): d 21.2 (COCH₃), 54.7

(OCH₃), 68.8, 69.6, 71.7, 71.9, 72.1, 72.2, 73.3, 73.4, 74.3, 74.9,

75.0, 75.1, 78.1, 79.3, 79.5, 99.4, 99.8, 100.6, 127.4, 127.5, 127.6,

127.7, 127.8, 127.9, 128.0, 128.16, 128.23, 128.3, 128.4, 138.1,

138.2, 138.4, 138.5, 138.6, 170.1 (C]O).

Phenyl 2,3,4,6-tetra-O-benzyl-b-^D-glucopyranosyl-(1/4)-2,3,6-

tri-O-benzyl-1-thio-b-^D-glucopyranoside (75)^33c

The crude residue was puried by silica gel (230–400 mesh)

ash column chromatography (hexane/ethyl acetate, 4 : 1) to

aﬀord the compound 75 in 85% b only as white solid,^33cR_f0.33

(20% EA in hexane); mp 146–148 C (from MeOH), lit.^33cmp

ꢁ

147–148 ^ꢁC, [a]_D²⁵+11.8 (c 1.05, CHCl₃); lit.^33c[a]²_D⁴+10.4 (c 1.08,

CHCl₃). ¹H NMR (CDCl₃, 300 MHz): d 3.37–3.52 (m, 4H), 3.57–

3.92 (m, 7H), 4.08 (appatent t, 1H, J ¼ 9.2, 9.5 Hz), 4.43 (bs,

2H), 4.48–4.68 (m, 5H), 4.72–4.86 (m, 7H), 4.93 (d, 1H, J ¼

10.8 Hz, BnH), 5.17 (d, 1H, J ¼ 11.1 Hz, BnH), 7.19–7.34 (m,

38H, ArH), 7.58–7.61 (m, 2H, ArH). ¹³C NMR (CDCl₃, 75 MHz):

d 68.3, 68.9, 73.2, 73.3, 74.8, 75.0, 75.5, 75.7, 76.4, 78.1, 80.2,

82.8, 85.0, 87.5 (C₁), 102.6 (C⁰₁), 127.3, 127.4, 127.5, 127.6,

127.7, 127.9, 128.0, 128.1, 128.2, 128.3, 128.33, 128.4, 128.9,

132.1, 133.8, 138.2, 138.3, 138.4, 138.5, 138.6, 139.2. HRMS

(ESI-TOF): calculated for C₆₇H₆₈O₁₀SNa (M + Na) 1087.4431

and found 1087.4414.

Phenyl 2-O-benzoyl-3,4-di-O-benzyl-a-^L-rhamnopyranosyl-(1/

2)-3,4-di-O-benzyl-1-thio-a-^L-rhamnopyranoside (82)

The crude residue was puried by silica gel ash column

chromatography (hexane/ethyl acetate, 9 : 1) to aﬀord 82 (92%)

1

as a white foam. R_f¼ 0.25 (10% ethyl acetate in hexane); H

NMR (300 MHz, CDCl₃): d 1.32 (d, 3H, J ¼ 5.8 Hz, CH₃), 1.36 (d,

3H, J ¼ 6.1 Hz, CH₃), 3.53–3.61 (m, 2H, H₄, H⁰₄), 3.89–3.93 (m,

2H, H₃, H⁰₅), 4.11–4.19 (m, 2H, H₅, H⁰₃), 4.25 (bs, 1H, H₂), 4.62–

4.69 (m, 3H, BnH), 4.73–4.76 (m, 2H, BnH), 4.85–4.99 (m, 3H,

BnH), 5.12 (bs, 1H, H₁), 5.51 (bs, 1H, H⁰₁), 5.80 (bs, 1H, H⁰₂),

7.24–7.64 (m, 28H, ArH), 8.13–8.15 (d, 2H, J ¼ 7.1 Hz, ArH). ¹³

C

NMR (75 MHz, CDCl₃): d 18.0 (CH₃), 18.1 (CH₃), 68.5, 69.4, 69.5,

71.7, 74.4, 75.4, 77.8, 80.7, 80.1, 80.2, 87.3 (C₁), 99.7 (C⁰₁), 127.3,

127.6, 127.7, 127.8, 128.1, 128.2, 128.3, 128.4, 128.5, 128.6,

Phenyl 2,3-di-O-benzyl-4,6-O-benzyledene-b-^D-glucopyranosyl-

(1/4)-2,3,6-tri-O-benzyl-1-thio-b-^D-glucopyranoside (76)^33d

The crude residue was puried by silica gel (230–400 mesh) 129.1, 129.9, 130.1, 131.3, 133.2, 134.6, 138.1, 138.1, 138.4,

ash column chromatography (hexane/ethyl acetate, 3 : 1) to 138.5, 165.6 (C]O).

RSC Adv., 2016, 6, 105589–105606 | 105603

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11.5 Hz, H₆), 4.14–4.18 (m, 2H, H₅, H₆), 4.46 (d, 1H, J ¼ 7.9 Hz,

H⁰₁), 4.52–4.62 (m, 3H, 3 ꢃ BnH), 4.78–4.97 (m, 4H, 3Bn ꢃ H,

H₁), 5.49 (t, 1H, J ¼ 9.6 Hz, H₄), 5.56 (t, 1H, J ¼ 7.9 Hz, H₂), 5.96

(t, 1H, J ¼ 9.6 Hz, H₃), 7.20–7.23 (m, 2H, ArH), 7.28–7.45 (m,

20H, ArH), 7.52–7.57 (t, 2H, J ¼ 7.3 Hz, ArH), 7.86–7.88 (t, 2H, J ¼

7.6 Hz, ArH), 7.97–8.04 (m, 4H, ArH). ¹³C NMR (CDCl₃, 75 MHz):

d 57.2, 60.5, 70.1, 72.0, 73.1, 73.5, 74.2, 74.8, 75.0, 75.6, 77.5,

84.2, 84.7, 102.0 (J_C-H¼ 155.9 Hz, C⁰₁) 104.1 (J_C-H¼ 157.1 Hz,

C₁), 127.6, 127.7, 127.77, 127.82, 127.98, 128.01, 128.3, 128.39,

128.42, 128.5, 128.9, 129.4, 129.8, 129.9, 133.2, 133.5, 138.1,

138.2, 138.8, 165.2 (C]O), 165.4 (C]O), 165.9 (C]O).

p-Methylphenyl 2,3,4-tri-O-benzyl-a-L-fucopyranosyl-(1/4)-

2,3,6-tri-O-benzoyl-1-thio-b-^D-glucopyranoside (85)⁴⁴

The product was puried by ash chromatography (PE/EtOAc

5 : 1) on silica gel (230–400 mesh) to give 85 in 88% yield as

colorless syrup. [a]_D²⁷ꢀ10.5 (c 1.2, CHCl₃); lit.⁴⁴[a]²_D⁴ꢀ8.2 (c 0.98,

1

CHCl₃); H (300 MHz, CDCl₃): d 0.59 (d, 3H, J ¼ 6.4 Hz, CH₃),

2.23 (s, 3H, PhCH₃), 3.45 (bs, 1H, H⁰₄), 3.70 (m, 1H, H⁰₅), 3.86–

3.98 (m, 4H, H₄, H₅, H⁰₂, H⁰₃), 4.50 (d, 1H, J ¼ 11.5 Hz, BnH),

4.61–4.86 (m, 8H, 5BnH, H₁, H₆, H⁰₁), 5.06 (d, 1H, J ¼ 10.9 Hz,

H₆), 5.23 (t, 1H, J ¼ 9.7 Hz, H₂), 5.69 (t, 1H, J ¼ 8.9 Hz, H₃), 6.86

(d, 2H, J ¼ 8.0 Hz, ArH), 7.21–7.23 (m, 7H, ArH), 7.25–7.35 (m,

11H, ArH), 7.38–7.44 (m, 4H, ArH), 7.47–7.53 (m, 3H, ArH), 7.62–

7.64 (m, 1H, ArH), 7.83–7.85 (d, 2H, J ¼ 7.4 Hz, ArH), 7.88–7.91

Methyl 3,4,6-tri-O-benzyl-2-deoxy-a-^D-glucopyranosyl-(1/3)-2-

O-benzyl-4,6-O-benzylidene-a-^D-glucopyranoside (90)³²

(d, 2H, J ¼ 7.3 Hz, ArH), 8.06–8.09 (d, 2H, J ¼ 7.3 Hz, ArH). ¹³

C

NMR (75 MHz, CDCl₃): d 15.9, 21.1, 63.1, 67.7, 70.9, 72.7, 74.3,

74.8, 75.6, 75.7, 76.3, 77.2, 77.6, 77.8, 79.2, 85.5 (C₁), 100.5 (C⁰₁),

127.4, 127.5, 127.7, 128.1, 128.2, 128.3, 128.4, 128.41, 129.3,

129.5, 129.8, 129.9, 130.1, 133.0, 133.1, 133.9, 138.1, 138.3,

138.4, 138.6.

The product was puried by ash chromatography (PE/EA 4 : 1)

on silica gel (100–200 mesh) to give 90 in 87% yield as colourless

1

syrup. H (500 MHz, CDCl₃): d 1.60 (dt, 1H, J ¼ 3.5, 12.5 Hz,

H⁰_2a), 2.23 (dd, 1H, J ¼ 4.5, 12.5 Hz, H⁰_2e), 3.29 (s, 3H, OCH₃),

3.36 (dd, 1H, J ¼ 3.5, 9.5 Hz), 3.45–3.49 (m, 2H), 3.54–3.62 (m,

3H), 3.71 (m, 1H), 3.91 (m, 1H), 4.01 (d, 1H, J ¼ 9.5 Hz), 4.14–

4.19 (m, 2H), 4.29 (d, 1H, J ¼ 12.0 Hz, BnH), 4.42 (d, 1H, J ¼

11.0 Hz, BnH), 4.44 (d, 1H, J ¼ 11 Hz, BnH), 4.51–4.60 (m, 5H, 4

ꢃ BnH, H⁰₁), 4.79 (d, 1H, J ¼ 11.0 Hz, BnH), 5.41 (d, 1H, J ¼

4.5 Hz, H1), 5.42 (s, 1H, PhCH) 7.07–7.37 (m, 25H, ArH). ¹³C

NMR (CDCl₃, 75 MHz): d 35.4, 55.3, 61.9, 68.6, 70.7, 71.6, 72.7,

73.4, 73.7, 74.7, 77.4, 78.1, 78.3, 82.9, 97.6, 98.8, 101.4, 126.0,

127.3, 127.4, 127.5, 127.6, 127.7, 127.9, 128.1, 128.15, 128.2,

128.3, 128.4, 128.6, 129.0, 129.8, 134.5, 137.3, 137.7, 138.3,

138.9, 139.1.

Preparation of trisaccharide 2,3,4.6-tetra-O-benzyl-b-^D-

glucopyranosyl-(1/6)-2,3,4-tri-O-benzoyl-b-^D-glucopyranosyl-

(1/6)-1,2:3,4-di-O-isopropylidene-a-^D-galactopyranose (39)^19c

Via sequential one-pot glycosylation technique. A 25 mL

oven-dried round bottom ask was charged with 2,3,4,6-tetra-O-

benzyl-^D-glucopyranosyl trichloroacetimidate donor 1 (155 mg,

0.227 mmol, 1.2 equiv.), 4⁰-methyl phenyl 2,3,4-tri-O-benzoyl-1-

thio-a-^D-glucopyranoside 86 (100 mg, 0.189 mmol, 1 equiv.), and

CH₂Cl₂(5 mL). The resulting solution was stirred on freshly

˚

dried 4 A molecular sieves for 40 min at room temperature

under argon atmosphere. Then this mixture was cooled to

ꢀ60 ^ꢁC, FeCl₃(3.4 mg, 0.024 mmol, 0.1 equiv.) was added, and

the reaction mass was allowed to achieve room temperature.

Aer the acceptor was consumed completely (checked by TLC),

to the reaction mass 1,2:3,4-diisopropyl-a-^D-galactopyranoside 8

(40 mg, 0.151 mmol, 0.8 equiv.) was injected and was cooled on

ice bath NIS (45 mg, 0.227 mmol, 1 equiv.) and FeCl₃(4 mg,

0.024 mmol, 0.1 equiv.) was added one by one. Aer 15 min TLC

was checked and the acceptor was consumed completely. Then

molecular sieves were ltered oﬀ through celite bed. The ltrate

was diluted with CH₂Cl₂and washed subsequently with satu-

rated NaHCO₃solution and water. The organic layer was dried

over anhydrous Na₂SO₄and concentrated to aﬀord the glyco-

sylated product. The crude residue was puried by silica gel

ash column chromatography (hexane/EtOAc, 3 : 1) to aﬀord 39

(196 mg, 87.3%) as a white foam. Spectroscopic data match with

previous one and reported one.

Acknowledgements

Financial support from DST-SERB (Scheme No. SR/S1/OC-61/

2012), New Delhi, India to RG, from CAS-UGC and FIST-DST,

India, to the Department of Chemistry, Jadavpur University

are acknowledged. MMM (SRF) is grateful to UGC, India for

fellowship.

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Article Doi

Iron(iii) chloride modulated selective 1,2-trans glycosylation based on glycosyl trichloroacetimidate donors and its application in orthogonal glycosylation

DOI: 10.1039/c6ra21859h

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