Stereoselective preparation of four 3-C-mannosylated D- and L-glucals from a single starting compound

DOI: 10.1016/j.tet.2011.04.044

Source and publish data:

Tetrahedron p. 4967 - 4979 (2011)

Update date:2022-08-02

Topics:

Authors:

L?vyova, Zuzana

Parkan, Kamil

Knie?o, Ladislav

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Article abstract of DOI:10.1016/j.tet.2011.04.044

The corresponding oxadiene, prepared from the starting perbenzylated α-d-mannopyranosylethanal was subjected to stereoselective cycloaddition reactions with R and S methyl (ethenyloxy)(phenyl)acetates. From the two obtained diastereoisomeric cycloadducts,

Full text of DOI:10.1016/j.tet.2011.04.044

Tetrahedron 67 (20 1 1 ) 4967e4979

Contents lists available at ScienceDirect

Tetrahedron

journal homepage: w ww.elsevier.com/locate/tet

Stereoselective preparation of four 3-C-mannosylated

- and -glucals from

a single starting compound

€

ꢀ

Zuzana Lovyova, Kamil Parkan, Ladislav Kniezo

ꢁ

Department of Chemistry of Natural Compounds, Institute of Chemical Technology, Technicka 5, 166 28 Prague 6, Czech Republic

a r t i c l e i n f o

a b s t r a c t

Article history:

The corresponding oxadiene, prepared from the starting perbenzylated

subjected to stereoselective cycloaddition reactions with R and S methyl (ethenyloxy)(phenyl)acetates.

From the two obtained diastereoisomeric cycloadducts, 3-C- -mannosylated 1,2- -glucal and 3-C-

mannosylated 1,2- -glucal were prepared. A simple epimerisation of the starting -mannopyr-

anosylethanal afforded perbenzylated -mannopyranosylethanal, which was converted to 3-C-

mannosylated 1,2- -glucal or to 3-C- -mannosylated 1,2- -glucal by the same procedure. The structure of

the obtained 3-C- -mannosylated 1,2- -glucal has been conﬁrmed independently by its transformation

tothe knownperacetylated methyl -C-(1/3)-mannobioside. The prepared glucals are suitable precursors

a-D-mannopyranosylethanal was

Received 14 February 2011

Received in revised form 29 March 2011

Accepted 12 April 2011

a-D-

a-D

Available online 20 April 2011

b-D-

-D

Keywords:

C-Disaccharides

Glucal derivatives

Stereoselective synthesis

for the synthesis of stable glycoconjugates with non-hydrolyzable mannose-containing epitopes.

1. Introduction

structure of natural saccharide epitopes but are by far more stable in

the organism because of their resistance to the ubiquitous glycosi-

Communication systems used on a molecular level by living or-

ganisms, are not limited to only the four letters of the genetic al-

phabet. A detailed study of the role played by saccharides in living

organisms revealed that in addition to the two well-known ‘alpha-

bet’ types (represented by amino acids and nucleotides), another

‘alphabet’ type that is utilized in biological recognition processes

may also be formed by monosaccharides.¹Using this alphabet, the

cell surface carbohydrates mediate interactions between them-

selves and other cells (including immunodifferentiation, cell adhe-

sion, cell differentiation, and regulation of cell growth) as well as

between cells and antibodies, viruses, bacteria, peptide hormones or

toxins. Among these interactions, mannose-containing ligands oc-

cupy a signiﬁcant position because theyare present on the surface of

a large number of pathogens, such as viruses (including HIV), bac-

teria, fungi, and parasites. Aside from other lectins, they are also

recognized by the carbohydrate recognition domain of lectin

DC-SIGN, principally expressed by dendritic cells in genital and in-

testinal mucosa.²It has been shown that the inhibition of the rec-

ognition process between the mannose-containing ligands present,

e.g., in HIV glycoprotein gp 120 and lectin DC-SIGN, may inhibit an

infection process at one of the earliest stages.³In the studies of these

and similar processes, it could be useful to obtain C-glycoside or

C-oligosaccharide analogs of saccharides, which can mimic the

dases. The quest for effective synthetic methods leading to glyco-

conjugates with non-hydrolyzable saccharide mimetics is therefore

very desirable. For the synthesis of the glycoconjugates mentioned,

one might advantageously utilize the reactivity of the C]C bond in

1,2-glucals⁴because of its reactivity, which enables one- or two-step

stereoselective preparations of gluco-⁵or mannopyranosyl glyco-

sides,⁶glycosides of glucosamine⁷or mannosamine,⁸and some

C-glycosides.⁹One can envisage that these or similar reactions of

C-mannosylated 1,2-glucals may also be utilized for their attach-

ment to an oligosaccharide, peptide or lipid moieties, either by

glycosidic or CeC bonding, thus enabling the synthesis of various

stable glycoconjugates with non-hydrolyzable mannose-containing

epitopes. Therefore, we decided to prepare diastereoisomeric 3-C-

mannosylated1,2-glucals 1e4 asprecursors for thesynthesis ofnon-

hydrolyzable glycoconjugates, using an approach to the preparation

of 3-C-glycosylated D- and L-1,2-glucals that was recently published

by our group.¹⁰

Thus, in the present paper, we describe a method enabling the

conversion of the starting perbenzylated -mannopyranosyl-

ethanal 5 into either of the two 3-C- -mannosylated 1,2-glucals,

namely 1,5-anhydro-4,6-di-O-benzyl-2,3-dideoxy-3-C-[(2,3,4,6-tetra-

O-benzyl- -mannopyranosyl)methyl]- -arabino-hex-1-enitol

or 1,5-anhydro-4,6-di-O-benzyl-2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-

benzyl- -mannopyranosyl)methyl]- -arabino-hex-1-enitol 2.

Following facile epimerization of aldehyde 5 to -mannopyr-

anosylethanal 6, it is possible to obtain any of the two 3-C-

-mannosylated 1,2-glucals by the same procedure, namely

a-D

b-D

* Corresponding author. Tel.: þ420 220 444 265; fax: þ420 220 444 422; e-mail

b-D

ꢀ

address: Ladislav.Kniezo@vscht.cz (L. Kniezo).

doi:10.1016/j.tet.2011.04.044

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Z. Lovyova et al. / Tetrahedron 67 (2011) 4967e4979

4968

1,5-anhydro-4,6-di-O-benzyl-2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-

benzyl- -mannopyranosyl)methyl]- -arabino-hex-1-enitol 3 and

1,5-anhydro-4,6-di-O-benzyl-2,3-dideoxy-3-C3,4,6-tetra-O-[(2,-

benzyl- -mannopyranosyl)methyl]- -arabino-hex-1-enitol 4.

mixture of peracetylated a- and b-D

-mannopyranosylpropenes.¹⁴Al-

though this mixture is not separable by simple column chromatog-

raphy, our preliminary experiments have shown that replacement of

the acetyl protecting groups by benzyl groups and subsequent ozo-

The structure of the obtained glucal 1 has been conﬁrmed in-

nolysis of the C]C bond leads to a mixture of perbenzylated

a- and b-

dependently by its transformation to the known peracetylated

-mannopyranosylethanals 5 and 6 that are separable (as shown by

methyl

-C-mannobioside 7.¹¹By the same manner, glucal 2 was

TLC) by chromatography on silica gel.

converted to the diastereomeric C-disaccharide 8 with

nopyranose at the reducing end (Scheme 1).

L-man-

We prepared the mixture of peracetylated a- and b-D-mannopyr-

anosylpropenes using a slight modiﬁcationoftheoriginalprocedure.¹⁴

AcO

OAc

AcO

OAc

AcO

OAc

AcO

OAc

AcO

OMe

BnO

OBn

BnO

OBn

BnO

OBn

BnO

CHO

BnO

OBn

BnO

CHO

BnO

Scheme 1. Synthetic route to 3-C-mannosylated glucals 1e4.

2. Results and discussion

A solution of peracetylated D-mannose, 4 equiv of allyltrimethylsilane,

and5.5equivofBF₃$Et₂Owasreﬂuxedinacetonitrilefor5h. Following

The starting perbenzylated

-mannopyranosylethanal 5 is

a workup of the reaction mixture, an unseparable mixture of per-

a known compound,¹²and the best method of its preparation is ozo-

acetylated

yield. Replacement of the acetyl protecting groups by benzyl groups

and the subsequentozonolysis gavea mixture of perbenzylated - and

-mannopyranosylethanals 5 and 6 in the ratio of 9:1 (as de-

termined by integration of the eCHO protons in the ¹H NMR spec-

trum; anomer: triplet at 9.71 ppm, anomer: triplet at 9.56 ppm).

Chromatography of this mixture on silica gel afforded pure perben-

zylated -mannopyranosylethanal 5 in good yield, which in the

a- and b-D-mannopyranosylpropenes was afforded in 75%

nolysis or dihydroxylation of the C]C bond (and its subsequent oxi-

dative cleavage) of perbenzylated

accessible by stereoselective allylation of the

ion generated from suitable precursors.¹³Because we required

greater amount (more than 10 g) of pure -mannopyr-

anosylethanal 5 and its -isomer 6, stereoselective synthesis of mul-

tigram amounts of pure perbenzylated -mannopyranosylpropene

a-D-mannopyranosylpropene,

D-mannopyranosyl cat-

b-D

a-D

did not appear to be practical. Therefore, we tried to obtain the alde-

hyde 5throughamoreeconomicapproach, fromthereadilyaccessible

Wittig reaction with ((2-thiazolylcarbonyl)methylen)triphenylphos-

phorane 9¹⁵gave the only product substituted oxadiene 10, which is

Ph₃P

BnO

OBn

BnO

OBn

BnO

OBn

BnO

iii

BnO

CHO

ratio 5:6 = 9:1

CHO

BnO

OBn

BnO

OBn

BnO

iii

BnO

CHO

ratio 5:6 = 1:9

ratio 10:11 = 1:9

Scheme 2. Synthesis of 10 and 11. Reagents and conditions: (i) 1% K₂CO₃/MeOH, rt, sonication, 6 h; (ii) 9, CHCl₃, 50 ^ꢀC, 48 h; (iii) ﬂash chromatography.

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Z. Lovyova et al. / Tetrahedron 67 (2011) 4967e4979

4969

6´

BnO

the intermediate for the synthesis of glucal 1 or 2 (Scheme 2). It is

evident that, alternatively, the described processes¹³may be used for

the preparation of pure perbenzylated -mannopyranosylpropene,

which can be converted to aldehyde 5 by ozonolysis and subsequently

converted to oxadiene 10 by reaction with phosphorane 9.

OBn

COOCH₃

4´

5´

BnO

1´

2´

3´

COOCH₃

(S)-12

1´´

To synthesize the substituted oxadiene 11, which is an in-

termediate for the synthesis of glucals 3 and 4, we made use of the

BnO

OBn

epimerization of

-D

-mannopyranosylethanal 5. This epimerization

BnO

COOCH₃

was described to proceed in methanolic solution with either

MeONa¹⁶or proline in a microwave oven.¹⁷In the ﬁrst case, how-

COOCH₃

ever, the arising b-D-mannopyranosylethanal 6 was not isolated but

(R)-12

was reduced in situ to the corresponding alcohol. In the second

case, the reaction was performed with only 0.4 mmol of aldehyde 5.

For epimerization of multigram amounts of the aldehyde 5, a 1%

methanolic solution of K₂CO₃proved to be useful. After adding

smaller amounts (ꢁ0.5 g) of pure aldehyde 5 into a stirred solution

of 1% methanolic K₂CO₃at room temperature, equilibrium was

achieved after about 2 days, and according to the ¹H NMR, the

equilibrium mixture consisted of aldehydes 5 and 6 in the ratio of

1:12. Epimerization of greater amounts of the aldehyde was slower,

and moreover, signals of other products began to appear in the

¹H NMR spectrum. However, the epimerization can be markedly

accelerated by sonication. Thus, when 7 g of the starting aldehyde

(or a mixture of aldehydes 5:6¼9:1) was sonicated for 6 h at room

temperature, the equilibrium mixture contained solely compounds

5 and 6 in the ratio of 1:9, whereas after longer periods of sonica-

tion, traces of the side product began to appear. Attempts to sep-

COOCH₃

BnO

OBn

(S)-12

COOCH₃

BnO

OBn

COOCH₃

BnO

(R)-12

COOCH₃

arate

starting

gel were not very successful, and we isolated the pure

a-D

-mannopyranosylethanal 6 from the remnants of the

-mannopyranosylethanal 5 by chromatography on silica

-man-

Scheme 3. Stereoselective synthesis of 13e16. Reagents and conditions: (i) (R)-12 or

(S)-12, Eu(fod)₃(15 mol %), CH₂Cl₂, rt, sonication 48 h; (ii) (R)-12 or (S)-12, Eu(fod)₃

(15 mol %), CH₂Cl₂, rt, sonication 24 h.

b-D

nopyranosylethanal 6 in a maximum yield of about 35%. The low

yield is most likely due to relatively rapid decomposition of 6

(unlike 5) on silica gel. Therefore, we abandoned puriﬁcation at-

tempts at this step and directly subjected the mixture of aldehydes

5 and 6 (1:9) to the Wittig reaction with ((2-thiazolylcarbonyl)-

disaccharides were treated with thiophenol to give anomeric

mixtures of thioglycosides 29a,be32a,b. Hydrolysis of the thio-

glycosides and subsequent mesylation and elimination of the

formed hydroxy group led to glucals 1e4. It is worth mentioning

methylen)triphenylphosphorane 9. The minor a-epimer 10 in the

obtained mixture of oxadienes 10 and 11 was then removed by

chromatography on silica gel, affording pure intermediate 11 in

a good yield.

The obtained intermediates 10 and 11 were subjected to cyclo-

addition reactions with both enantiomers of methyl (ethenylox-

y)(phenyl)acetate, (R)-12 and (S)-12, easily obtainable from cheap

and commercially accessible enantiomers of mandelic acid.¹⁸The

cycloadditions were accelerated by sonication and proceeded at

room temperature in the presence of 0.15 equiv of Eu(fod)₃.The

that in the synthesized structures with the

-mannopyranosyl

moiety (e.g., 13, 14, 25, 26, and 2), this non-reducing

-man-

nohexopyranose showed deviation from the normal ⁴C₁confor-

mation, as follows from lower values (6.4e7.3 Hz) of vicinal diaxial

interactions between H-3⁰and H-4⁰and between H-4⁰and H-5⁰in

the NMR spectra of these compounds. The same effect was also

observed for

steric congestion between the two monosaccharide moieties. In

structures containing the -mannopyranosyl moiety (15, 16, 19,

20, 23, 24, 27, 28, 31a, 3, and 4), this steric congestion is evidently

-C-(1/3)-mannobioside¹¹and was explained by the

b-D

reaction time was 48 h for the

a-D-mannopyranosyl derivative 10

and 24 h for the -mannopyranosyl derivative 11. NOE experi-

not present because their b-D-mannohexopyranose moieties have

ments conﬁrmed the cis-relation of substituents on the C-2 and C-4

atoms of the 3,4-dihydro-2H-pyran ring in all of the obtained

cycloadducts 13e16. On the basis of analogy with similar cycload-

ditions that we had studied earlier,^10,18b,19we can assume with

great certainty that, similar to all preceding cases, the vinyl ether

(S)-12 afforded cycloadducts 13 and 15 with 2R,4R-conﬁguration

and the vinyl ether (R)-12 gave cycloadducts 14 and 16 with 2S,4S-

conﬁguration on the 3,4-dihydro-2H-pyran ring (Scheme 3).

All four synthesized cycloadducts 13e16 were converted into

the ﬁnal glucal derivatives 1e4 using a procedure that was recently

published by our group,¹⁰shown in Scheme 4. Reduction of the

ester group in 13e16, followed by benzylation of the resultant

hydroxy group, afforded compounds 17e20, which gave aldehydes

21e24 after transformation of the thiazole ring. Simultaneous re-

duction of the aldehyde group and hydroboration of the double

bond by BH₃$Me₂S led to C-(1/3)-disaccharides 25e28, having 2-

deoxy-arabino-hexopyranose (compound 25: J_3,49.5 Hz, J_4,59.7 Hz,

compound 26: J_3,4¼J_4,59.7 Hz, compound 27: J_3,4¼J_4,59.7 Hz, and

compound 28: J_3,4¼J_4,59.4 Hz) at the reducing end, and these

‘normal’ values of vicinal diaxial interactions between H-3⁰and

H-4⁰and between H-4⁰and H-5⁰(in the range 9.2e9.7 Hz).

Because the assignment of the D- or L-conﬁguration in glucals

1e4 is based only on analogy with similar previously studied

cycloadditions,^10,18b,19we decided to conﬁrm the assignment un-

equivocally by transforming glucal 1 to the known peracetyl methyl

a-C-(1/3)-mannobioside 7 that has already been prepared by

coupling two D-mannohexopyranoses in an Sm₂I-promoted C-gly-

cosylation.¹¹The simplest way to transform glucal 1 to methyl

C-mannobioside 7 is to perform an epoxidation with m-chlor-

operoxybenzoic acid in methanol, where formation of the

oxide should give rise to the corresponding methyl

glucopyranoside derivative, whereas epoxidation from the -face of

a-ep-

the double bond should lead to the desired methyl mannopyr-

anoside 7. As indicated by the literature data, the diaster-

eoselectivity of this epoxidation may depend signiﬁcantly on the

structure and substitution of the starting unsaturated sacch-

aride. Thus, for example, epoxidation of 4-O-glycosylated glucal,

namely hexa-O-methylmaltal, with m-chloroperoxybenzoic acid in

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Z. Lovyova et al. / Tetrahedron 67 (2011) 4967e4979

4970

OBn

17, R = tetra-O-benzyl-α-D-mannopyranosyl

19, R = tetra-O-benzyl-β−D-mannopyranosyl

18, R = tetra-O-benzyl-α-D-mannopyranosyl

20, R = tetra-O-benzyl-β-D-mannopyranosyl

OBn

21, R = tetra-O-benzyl-α-D-mannopyranosyl

23, R = tetra-O-benzyl-β-D-mannopyranosyl

22, R = tetra-O-benzyl-α-D-mannopyranosyl

24, R = tetra-O-benzyl-β-D-mannopyranosyl

iii

1´´

OBn

1´´

BnO

25, R = tetra-O-benzyl-α-D-mannopyranosyl

27, R = tetra-O-benzyl-β−D-mannopyranosyl

26, R = tetra-O-benzyl-α-D-mannopyranosyl

28, R = tetra-O-benzyl-β−D-mannopyranosyl

OBn

BnO

SPh

BnO

SPh

29a,b, R = tetra-O-benzyl-α-D-mannopyranosyl

31a,b, R = tetra-O-benzyl-β−D-mannopyranosyl

30a,b, R = tetra-O-benzyl-α-D-mannopyranosyl

32a,b, R = tetra-O-benzyl-β-D-mannopyranosyl

Scheme 4. Synthesis of glucals 1e4. Reagents and conditions. (i) (a) LiAlH₄, THF, rt, 1 h; (b) NaH, BnBr, Bu₄NI, THF, 40 ^ꢀC, 4 h, then rt 14 h; (ii) (a) MeOTf, MeCN, rt, 15 min; (b) NaBH₄,

MeOH, rt, 15 min; (c) AgNO₃, MeCN/H₂O, rt, 20 min; (iii) (a) Me₂S$BH₃, THF, rt, 16 h; (b) NaOH, H₂O₂, rt, 30 min; (c) NaH, BnBr, Bu₄NI, THF, 40 ^ꢀC, 4 h, then rt 14 h; (iv) PhSH,

BF₃$Et₂O, CH₂Cl₂, ꢂ78 ^ꢀC, then to rt 2 h; (v) (a) NBS, moist acetone (1% H₂O), ꢂ15 ^ꢀC, 1 h, exclusion of light; (b) Ms₂O, s-collidine, CH₂Cl₂, 0 ^ꢀC, 4 h.

methanol proceeded selectively from the

methyl hexa-O-methyl-

-maltoside.²⁰The same epoxidation of

3-C-glycosylated galactal, i.e., 4,6-di-O-benzyl-3-C-[(1R)-1,3,4,5,

7-penta-O-benzyl-2,6-anhydro- -glycero- -manno-heptitol-1-C-yl]-

3-deoxy- -galactal, took place predominantly from the -face under

formation of methyl 4,6-di-O-benzyl-1,3-C-[(1R)-1,3,4,5,7-penta-O-

benzyl-2,6-anhydro- -glycero- -manno-heptitol-1-C-yl]-3-deoxy-

-talo-pyranoside as the principal reaction product.²¹

We performed this simple epoxidation with glucal 1 and found

that the reaction also proceeded preferentially from the -face and

that stereoselectivity of the epoxidation is practically the same as in

the case of the C-glycosylated galactal.²¹The epoxidation afforded

a mixture of two methyl glycosides 33 and 34, which were easily

separable by chromatography on silica gel (Scheme 5). The major

product 33 was isolated chromatographically in 56% yield, and the

minor product 34 was isolated in 20% yield. Both products had the

same molecular weight (MS), corresponding to the expected

methyl glycosides. In the ¹H NMR spectrum of 33, the H-1 proton

appeared as a broad singlet at 4.29 ppm, which corresponds to the

-face, affording solely

methyl

34, the H-1 proton appeared as a doublet at 4.13 ppm (J_1,27.6 Hz),

corresponding to methyl -glucopyranoside. Moreover, debenzy-

a-mannopyranoside structure, whereas in the spectrum of

lation, followed by acetylation of the major product 33, afforded

a compound whose NMR spectra were identical with those pub-

lished for peracetylated methyl a

-C-(1/3)-mannobioside 7.¹¹The

only signiﬁcant difference was the chemical shift of the methylene

protons of the C-glycoside bond (H-1⁰⁰a,b), described in the original

paper as a multiplet at 1.40 to 1.24 ppm, which we found to be

a multiplet at 1.88 to 1.83 ppm, partly overlapped with signals of

acetyl groups. Chemical shifts of these protons were conﬁrmed by

using COSY and HMQC spectra. Because the chemical shifts and

multiplicities of other protons were identical with the published

values, we assume that the chemical shift of the C-glycoside

methylene protons was assigned erroneously in the original paper.

By analogy, the same epoxidation of glucal 2 afforded a mixture

of two methyl glycosides 35 and 36, which were isolated by chro-

matography on silica gel in the yields of 51% and 20%, respectively.

Similar to the preceding case, the H-1 proton in the major methyl

a-D

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Z. Lovyova et al. / Tetrahedron 67 (2011) 4967e4979

4971

BnO

OBn

BnO

OBn

BnO

OBn

BnO

OBn

BnO

OBn

BnO

OMe

BnO

OMe

BnO

OBn

BnO

OBn

BnO

OMe

BnO

OMe

Scheme 5. Epoxidation of glucals 1 and 2. Reagents and conditions: (i) MCPBA, MeOH, CH₂Cl₂, rt, 1.5 h.

glycoside 35 exhibited a broad singlet at 4.59 ppm, whereas in the

methyl glycoside 36, it appeared as a doublet at 4.11 ppm (J_1,2

7.6 Hz). Debenzylation of methyl glycoside 35 followed by acety-

lation afforded C-disaccharide 8, whose ¹H NMR spectrum was

similar to that of compound 7. However, it exhibited signiﬁcant

differences in chemical shifts or coupling constants for some pro-

tons. The most signiﬁcant chemical shift differences (more than

0.1 ppm) were found for the protons H-1, H-2, H-3, and H-4 and for

the methylene protons of the C-glycoside bond, which appeared as

two discrete multiplets at 1.92 and 1.77 ppm. In regard to the

coupling constants, the most signiﬁcant deviations were observed

for the H-3 proton.

and the subsequent facile chromatographic isolation of C-di-

saccharide 33 represent a good alternative to the published prepa-

ration of this structure.¹¹Moreover, the prepared 3-C-mannosylated

1,2-glucals 1e4 are useful intermediates for preparation of various

non-hydrolyzable mannosedcontaining (1/3)-disaccharide mi-

metics, which may serve either as tools for study of recognition

processes with lectins or for synthesis of non-hydrolyzable glyco-

protein or glycolipid epitopes.

4. Experimental

4.1. General methods

Comparison of the NMR spectra of the obtained methyl glyco-

sides 7 and 8 with the published spectra of methyl

mannobioside showed convincing evidence that compound 7 is

identical to the known methyl -C-(1/3)-mannobioside, whereas

a-C-(1/3)-

All solvents were puriﬁed by standard procedures. TLC was

performed on HF₂₅₄plates (Merck), and the detection utilized ei-

ther UV light or spraying with Ce(SO₄)₂solution (5 g) in 10% H₂SO₄

(500 mL), with subsequent heating. Flash column chromatography

compound 8 is its diastereoisomer. The differences in the H-3

proton coupling constants (for 7: J 11.0, 5.5, 5.5, 3.0 Hz, and for 8: J

11.2, 11.2, 3.1, 3.1 Hz) agree with the fact that C-disaccharides 7 and

8 differ in the absolute conﬁguration of mannohexopyranose at the

reducing end, which manifests itself in different conformational

preferences of the C-aglycone bond. Thus, as follows from the

obtained NMR spectra, the conﬁguration for the cycloadducts 13

and 14 have been assigned correctly and compounds 1 and 3 are 3-

was performed on silica gel (Merck, 100e160 mm) with solvents

that had been distilled prior to use. Optical rotations were mea-

sured at 20 ^ꢀC on a spectropolarimeter Autopol VI. ¹H (300 and

500 MHz) and ¹³C (75 and 125.7 MHz) NMR spectra were recorded

on Varian Oxford 300 and Bruker DRX 500 Avance spectrometers,

using tetramethylsilane as an internal standard. The assignments of

¹H and ¹³C signals were conﬁrmed by homonuclear COSY and

heteronuclear 2D correlated spectra, respectively. NOE connectiv-

ities were obtained using 1D ¹H DPFGSE-NOE experiments. Infrared

spectra were recorded as CHCl₃solutions on Nicolet 750 FT-IR

spectrometer and are reported in wave numbers (cm^ꢂ1). Mass

spectra and HPLC were performed on a 250ꢃ4.6 mm column

C-mannosylated glucals with D-conﬁguration, whereas compounds

2 and 4 are 3-C-mannosylated glucals with L-conﬁguration.

3. Conclusion

In summary, we have reported a stereoselective synthesis of any

of the four diastereoisomeric 3-C-mannosylated 1,2-glucals (1,5-

anhydro-2,3-dideoxy-arabino-hex-1-enitols) 1e4 starting from the

packed with 5 mm Supelco BDS Hypersil C-18, with a mobile phase

of MeOH/water, using an HP 1100 instrument equipped with

a gradient pump, a column thermostat and, in addition to a UV

detector, an Agilent G1956B single quadrupole system as an MS

detector.

known a-D-mannopyranosylethanal 5. The key step of the synthetic

protocol is the cycloaddition of substituted oxadienes, prepared

from starting aldehyde 5, with chiral vinyl ethers derived from both

enantiomers of mandelic acid. The ﬁnal compounds were obtained

in seven steps with overall yields 8.37% (for 1), 9.17% (for 2), 9.37%

(for 3), and 9.00% (for 4). Epoxidation of glucals 1 or 2 in methanol

afforded as the principal reaction products methyl glycosides of

C-disaccharides 33 or 35 in 56% and 51% isolated yields, respectively.

The obtained methyl glycoside 33 is a non-hydrolyzable analog of

4.1.1. (2,3,4,6-Tetra-O-benzyl-a-D-mannopyranosyl)-ethanal

(5). Allyltrimethylsilane (60 mL, 368 mmol) and BF₃$Et₂O (65 mL,

492 mmol) were portionwise added to a solution of 1,2,3,4,6-penta-

O-acetyl-D-mannopyranose (35 g, 93 mmol) in dry CH₃CN (500 mL).

The mixture was reﬂuxed for 5 h, then cooled to room temperature,

and after concentration diluted with CH₂Cl₂(500 mL). The solution

was washed with 2 M NaOH under vigorous stirring to persisting

alkaline reaction of the aqueous phase. The organic layer was

washed with NaHCO₃solution, dried over MgSO₄, and the solvent

disaccharide a-D-Man-(1/3)-D-Man, which is signiﬁcantly present

in cell surface carbohydrates as the core branching region of aspar-

agine-linked oligosaccharides. The simple epoxidation of glucal 1

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Z. Lovyova et al. / Tetrahedron 67 (2011) 4967e4979

4972

was evaporated. Chromatography of the residue (light petroleum/

ethyl acetate, 3:1) afforded an unseparable mixture of and

-mannopyranosyl)-prop-2-enes (25 g,

H-2, H-3), 4.64e4.44 (m, 8H, 4ꢃ OeCH₂ePh), 4.16 (m, 1H, H-1⁰),

3.96 (dd,1H, J_{4 ,5}10.4 Hz, J_{5 ,6 b}5.0 Hz, H-5⁰), 3.91e3.76 (m, 3H, H-3⁰,

0 0 0 0

(2,3,4,6-tetra-O-acetyl-

H-6⁰a, H-4⁰), 3.72 (dd, 1H, J_{6 a,6 b}10.3 Hz, J_{6 b,5}5.0 Hz, H-6⁰b), 3.62

0 0 0 0

75%); R_f¼0.5 (light petroleum/ethyl acetate, 2:1). ESIMS: MH^þ

found: 373.7. C₁₇H₂₅O₉requires 373.2. The spectroscopic data were

consistent with those reported.¹⁴A 0.1 M solution of MeONa in

MeOH was added dropwise to the obtained mixture of peracetylated

(dd,1H, J_{3 ,2}6.3 Hz, J_{2 ,1}2.7 Hz, H-2⁰), 2.73e2.52 (m, 2H, H-4a, H-

4b); ¹³C NMR (125 MHz, CDCl₃) 180.9 (C-1), 167.8 (thiazol C-2),

146.7 (C-2), 144.4 (CeH thiazol), 138.1, 137.9, 137.7, 137.6 (4ꢃ ipso

C₆H₅), 128.2e127.2 (20ꢃ C₆H₅), 126.3 (C-3), 126.0 (CeH thiazol),

75.4 (C-2⁰), 75.1, 74.3 (C-3⁰, C-4⁰), 73.9 (C-5⁰), 72.9, 72.7, 72.0, 71_þ.2

(4ꢃ CH₂ePh), 70.3 (C-5⁰), 68.4 (C-6⁰), 34.1 (C-4). ESIMS: MH ,

found: 676.4. C₄₁H₄₂NO₆S requires 676.8.

D-mannopyranosylprop-2-enes in MeOH (500 mL) to allow the al-

kaline reaction to persist, and the reaction mixture was stirred at

room temperature. After 20 h, no starting compound was detected

(TLC) in the reaction mixture, and the reaction was then neutralized

with Dowex 50 (5 g) and ﬁltered. Evaporation of the solvent and

chromatography on silica gel (chloroform/MeOH, 5:1) afforded 13 g

4.1.3. (E)-4-(2,3,4,6-Tetra-O-benzyl-b-D-mannopyranosyl)-1-(thia-

zol-2-yl)-but-2-en-1-one (11). Aldehyde 5 (or the mixture of alde-

hydes 5 and 6 in a ratio of 9:1) (7.0 g, 12.3 mmol) was dissolved in

a 1% methanolic solution of K₂CO₃(270 mL) and was sonicated at

room temperature. According to ¹H NMR, the reaction mixture

contained the mixture of aldehydes 5 and 6 in a ratio of 1:9 after

6 h. The reaction was quenched by neutralization with acetic acid,

the solvent was evaporated, and the residue was partitioned be-

tween CH₂Cl₂and a saturated NaCl solution. The organic phase was

dried, the solvent evaporated, and the residue dissolved in CHCl₃.

Ylide 9¹⁵(10.5 g, 27.2 mmol) was added to the solution, and the

mixture was heated at 50 ^ꢀC. After 30 h, the reaction mixture did

not show any aldehyde proton signals in the ¹H NMR spectrum. The

solvent was evaporated, and the residue was chromatographed on

silica gel (light petroleum/ethyl acetate, 5:1/3:1), affording 3.8 g

(60%) of compound 11 as a yellow viscous oil; [Found: C, 72.64; H,

of a mixture of

(chloroform/MeOH, 5:1). ESIMS: MH^þfound: 205.7. C₉H₁₇O₅re-

quires 205.2. The obtained mixture of -mannopyranosylprop-2-

and

-mannopyranosylprop-2-enes; R_f¼0.4

enes was dissolved in dry tetrahydrofuran (400 mL). To this solution,

we added 11.8 g (296.7 mmol) of a 60% suspension of NaH in mineral

oil, and the reaction mixturewas stirredat room temperature for 1 h.

Then, tetrabutylammonium iodide (4.56 g, 12.3 mmol) was added,

followed by dropwise addition of benzyl bromide (35.3 mL,

296.7 mmol). The reaction mixture was heated at 50 ^ꢀC for 2 h and

then stirred at room temperature for another 15 h. The excess hy-

dride was decomposed by the addition of MeOH (5 mL), the solvent

was evaporated, and the residue was partitioned between CH₂Cl₂

and H₂O. The organic phases were combined, dried, and stripped of

solvent, and the residue was chromatographed on silica gel (light

petroleum/ethyl acetate, 12:1/9:1). This procedure yielded 33 g of

6.25. C₄₁H₄₁NO₆S requires C, 72.86; H, 6.11%]; R_f¼0.32 (light pe-

a mixture of

and

perbenzylated

-mannopyranosylprop-2-enes;

troleum/ethyl acetate, 3:1); [

]

þ7.4 (c 0.74, CHCl₃); n_max3009,

R_f¼0.35 (light petroleum/ethyl acetate, 9:1). ESIMS: MH^þfound:

565.8. C₃₇H₄₁O₅requires 565.7. The mixture obtained was dissolved

in dry dichloromethane (200 mL) and was subsequently ozonized,

after addition of anhydrous MeOH (40 mL) and cooling to ꢂ78 ^ꢀC.

After 20 min, the mixture did not contain (TLC) any starting com-

pound, and the reaction was terminated by passing nitrogen

through the mixture for 5 min. Then NaHCO₃(4 g) (to prevent an

acetalization) and then dimethyl sulﬁde (43 mL, 587 mmol) were

added successively, and the stirred mixture was allowed to warm to

room temperature. After stirring the mixture for 3 days at room

temperature, the NaHCO₃was ﬁltered off, and the solvent was

evaporated. ¹H NMR of the crude product showed the presence of

1675, 1627, 1453, 1390, 1095, 1028 cm^ꢂ1; ¹H NMR (500 MHz, CDCl₃)

7.99 (d, 1H, H-thiazol, J 2.9 Hz), 7.65 (d, 1H, H-thiazol, J 2.9 Hz),

7.15e7.42 (m, 22H, 4ꢃ C₆H₅, H-2, H-3), 4.5e5.1 (m, 8H, 4ꢃ

OeCH₂ePh), 3.95 (dd, 1H, J_{4 ,5}10.0 Hz, J_{4 ,H-3}9.5 Hz, H-4 ), 3.77 (m,

2H, H-2⁰, H-6⁰a), 3.70 (dd, 1H, J_{6 a,6 b}10.9 Hz, J_{6 b,5}5.3 Hz, H-6⁰b),

3.64 (dd,1H, J_{3 ,4}9.5 Hz, J_{3 ,2}2.2 Hz, H-3⁰), 3.49 (m, 2H, H-1⁰, H-5⁰),

2.78 (m, 1H, H-4a), 2.49 (m, 1H, H-4b); ¹³C NMR (125 MHz, CDCl₃)

181.4 (C-1), 168.1 (thiazol C-2), 147.0 (C-2), 144.7 (CeH thiazol),

138.4, 138.3, 138.2 (4ꢃ ipso C₆H₅), 128.5e127.4 (20ꢃ C₆H₅), 126.4

(CeH thiazol), 126.3 (C-3), 85.2 (C-3⁰), 79.9, 77.1 (C-1⁰, C-5⁰), 74.9

(C-2⁰, C-4⁰), 74.3, 73.5, 72.6 (4ꢃ CH₂ePh), 69.5 (C-6⁰), 34.9 (C-4).

ESIMS: MNH^þ₄, found, 693.2. C₄₁H₄₂N₂O₆S requires 693.3.

a mixture of

and 6 in a 9:1 ratio (aldehyde proton of the

a triplet at 9.71 ppm and that of the -diastereoisomer as a triplet at

and

perbenzylated

-mannopyranosylethanals 5

-diastereoisomer as

4.1.4. Methyl (S)-2-phenyl-2-{[(2R,4R)-4-(2,3,4,6-tetra-O-benzyl-

D-mannopyranosyl)methyl-6-(thiazol-2-yl)-3,4-dihydro-2H-pyran-2-

9.56 ppm). Chromatography on a silica gel column (light petroleum/

ethyl acetate, 9:1/5:1) afforded 23 g (60% from mixture of per-

yl]oxy}acetate (13). Eu(fod)₃(2.10 g, 2.06 mmol) was added to

a solution of compound 10 (9.0 g, 13.3 mmol) and chiral vinyl ether

(S)-12¹⁸(3.9 g, 20.3 mmol) in dichloromethane (200 mL), and the

reaction mixture was sonicated at room temperature. After 48 h,

the mixture did not contain (TLC) any starting compound 10.

Evaporation of solvent and chromatography of the residue on silica

gel (light petroleum/ethyl acetate, 3:1/2:1) afforded 8.7 g (75%) of

compound 13 as a colorless foam; [Found: C, 71.78; H, 6.05.

C₅₂H₅₃NO₉S requires C, 71.95; H, 6.15%]; R_f¼0.30 (light petroleum/

acetylated

zyl-

-mannopyranosyl)-ethanal 5; R_f¼0.35 (light petroleum/ethyl

acetate, 3:1) and 6.5 g of a mixture of and of perbenzylated

D-mannopyranosylprop-2-enes) of (2,3,4,6-tetra-O-ben-

a-D

D-

mannopyranosylethanals 5 and 6; R_f¼0.30 (light petroleum/ethyl

acetate, 3:1). The spectroscopic data obtained for compound 5 were

identical to those reported.^12b

4.1.2. (E)-4-(2,3,4,6-Tetra-O-benzyl-

-mannopyranosyl)-1-(thia-

ethyl acetate, 2:1); [

]

²⁰þ21.1 (c 1.36, CHCl₃); n_max3010,1736, 1496,

zol-2-yl)-but-2-en-1-one (10). Ylide 9¹⁵(17.2 g, 44.5 mmol) was

added to a solution of aldehyde 5 (11.5 g, 20.3 mmol) in CHCl₃

(130 mL), and the mixture was stirred and heated at 50 ^ꢀC. After

48 h, the reaction mixture did not show an aldehyde proton signal

(9.71 ppm) in the ¹H NMR spectrum. The solvent was evaporated,

and the residue was chromatographed on silica gel (light petro-

leum/ethyl acetate, 5:1/3:1), affording 9.6 g (70%) of compound

10 as a yellow viscous oil; [Found: C, 72.66; H, 5.96. C₄₁H₄₁NO₆S

1454, 1272, 1095, 1028 cm^ꢂ1; ¹H NMR (500 MHz, CDCl₃) 7.73 (d, 1H,

H-thiazol, J 3.2 Hz), 7.45e7.15 (m, 26H, 5ꢃ C₆H₅, H-thiazol), 6.05

(d, INS> 1H, J_5,43.7 Hz, H-5), 5.46 (s, 1H, PhCHCOOCH₃), 5.42 (dd,

1H, J_2,3ax5.5 Hz, J_2,3eq2.2 Hz, H-2), 4.73e4.42 (m, 8H, 4ꢃ

OeCH₂ePh), 4.18 (m,1H, H-1⁰), 3.92e3.81 (m, 3H, H-4⁰, H-5⁰, H-6⁰a),

3.76 (dd, 1H, J_{6 a,6 b}10.5 Hz, J_{6 ,5}3.3 Hz, H-6⁰b), 3.71 (dd, 1H, J_{3 ,4}

6.7 Hz, J_{3 ,2}2.7 Hz, H-3⁰), 3.68 (s, 3H, COOCH₃), 3.49 (dd, 1H, J_{2 ,1}

4.3 Hz, J_{3 ,2}2.7 Hz, H-2⁰), 2.67 (m, 1H, H-4), 2.23 (ddd, 1H, J_3eq,3ax

13.7 Hz, J_3eq,46.8 Hz, J_3eq,22.2 Hz, H-3_eq), 2.04 (ddd, 1H, J_3eq,3ax

13.7 Hz, J_3ax,45.9 Hz, J_3ax,25.5 Hz, H-3_ax), 1.89 (m, 1H, H-1⁰⁰a), 1.70

(m, 1H, H-1⁰⁰b); ¹³C NMR (125 MHz, CDCl₃) 170.8 (COOCH₃), 163.9

(thiazol C-2), 143.1 (CeH thiazol), 143.0 (C-6), 138.4, 138.3, 138.2,

requires C, 72.86; H, 6.11%]; R_f¼0.3 (light petroleum/ethyl acetate,

3:1); [

þ9.5 (c 0.74, CHCl₃); n_max3011, 1671, 1625, 1454, 1390,

1094, 1028 cm^ꢂ1; ¹H NMR (500 MHz, CDCl₃) 7.89 (d, 1H, J 3.0 Hz, H-

thiazol), 7.52 (d,1H, J 3.0 Hz, H-thiazol), 7.15e7.40 (m, 22H, 4ꢃ C₆H₅,

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Z. Lovyova et al. / Tetrahedron 67 (2011) 4967e4979

4973

138.1, 136.1 (5ꢃ ipso C₆H₅), 128.4e127.1 (25ꢃ C₆H₅), 118.5 (CeH

thiazol), 104.6 (C-5), 97.9 (C-2), 77.6 (PhCHCOOCH₃), 77.3 (C-3⁰),

76.6 (C-2⁰), 74.8, 73.4 (C-4⁰, C-5⁰), 73.6, 73.2, 72.0, 71.6 (4ꢃ CH₂ePh),

71.1 (C-1⁰), 69.2 (C-6⁰), 52.2 (COOCH₃), 35.4 (C-1⁰⁰), 32.8 (C-3), 27.1

(C-4). ESIMS: MH^þ, found, 869.3. C₅₂H₅₄NO₉S requires 869.1.

6.5 Hz, J_2,3eq2.0 Hz, H-2), 4.90e4.48 (m, 8H, 4ꢃ OeCH₂ePh), 3.94

(dd, 1H, J_{4 ,5}¼J_{4 ,3}9.3 Hz, H-4⁰), 3.78e3.69 (m, 2H, H-6⁰a, H-6⁰b),

3.68 (s, 3H, COOCH₃), 3.62e3.56 (m, 2H, H-3⁰, H-2), 3.50 (m, 1H, H-

1⁰), 3.45 (m, 1H, H-5⁰), 2.70 (m, 1H, H-4), 2.27 (ddd, 1H, J_3eq,3ax

13.5 Hz, J_3eq,47.1 Hz, J_2,3eq2.0 Hz, H-3_eq), 2.11 (m, 1H, H-1⁰⁰a), 1.88

(ddd, 1H, J_3eq,3ax13.5 Hz, J_3ax,46.9 Hz, J_2,3ax6.5 Hz, H-3_ax), 1.52 (m,

1H, H-1⁰⁰b); ¹³C NMR (125 MHz, CDCl₃) 170.7 (COOCH₃), 163.9

(thiazol C-2), 143.1 (C-6), 143.1 (CeH thiazol), 138.5, 138.4, 138.3,

13.2, 136.0 (5ꢃ ipso C₆H₅), 128.4e127.0 (25ꢃ C₆H₅), 118.5 (CeH

thiazol), 104.2 (C-5), 98.1 (C-2), 85.0 (C-3⁰), 79.6 (C-5⁰), 77.4 (C-2⁰),

76.3 (PhCHCOOCH₃), 75.4 (C-4⁰), 75.3 (C-1⁰), 74.9, 74.4, 73.2, 72.3

(4ꢃ PhCH₂), 69.5 (C-6⁰), 52.2 (COOCH₃), 37.6 (C-1⁰⁰), 33.5 (C-3),

26.42 (C-4). ESIMS: MH^þ, found, 869.2. C₅₂H₅₄NO₉S requires 869.1.

4.1.5. Methyl (R)-2-phenyl-2-{[(2S,4S)-4-(2,3,4,6-tetra-O-benzyl-

D-mannopyranosyl)methyl-6-(thiazol-2-yl)-3,4-dihydro-2H-pyran-2-

yl]oxy}acetate (14). According to the same procedure described for

the preparation of compound 13, compound 10 (8.0 g, 11.8 mmol)

and chiral vinyl ether (R)-12¹⁸(3.4 g, 17.8 mmol) afforded 8.2 g

(80%) of compound 14 as a colorless foam; [Found: C, 71.75; H, 5.95.

C₅₂H₅₃NO₉S requires C, 71.95; H, 6.15%]; R_f¼0.30 (light petroleum/

ethyl acetate, 2:1); [

]

ꢂ9.1 (c 0.99, CHCl₃); n_max3011, 1747,

1496,1454, 1272, 1096, 1028 cm^ꢂ1

;

¹H NMR (500 MHz, CDCl₃) 7.73

4.1.8. (2R,4R)-2-[(S)-2-(Benzyloxy)-1-phenylethoxy]-4-[(2,3,4,6-

(d, 1H, H-thiazol, J 3.2 Hz), 7.45e7.13 (m, 26H, 5ꢃ C₆H₅, H-thiazol),

5.95 (d,1H, J_5,43.9 Hz, H-5), 5.46 (s, 1H, PhCHCOOCH₃), 5.41 (dd, 1H,

J_2,3ax6.0 Hz, J_2,3eq2.3 Hz, H-2), 4.73e4.42 (m, 8H, 4ꢃ OeCH₂ePh),

tetra-O-benzyl-a-D-mannopyranosyl)methyl]-6-(thiazol-2-yl)-3,4-di-

hydro-2H-pyran (17). Lithium aluminum hydride (0.9 g, 23.7 mmol)

was added portionwise under argon to a solution of compound 13

(6.9 g, 7.9 mmol) in tetrahydrofuran (120 mL) that was pre-cooled to

0 ^ꢀC, and the reaction mixture was stirred at room temperature for

1 h. After cautious addition of a 1 M solution of NaOH (10 mL), the

reaction mixture was concentrated and partitioned between a 0.5 M

solution of HCl and CH₂Cl₂. The organic layer was washed with

NaHCO₃solution and dried. The solvent was subsequently evapo-

rated, and the residue was subjected to ﬂash chromatography

through a short column of silica gel in light petroleum/ethyl acetate

(5:1). The obtained alcohol (6.34 g, R_f¼0.4 in light petroleum/ethyl

acetate, 4:1, m/z 839.6 [MþH]^þ) was dissolved in tetrahydrofuran

(300 mL), and the solution was stirred at room temperature for 1 h

with a 60% suspension of NaH in mineral oil (1.9 g, 47.5 mmol). Then,

benzyl bromide (2.7 mL, 18.7 mmol) and tetrabutylammonium io-

dide (0.71 g, 1.9 mmol) were added, and the reaction mixture was

heated at 40 ^ꢀC for 4 h and then stirred at room temperature for 14 h.

MeOH (5 mL) was added, the solvent was evaporated in vacuo, and

the residue was partitioned between dichloromethane and a satu-

rated solution of NaHCO₃. Then, the organic layer was dried, the

solvent was taken down, and the residue was chromatographed on

silica gel in lightpetroleum/ethyl acetate(12:1/3:1). This procedure

yielded 5.2 g (70%) of compound 17 as a pale yellow viscous oil;

4.18 (m, 1H, H-1⁰), 3.86 (dd, 1H, J_{4 ,5}¼J_{4 ,3}6.4 Hz, H-4⁰), 3.82e3.74

(m, 2H, H-3⁰, H, 6⁰a), 3.70 (m,5H, COOCH₃, H-5⁰, H-6⁰b), 3.52 (dd, 1H,

J_{2 ,3}4.8 Hz, J_{2 ,1}3.0 Hz, H-2 ), 2.71 (m,1H, H-4), 2.18 (ddd,1H, J_3eq,3ax

13.6 Hz, J_3eq,46.8 Hz, J_3eq,22.3 Hz, H-3_eq), 1.98e1.79 (m, 2H, H-3, H-

1⁰⁰), 1.63 (m, 1H, H-1⁰⁰); ¹³C NMR (125 MHz, CDCl₃) 170.8 (COOCH₃),

163.9 (thiazol C-2), 143.2, 143.1 (C-6, CeH thiazol), 138.4, 138.2,

138.1, 136.2 (5ꢃ ipso C₆H₅), 128.5e127.1 (25ꢃ C₆H₅), 118.4 (CeH

thiazol), 106.1 (C-5), 98.3 (C-2), 77.7 (PhCHCOOCH₃), 77.1 (C-4⁰),

76.5 (C-2⁰), 74.8 (C-5⁰), 73.6, 73.3, 72.1, 71.6 (4ꢃ PhCH₂), 73.5 (C-3⁰),

70.1 (C-1⁰), 68.9 (C-6⁰), 52.2 (COOCH₃), 35.1 (C-1⁰⁰), 31.5 (C-3), 26.9

(C-4). ESIMS: MH^þ, found, 869.3. C₅₂H₅₄NO₉S requires 869.1.

4.1.6. Methyl (S)-2-phenyl-2-{[(2R,4R)-4-(2,3,4,6-tetra-O-benzyl-

D-mannopyranosyl)methyl-6-(thiazol-2-yl)-3,4-dihydro-2H-pyran-2-

yl]oxy}acetate (15). According to the same procedure described for

the preparation of compound 13 after 24 h of soniﬁcation, com-

pound 11 (9.25 g, 13.69 mmol) and chiral vinyl ether (S)-12 (3.94 g,

20.54 mmol) afforded 9.2 g (77%) of compound 15 as a colorless

foam; [Found: C, 80.05; H, 6.25. C₅₂H₅₃NO₉S requires C, 71.95; H,

6.15%]; R_f¼0.30 (light petroleum/ethyl acetate, 2:1); [

]

þ15.0 (c

1.02, CHCl₃); n_max3015, 1745, 1497, 1456, 1272, 1096, 1028 cm^ꢂ1; ¹H

NMR (300 MHz, CDCl₃) 7.77 (d, 1H, H-thiazol, J 2.6 Hz); 7.48e7.16

(m, 26H, 5ꢃ C₆H₅, H-thiazol), 5.96 (d,1H, J_5,43.5 Hz, H-5), 5.49 (s,

1H, PhCHCOOCH₃), 5.38 (dd, 1H, J_2,3ax6.4 Hz, J_2,3eq2.3 Hz, H-2),

[Found: C, 74.75; H, 6.55. C₅₈H₅₉NO₈S requires C, 74.89; H, 6.39%];

R_f¼0.35 (light petroleum/ethyl acetate, 3:1); [

]

þ12.4 (c 1.43,

CHCl₃);n_max3011,1722,1700,1496,1454,1363,1265,1094,1028cm^ꢂ1

;

4.51e5.15 (m, 8H, 4ꢃ OeCH₂ePh), 3.95 (dd, 1H, J_{4 ,5}10.0 Hz, J_{4 ,3}

¹H NMR (500 MHz, CDCl₃) 7.63 (d, 1H, H-thiazol, J 3.2 Hz), 7.38e7.09

(m, 30H, 6ꢃ C₆H₅), 7.04 (d, 1H, J 3.2 Hz, H-thiazol), 6.01 (d,1H, J_5,4

3.7 Hz, H-5), 5.48 (dd,1H, J_2,3eq2.2 Hz, J_2,3ax5.8 Hz, H-2), 4.94 (dd,1H, J

8.2 Hz, J 3.5 Hz, PhCHCH₂OBn), 4.70e4.47 (m, 10H, 5ꢃ OeCH₂ePh),

9.5 Hz, H-4⁰), 3.77 (m, 2H, H-2⁰, H-6⁰a), 3.75 (s, 3H, COOCH₃), 3.70

(dd, 1H, J_{6 a,6 b}10.9 Hz, J_{6 b,5}5.3 Hz, H-6⁰b), 3.64 (dd,1H, J_{3 ,4}9.5 Hz,

J_{3 ,2}2.2 Hz, H-3⁰), 3.50e3.45 (m, 2H, H-1⁰, H-5⁰), 2.55 (m, 1H, H-4),

2.20e2.15 (m, 2H, H-3_eq, H-1⁰⁰), 1.85 (m, 1H, H-3_ax), 1.57 (m, 1H, H-

1⁰⁰); ¹³C NMR (75 MHz, CDCl₃) 171.2 (COOCH₃), 164.3 (thiazol C-2),

143.6, 143.5 (C-6, CeH thiazol), 138.8, 138.7, 136.4 (5ꢃ ipso C₆H₅),

128.9e127.5 (25ꢃC₆H₅), 118.9 (CeH thiazol), 106.0 (C-5), 98.7 (C-2),

85.7 (C-3⁰), 77.9 (PhCHCOOCH₃), 76.0, 75.8, 75.7 (C-5⁰, C-2⁰, C-1⁰),

75.8 (C-4⁰), 74.7, 73.7, 72.8 (4ꢃ PhCH₂), 70.0 (C-6⁰), 52.7 (COOCH₃),

36.9 (C-1⁰⁰), 32.3 (C-3), 27.1 (C-4). ESIMS: MH^þ, found, 869.2.

C₅₂H₅₄NO₉S requires 869.1.

4.23 (ddd,1H, J_{1 ,1 a}10.5 Hz, J_{1 ,1 b}4.5 Hz, J_{1 ,2}3.0 Hz, H-1 ), 3.95e3.86

(m, 2H,H-4⁰, H-5⁰), 3.85e3.72(m, 3H,H-3⁰, H-6⁰a, H-6⁰b), 3.66(dd,1H,

J 10.6 Hz, J 8.2 Hz, PhCHCH_2aOBn), 3.58 (dd, 1H, J 10.6 Hz, J 3.5 Hz,

PhCHCH_2bOBn), 3.54 (dd, 1H, J_{2 ,3}4.8 Hz, J_{2 ,1}3.0 Hz, H-2 ), 2.66 (m,

1H, H-4), 2.15 (ddd, 1H, J_3eq,3ax13.5 Hz, J_3eq,46.9 Hz, J_2,3eq2.2 Hz, H-

3_eq), 2.00e1.85 (m, 2H, H-1⁰⁰a, H-3_ax), 1.80 (m, 1H, H-1⁰⁰b); ¹³C NMR

(125 MHz, CDCl₃) 164.2 (thiazol C-2),143.5 (C-6),142.6 (CeH thiazol),

139.6, 138.3, 138.2, 138.1, 138.1, 138.0 (6ꢃ ipso C₆H₅), 128.2e126.3

(30ꢃC₆H₅), 118.3 (CeH thiazol), 103.5 (C-5), 100.2 (C-2), 80.9

(PhCHCH₂OBn), 76.9 (C-3⁰), 76.5 (C-2⁰), 74.7, 73.4 (C-4⁰, C-5⁰), 74.7

(PhCHCH₂OBn), 73.4, 73.1, 73.1, 71.9, 71.4 (5ꢃ PhCH₂, PhCHCH₂OBn),

70.8 (C-1⁰), 69.7 (C-1⁰), 69.0 (C-6⁰), 35.5 (C-1⁰⁰), 33.4 (C-3), 27.3 (C-4).

ESIMS: MH^þ, found, 931.2. C₅₈H₆₀NO₈S requires 931.2.

4.1.7. Methyl (R)-2-phenyl-2-{[(2S,4S)-4-(2,3,4,6-tetra-O-benzyl-

D-mannopyranosyl)methyl-6-(thiazol-2-yl)-3,4-dihydro-2H-pyran-2-

yl]oxy}acetate (16). According to the same procedure described for

the preparation of compound 15, compound 11 (9.0 g, 13.3 mmol)

and chiral vinyl ether (R)-12 (3.9 g, 20.3 mmol) afforded 9.3 g (80%)

of compound 16 as a colorless foam; [Found: C, 71.70; H, 5.95.

C₅₂H₅₃NO₉S requires C, 71.95; H, 6.15%]; R_f¼0.30 (light petroleum/

4.1.9. (2S,4S)-2-[(R)-2-(Benzyloxy)-1-phenylethoxy]-4-[(2,3,4,6-

tetra-O-benzyl-a-D-mannopyranosyl)methyl]-6-(thiazol-2-yl)-3,4-di-

hydro-2H-pyran (18). Using the same procedure as described for

the preparation of compound 17, compound 14 (6.1 g, 7.03 mmol)

was converted to compound 18 (pale yellow viscous oil, 4.6 g, 70%);

[Found: C, 74.98; H, 6.25. C₅₈H₅₉NO₈S requires C, 74.89; H, 6.39%];

ethyl acetate, 2:1); [

²⁰ꢂ27.5 (c 1.48, CHCl₃); n_max3020,1748,1497,

1454, 1268, 1096, 1028 cm^ꢂ1; ¹H NMR (500 MHz, CDCl₃) 7.72 (d, 1H,

H-thiazol, J 3.1 Hz), 7.48e7.10 (m, 26H, 5ꢃ C₆H₅, H-thiazol), 6.00

(d,1H, J_5,43.5 Hz, H-5), 5.48 (s, 1H, PhCHCOOCH₃), 5.42 (dd, 1H, J_2,3ax

€

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Z. Lovyova et al. / Tetrahedron 67 (2011) 4967e4979

R_f¼0.35 (light petroleum/ethyl acetate, 3:1); [

]

ꢂ0.7 (c 1.57,

J_3eq,21.9 Hz, H-3_eq), 2.11 (m, 1H, H-1⁰⁰a), 1.75 (ddd, 1H, J_3eq,3ax

13.3 Hz, J_3ax,48.5 Hz, J_3ax,26.7 Hz, H-3_ax), 1.42 (m, 1H, H-1⁰⁰b); ¹³C

NMR (125 MHz, CDCl₃) 164.5 (thiazol C-2), 143.7 (C-6), 142.9 (CeH

thiazol), 139.7, 138.6, 138.5, 138.5, 138.4, 138.2 (6ꢃ ipso C₆H₅),

128.4e126.6 (30ꢃ C₆H₅), 118.7 (CeH thiazol), 103.3 (C-5), 100.9 (C-

2), 85.3 (C-3⁰), 81.1 (PhCHCH₂OBn), 79.8 (C-5⁰), 76.2, 75.6 (C-2⁰,

C-4⁰), 75.2 (C-1⁰), 75.1, 74.9, 74.4, 73.4, 73.3, 72.6 (5ꢃ PhCH₂,

PhCHCH₂OBn), 69.7 (C-6⁰), 37.7 (C-1⁰⁰), 34.5 (C-3), 27.2 (C-4). ESIMS:

MH^þ, found, 931.2. C₅₈H₆₀NO₈S requires 931.2.

CHCl₃); n_max3011, 1723,1699, 1496, 1454, 1363, 1266, 1099,

1028 cm^ꢂ^{1 1}H NMR (500 MHz, CDCl₃) 7.63 (d, 1H, H-thiazol, J

;

3.2 Hz), 7.36e7.14 (m, 30H, 6ꢃ C₆H₅), 7.07 (d, 1H, H-thiazol, J

3.2 Hz), 5.88 (d,1H, J_5,43.5 Hz, H-5), 5.47 (dd, 1H, J_2,3ax6.5 Hz, J_2,3eq

1.9 Hz, H-2), 4.95 (dd, 1H, J 8.0 Hz, J 3.5 Hz, PhCHCH₂OBn),

4.70e4.47 (m, 10H, 5ꢃ OeCH₂ePh), 4.17 (m, 1H, H-1⁰), 3.90e3.83

(m, 2H, H-4⁰, H-5⁰), 3.83e3.76 (m, 2H, H-6⁰a, H-3⁰), 3.73 (dd, 1H,

J_{6 a,6 b}10.2 Hz, J_{6 b,5}3.6 Hz, H-6⁰b), 3.68 (dd, 1H, J 10.7 Hz, J 8.0 Hz,

PhCHCH_2aOBn), 3.60 (dd, 1H, J 10.7 Hz, J 3.5 Hz, PhCHCH_2bOBn),

3.55 (dd, 1H, J_{2 ,3}4.9 Hz, J_{2 ,1}3.0 Hz, H-2 ), 2.72 (m, 1H, H-4), 2.23

(ddd, 1H, J_3eq,3ax13.3 Hz, J_3eq,46.7 Hz, J_2,3eq1.9 Hz, H-3_eq), 1.93 (m,

1H, H-1⁰⁰a), 1.83 (ddd, 1H, J_3eq,3ax13.3 Hz, J_3ax,47.5 Hz, J_2,3ax6.5 Hz,

H-3_ax), 1.69 (m, 1H, H-1⁰⁰b); ¹³C NMR (125 MHz, CDCl₃) 164.2

(thiazol C-2), 143.6 (C-6), 142.8 (CeH thiazol), 139.6, 138.3, 138.2,

138.1, 138.1, 138.1 (6ꢃ ipso C₆H₅), 128.3e126.5 (30ꢃ C₆H₅), 118.4

(CeH thiazol), 105.0 (C-5), 100.7 (C-2), 81.0 (PhCHCH₂OBn), 77.0,

74.7, 73.5 (C-3⁰, C-4⁰, C-5⁰), 76.6 (C-2⁰), 74.8, 73.4, 73.3, 73.1, 72.1, 71.5

(5ꢃ PhCH₂, PhCHCH₂OBn), 69.7 (C-1⁰), 68.8 (C-6⁰), 35.4 (C-1⁰⁰), 32.1

(C-3), 27.1 (C-4). ESIMS: MH^þ, found, 931.2. C₅₈H₆₀NO₈S requires

931.2.

4.1.12. (2R,4R)-2-[(S)-2-(Benzyloxy)-1-phenylethoxy]-4-[(2,3,4,6-

tetra-O-benzyl-a-D-mannopyranosyl)methyl]-6-formyl-3,4-dihydro-

ꢂ

2H-pyran (21). Molecular sieves (4 A; 7.2 g) were added to a solu-

tion of compound 17 (5.3 g, 5.68 mmol) in acetonitrile (160 mL),

and methyl triﬂate (0.96 mL, 8.45 mmol) was added dropwise. After

stirring at room temperature for 15 min, MeOH (5 mL) was added,

and the solvent was evaporated in vacuo. The residue was treated

with MeOH (80 mL), and then, NaBH₄(0.7 g, 18.6 mmol) was added

in portions. After stirring at room temperature for 15 min, acetone

(15 mL) was added, the reaction mixture was ﬁltered through Super

Cel and the ﬁltrate was evaporated in vacuo. The residue was dis-

solved in acetonitrile (60 mL), and a solution of AgNO₃(2.1 g,

12.36 mmol) in water (6 mL) was added under vigorous stirring.

After stirring for 10 min, phosphate buffer (20 mL; pH 7) was added,

and after 10 min, the acetonitrile was evaporated in vacuo, and the

residue was partitioned between dichloromethane and phosphate

buffer (pH 7). The organic phase was dried, the solvent was evap-

orated, and the residue was ﬂash-chromatographed through

4.1.10. (2R,4R)-2-[(S)-2-(Benzyloxy)-1-phenylethoxy]-4-[(2,3,4,6-

tetra-O-benzyl-b-D-mannopyranosyl)methyl]-6-(thiazol-2-yl)-3,4-di-

hydro-2H-pyran (19). Using the same procedure as described for

the preparation of compound 17, compound 15 (7.1 g, 8.2 mmol)

was converted to compound 19 (pale yellow viscous oil, 5.3 g, 70%);

[Found: C, 75.05; H, 6.55. C₅₈H₅₉NO₈S requires C, 74.89; H, 6.39%];

R_f¼0.35 (light petroleum/ethyl acetate, 3:1); [

]

þ6.3 (c 1.81,

a short silica gel column in light petroleum/ethyl acetate

(7:1/5:1). This procedure resulted in a yield of 3.7 g (73%) of al-

dehyde 21 as a viscous oil; [Found: C, 76.74; H, 6.52. C₅₆H₅₈O₉re-

CHCl₃); n_max3011, 1722, 1700, 1496, 1454, 1363, 1257, 1116,

1028 cm^ꢂ^{1 1}H NMR (500 MHz, CDCl₃) 7.63 (d, 1H, J 3.2 Hz, H-

;

thiazol,), 7.42e7.14 (m, 30H, 6ꢃ C₆H₅), 7.03 (d, 1H, J 3.2 Hz, H-

thiazol,), 5.89 (d,1H, J_5,43.2 Hz, H-5), 5.39 (dd, 1H, J_2,3ax7.1 Hz, J_2,3eq

2.3 Hz, H-2), 4.98 (d, 1H, J 10.8 Hz, OeCH₂ePh), 4.94 (dd, 1H, J

8.3 Hz, J 3.4 Hz, PhCHCH₂OBn), 4.89 (d, 1H, J 10.8 Hz, OeCH₂ePh),

quires C, 76.86; H, 6.68%]; R_f¼0.3 (light petroleum/ethyl acetate,

3:1); [

]

þ5.7 (c 1.2, CHCl₃); n_max3011, 2926, 2865, 1697, 1496,

1454, 1364, 1093, 1028, 986 cm^ꢂ^{1 1}H NMR (500 MHz, CDCl₃) 8.75

;

(s, 1H, HCO), 7.40e7.10 (m, 30H, 6ꢃ C₆H₅), 5.81 (d, 1H, J_5,44.3 Hz, H-

4.78e4.43 (m, 8H, 4ꢃ OeCH₂ePh), 3.97 (dd, 1H, J_{4 ,5}¼J_{4 ,3}9.5 Hz,

H-4⁰), 3.80e3.55 (m, 6H, PhCHCH_2aOBn, PhCHCH_2bOBn, H-6⁰a, H-

6⁰b, H-2⁰, H-3⁰), 3.52e3.42 (m, 2H, H-1⁰, H-5⁰), 2.49 (m,1H, H-4), 2.16

(m, 1H, H-1⁰⁰a), 2.07 (ddd, 1H, J_3eq,3ax13.1 Hz, J_3eq,46.9 Hz, J_2,3eq

2.3 Hz, H-3_eq), 1.75 (ddd, 1H, J_3eq,3ax13.1 Hz, J_3ax,27.1 Hz, J_3ax,4

6.7 Hz, H-3_ax), 1.58 (m, 1H, H-1⁰⁰b); ¹³C NMR (125 MHz, CDCl₃) 164.1

(thiazol C-2); 143.5 (C-6), 142.6 (CeH thiazol), 139.4, 138.3, 138.2,

138.1, 138.1, 137.9 (6ꢃ ipso C₆H₅), 128.2e126.3 (30ꢃC₆H₅), 118.5

(CeH thiazol), 104.2 (C-5), 100.7 (C-2), 85.2 (C-3⁰), 81.2

(PhCHCH₂OBn), 79.7 (C-5⁰), 75.3, 75.1, 74.9 (C-1⁰, C-2⁰, C-4⁰), 74.9,

74.6, 74.0, 73.2, 73.1, 72.3 (5ꢃ PhCH₂, PhCHCH₂OBn), 69.4 (C-6⁰),

36.5 (C-1⁰⁰), 32.7 (C-3), 27.0 (C-4). ESIMS: MH^þ, found, 931.2.

C₅₈H₆₀NO₈S requires 931.2.

5), 5.55 (m, 1H, H-2), 4.93 (dd, 1H, J 8.1, 3.5 Hz, PhCHCH₂OBn),

4.71e4.45 (m, 10H, 5ꢃ OeCH₂ePh), 4.06 (ddd, 1H, J_{1 ,1 a}10.1₀Hz,

J_{1 ,1 b}5.2 Hz, J_{1 ,2}2.8 Hz, H-1 ), 3.98e3.73 (m, 4H, H-3 , H-4 , H-5 , H-

6⁰a), 3.68 (dd, 1H, J_{6 a,6 b}10.2 Hz, J_{6 b,5}3.7 Hz, H-6⁰b), 3.62 (m, 1H,

PhCHCH_2aOBn), 3.57e3.48 (m, 2H, H-2⁰, PhCHCH_2bOBn), 2.64 (m,

1H, H-4), 2.10e1.91 (m, 3H, H-1⁰⁰a, H-3_eq, H-3_ax), 1.85 (m, 1H, H-

1⁰⁰b); ¹³C NMR (125 MHz, CDCl₃) 186.3 (HCO); 148.7 (C-6), 139.3,

138.2, 138.1, 138.1 (6ꢃ ipso C₆H₅), 128.4e126.5 (30ꢃ C₆H₅), 125.2 (C-

5), 98.3 (C-2), 79.8 (PhCHCH₂OBn), 76.8, 74.8, 73.7 (C-3⁰, C-4⁰, C-5⁰),

76.4 (C-2⁰), 74.6 (PhCHCH₂OBn), 73.3, 73.2, 73.1, 72.4, 71.8 (5ꢃ

PhCH₂), 69.1 (C-1⁰), 68.8 (C-6⁰), 35.7 (C-1⁰⁰), 32.1 (C-3), 26.5 (C-4).

ESIMS: MNH^þ₄, found 892.6. C₅₆H₆₂NO₉requires 892.4.

4.1.13. (2S,4S)-2-[(R)-2-(Benzyloxy)-1-phenylethoxy]-4-[(2,3,4,6-

4.1.11. (2S,4S)-2-[(R)-2-(Benzyloxy)-1-phenylethoxy]-4-[(2,3,4,6-

tetra-O-benzyl-a-D-mannopyranosyl)methyl]-6-formyl-3,4-dihydro-

tetra-O-benzyl-

-mannopyranosyl)methyl]-6-(thiazol-2-yl)-3,4-di-

2H-pyran (22). Using the same procedure as described for the

preparation of compound 21, compound 18 (5.3 g, 5.68 mmol) was

converted to aldehyde 22 (viscous oil, 3.8 g, 75%); [Found: C, 76.65;

hydro-2H-pyran (20). Using the same procedure as described for

the preparation of compound 17, compound 16 (6.1 g, 7.03 mmol)

was converted to compound 20 (pale yellow viscous oil, 4.6 g, 70%);

H, 6.56. C₅₆H₅₈O₉requires C, 76.86; H, 6.68%]; R_f¼0.3 (light petro-

[Found: C, 74.78; H, 6.25. C₅₈H₅₉NO₈S requires C, 74.89; H, 6.39%];

leum/ethyl acetate, 3:1); [

]

þ10.0 (c 1.05, CHCl₃); n_max3019,

R_f¼0.35 (light petroleum/ethyl acetate, 3:1); [

]

ꢂ13.8 (c 1.26,

2925, 2865, 1696, 1496, 1454, 1364, 1096, 1028, 986 cm^ꢂ1; ¹H NMR

(500 MHz, CDCl₃) 8.75 (s, 1H, HCO), 7.39e7.08 (m, 30H, 6ꢃ C₆H₅);

5.94 (d, 1H, J_5,44.3 Hz, H-5); 5.56 (m,1H, H-2); 4.95 (dd, 1H, J 8.1,

3.6 Hz, PhCHCH₂OBn), 4.71e4.45 (m, 10H, 5ꢃ OeCH₂ePh), 4.15

CHCl₃); n_max3011, 1722, 1699, 1497, 1454, 1363, 1266, 1098,

1028 cm^ꢂ^{1 1}H NMR (500 MHz, CDCl₃) 7.66 (d, 1H, H-thiazol,

;

J 3.2 Hz), 7.42e7.16 (m, 30H, 8ꢃ C₆H₅), 7.13 (d, 1H, H-thiazol, J

3.2 Hz), 5.87 (d,1H, J_5,43.2 Hz, H-5), 5.47 (dd, 1H, J_2,3ax6.7 Hz, J_2,3eq

1.9 Hz, H-2), 5.10e4.95 (m, 2H, PhCHCH₂OBn, OeCH₂ePh), 4.88 (d,

1H, J 10.8 Hz, OeCH₂ePh), 4.90e4.48 (m, 8H, 4ꢃ OeCH₂ePh), 3.94

(ddd,1H, J_{1 ,1 a}11.0 Hz, J_{1 ,1 b}4.8 Hz, J_{1 ,2}2.7 Hz, H-1 ), 3.86e3.71 (m,

4H, H-3⁰, H-4⁰, H-5⁰, H-6⁰a), 3.69e3.60 (m, 2H, H-6⁰b,

PhCHCH_2aOBn), 3.60e3.53 (m, 2H, H-2⁰, PhCHCH_2bOBn), 2.59 (m,

1H, H-4), 2.03e1.87 (m, 3H, H-1⁰⁰a, H-3_eq, H-3_ax), 1.78 (m, 1H, H-

1⁰⁰b); ¹³C NMR (125 MHz, CDCl₃) 186.3 (HCO), 148.4 (C-6), 139.0,

138.0, 138.0, 137.9, 137.8 (6ꢃ ipso C₆H₅), 128.2e127.2 (30ꢃ C₆H₅),

126.4 (C-5), 98.1 (C-2) 79.3 (PhCHCH₂OBn), 76.4, 76.3 (C-2⁰, C-3⁰),

(dd, 1H, J_{4 ,5}¼J_{4 ,3}9.4 Hz, H-4⁰), 3.80e3.68 (m, 4H, PhCHCH_2aOBn,

PhCHCH_2bOBn, H-6⁰a, H-6⁰b), 3.67e3.57 (m, 2H, H-2⁰, H-3⁰), 3.53

(m, 1H, H-1⁰), 3.44 (ddd, 1H, J_{4 ,5}9.4 Hz, J_{5 ,6 b}5.0 Hz, J_{5 ,6 a}1.7 Hz, H-

5⁰), 2.68 (m, 1H, H-4), 2.21 (ddd, 1H, J_3eq,3ax13.3 Hz, J_3eq,46.6 Hz,

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Z. Lovyova et al. / Tetrahedron 67 (2011) 4967e4979

4975

74.8, 73.3 (C-4⁰, C-5⁰), 74.5 (PhCHCH₂OBn), 73.4, 73.1, 72.0, 71.4 (5ꢃ

PhCH₂), 71.0 (C-1⁰), 68.9 (C-6⁰), 34.8 (C-1⁰⁰), 30.9 (C-3), 27.7 (C-4).

ESIMS: MNH^þ₄, found 892.6. C₅₆H₆₂NO₉requires 892.4.

mineral oil (1 g, 25 mmol), the mixture was stirred at room tem-

perature for 1 h. Benzyl bromide (3.1 mL, 25.8 mmol) and tetrabu-

tylammonium iodide (0.49 g, 1.3 mmol) were added, and the

reaction mixture was heated at 40 ^ꢀC for 4 h. After stirring at room

temperature for 14 h, MeOH (5 mL) was added, the solvent was

evaporated in vacuo, and the residue was partitioned between

dichloromethane and a saturated solution of NaHCO₃. The organic

layer was dried, the solvent was removed in vacuo, and the residue

was chromatographed on silica gel in light petroleum/ethyl acetate

(12:1/8:1) to give 2.7 g (60%) of compound 25 as a viscous oil;

4.1.14. (2R,4R)-2-[(S)-2-(Benzyloxy)-1-phenylethoxy]-4-[(2,3,4,6-

tetra-O-benzyl-b-D-mannopyranosyl)methyl]-6-formyl-3,4-dihydro-

2H-pyran (23). Using the same procedure as described for the

preparation of compound 21, compound 19 (5.1 g, 5.45 mmol) was

converted to aldehyde 23 (viscous oil, 3.5 g, 73%); [Found: C, 76.74;

H, 6.88. C₅₆H₅₈O₉requires C, 76.86; H, 6.68%]; R_f¼0.3 (light petro-

leum/ethyl acetate, 3:1); [

]

²⁰þ5.2 (c 1.24, CHCl₃); n_max3020, 2928,

[Found: C, 78.26; H, 6.75. C₇₀H₇₄O₁₀requires C, 78.19; H, 6.94%];

2863, 1697, 1497, 1454, 1364, 1088, 1028, 986 cm^ꢂ1

;

¹H NMR

R_f¼0.56 (light petroleum/ethyl acetate, 3:1); [

]

þ2.5 (c 0.73,

(500 MHz, CDCl₃) 8.78 (s, 1H, HCO), 7.43e7.15 (m, 30H, 6ꢃ C₆H₅),

5.84 (d, 1H, J_H-5,Hꢂ44.10 Hz, H-5), 5.5 (m, 1H, H-2), 4.98 (d, 1H, J

11.7 Hz, OeCH₂ePh), 4.95 (dd, 1H, J 7.7, 3.8 Hz, PhCHCH₂OBn), 4.89

(d, 1H, J 10.8 Hz, OeCH₂ePh), 4.78e4.47 (m, 8H, 4ꢃ OeCH₂ePh),

CHCl₃); n_max3011, 2922, 2867, 1496, 1454, 1364, 1087, 1028 cm^ꢂ1; ¹H

NMR (500 MHz, CDCl₃) 7.42e7.13 (m, 40H, 8ꢃ C₆H₅); 4.91 (dd, 1H, J

7.8, 4.1 Hz, PhCHCH₂OBn), 4.73 (dd,1H, J_1,2ax9.4 Hz, J_1,2eq1.6 Hz, H-1),

4.69 (d, 1H, H-1, J 11.2 Hz, OeCH₂ePh), 4.60e4.30 (m, 13H,

3.92 (dd, 1H, J_{4 ,5}¼J_{4 ,3}9.5 Hz, H-4⁰), 3.79e3.55 (m, 6H, H-2⁰, H-3⁰,

OeCH₂ePh), 4.08 (ddd, 1H, J_{1 ,1 b}7.8 Hz, J_{1 ,1 a}4.4 Hz, J_{1 ,2}3.1 Hz,

H-6⁰a, H-6⁰b, PhCHCH_2aOBn, PhCHCH_2bOBn), 3.48e3.41 (m, 2H, H-

H-1⁰), 3.85 (dd, 1H, J_{4 ,5}¼J_{3 ,4}6.7 Hz, H-4⁰), 3.76e3.58 (m, 7H, H-3⁰,

1⁰, H-5⁰), 2.56 (m, 1H, H-4), 2.15 (ddd, 1H, J_{1 a,1 b}13.4, J 9.9, J 6.0 Hz,

H-1⁰⁰a), 1.95 (ddd, 1H, J_3eq,3ax13.9 Hz, J_4,3eq7.1 Hz, J_2,3eq2.2 Hz, H-

3_eq), 1.84 (ddd, 1H, J_3eq,3ax13.9 Hz, J_2,3ax¼J_4,3ax4.1 Hz, H-3_ax), 1.57

H-5⁰, H-6a, H-6b, H-6⁰a, PhCHCH_2aOBn, PhCHCH_2bOBn), 3.53 (dd,1H,

J_{6 b,6 a}11.2 Hz, J_{6 b,5}1.6 Hz, H-6⁰b), 3.46 (dd, 1H, J_{2 ,3}4.2 Hz, J_{2 ,1}

3.1 Hz, H-2⁰), 3.30 (ddd, 1H, J_4,59.4 Hz, J_5,6a3.9 Hz, J_5,6b1.8 Hz, H-5),

3.16 (dd, 1H, J_4,5¼J_3,49.4 Hz, H-4), 2 0.18 (ddd, 1H, J_2eq,2ax12.6 Hz,

(ddd, 1H, J_{1 a,1 b}13.4 Hz, J 8.6, 2.3 Hz, H-1⁰⁰b); ¹³C NMR (125 MHz,

CDCl₃) 186.3 (HCO), 148.6 (C-6), 139.2, 138.5, 138.4, 138.3, 138.1 (6ꢃ

ipso C₆H₅), 128.4e127.2 (30ꢃ C₆H₅), 126.6 (C-5), 98.5 (C-2), 85.3 (C-

3⁰), 79.8 (PhCHCH₂OBn), 79.8 (C-5⁰), 76.2, 76.1, 75.4 (C-1⁰, C-2⁰, C-4⁰),

75.1, 74.7, 74.4, 73.4, 73.2 (5ꢃ PhCH₂), 72.6 (PhCHCH₂OBn), 69.8 (C-

6⁰), 36.3 (C-1⁰⁰), 31.1 (C-3), 27.5 (C-4). ESIMS: MNH^þ₄, found 892.6.

C₅₆H₆₂NO₉requires 892.4.

J_2eq,33.7 Hz, J_2eq,11.6 Hz, H-2_eq), 1.86 (ddd, 1H, J_{1 a,1 b}13.8 Hz, J_{1 a,1}

4.4 Hz, J_{1 a,3}3.9 Hz, 1⁰⁰a), 1.62 (m, 1H, H-3), 1.42 (ddd, 1H, J_2eq,2ax

12.8 Hz, J_2ax,3¼J_2ax,19.4 Hz, H-2_ax), 1.33 (ddd, 1H, J_{1 a,1 b}13.8 Hz, J_{1 b,3}

8.3 Hz, J_{1 b,1}7.8 Hz, H-1 b); ¹³C NMR (125 MHz, CDCl₃) 140.3, 138.6,

138.5, 138.4, 138.3, 138.2, 138.1, 138.0 (8ꢃ ipso C₆H₅), 128.3e126.7

(40ꢃ C₆H₅), 101.5 (C-1), 79.3 (PhCHCH₂OBn), 78.3, 78.2 (C-5, C-4),

77.3 (C-3⁰), 75.9 (C-2⁰), 74.9 (C-4⁰), 74.7, 74.1, 73.7, 73.4, 73.3, 73.2,

72.2, 71.4 (7ꢃ PhCH₂, PhCHCH₂OBn), 73.4 (C-5⁰), 72.5 (C-1⁰), 69.2

(C-6⁰, C-6), 38.7 (C-3), 36.9 (C-2), 32.3 (C-1⁰⁰). ESIMS: MNH^þ₄, found

1092.7. C₇₀H₇₈NO₁₀requires 1092.6.

4.1.15. (2S,4S)-2-[(R)-2-(Benzyloxy)-1-phenylethoxy]-4-[(2,3,4,6-

tetra-O-benzyl-b-D-mannopyranosyl)methyl]-6-formyl-3,4-dihydro-

2H-pyran (24). Using the same procedure as described for the

preparation of compound 21, compound 20 (4.8 g, 5.16 mmol) was

converted to aldehyde 24 (viscous oil, 3.4 g, 75%); [Found: C, 76.59;

H, 6.75. C₅₆H₅₈O₉requires C, 76.86; H, 6.68%]; R_f¼0.3 (light petro-

4.1.17. (R)-2-(Benzyloxy)-1-fenylethyl 2,3-dideoxy-3-C-[(2,3,4,6-tetra-

O-benzyl-a-D-mannopyranosyl)methyl]-4,6-di-O-benzyl-b-L-ara-

bino-hexopyranoside (26). Using the same procedure as described

for the preparation of compound 25, aldehyde 22 (1.9 g, 2.17 mmol)

was converted to compound 26 (viscous oil, 1.4 g, 60%); [Found: C,

78.05; H, 7.05. C₇₀H₇₄O₁₀requires C, 78.19; H, 6.94%]; R_f¼0.58 (light

leum/ethyl acetate, 3:1); [

]

²⁰ꢂ1.9 (c 1.13, CHCl₃); n_max3020, 2928,

2861, 1697, 1497, 1454, 1363, 1097, 1028, 987 cm^ꢂ1

;

¹H NMR

(500 MHz, CDCl₃) 8.82 (s, 1H, HCO); 7.43e7.15 (m, 30H, 6ꢃ C₆H₅),

5.71 (d, 1H, J_5,44.1 Hz, H-5); 5.57 (m, 1H, H-2), 5.10 (d, 1H, J 11.7 Hz,

OeCH₂ePh), 4.95 (dd, 1H, J 8.1, 3.5 Hz, PhCHCH₂OBn), 4.89 (d, 1H, J

10.8 Hz, OeCH₂ePh), 4.8₀2e4.46 (m, 8H, 4ꢃ OeCH₂ePh), 3.92 (dd,

petroleum/ethyl acetate, 3:1); [

]

²⁰þ8.6 (c 1.03, CHCl₃); n_max3010,

2918, 2866, 1496, 1454, 1363, 1089, 1028 cm^ꢂ1; ¹H NMR (500 MHz,

CDCl₃) 7.40e7.12 (m, 40H, 8ꢃ C₆H₅), 4.88 (dd, 1H, J 7.5, 4.0 Hz,

PhCHCH₂OBn), 4.78 (dd, 1H, J_1,2ax9.4 Hz, J_1,2eq1.8 Hz, H-1), 4.77 (d,

1H, J 11.5 Hz, OeCH₂ePh), 4.63e4.32 (m, 13H, OeCH₂ePh), 4.08

1H, J_{4 ,5}¼J_{4 ,3}9.2 Hz, H-4 ), 3.75 (dd, 1H, J_{6 a,6 b}10.7 Hz, J_{6 a,5}1.4 Hz,

H-6⁰a), 3.71e3.64 (m, 2H, H-6⁰b, PhCHCH_2aOBn), 3.64e3.56 (m, 3H,

H-2⁰, H-3⁰, PhCHCH_2bOBn), 3.42e3.34 (m, 2H, H-1⁰, H-5⁰), 2.59 (m,

1H, H-4), 2.15 (m, 1H, H-1⁰⁰a), 2.03 (ddd, 1H, J_3eq,3ax13.8 Hz, J_3eq,4

7.4 Hz, J_3eq,22.4 Hz, H-3_eq),1.88 (ddd,1H, J_3eq,3ax13.8 Hz, J_3eq,4¼J_3eq,2

4.0 Hz, H-3_ax), 1.78 (m, 1H, H-1⁰⁰b); ¹³C NMR (125 MHz, CDCl₃) 186.5

(HCO), 148.9 (C-6), 139.1, 138.5, 138.4, 138.3, 138.2 (6ꢃ ipso C₆H₅);

128.4e126.6 (30ꢃ C₆H₅), 125.2 (C-5), 98.5 (C-2), 85.2 (C-3⁰), 79.9 (C-

5⁰), 79.2 (PhCHCH₂OBn), 76.1 (C-2⁰), 75.7 (C-1⁰), 75.4 (C-4⁰), 75.1,

74.7, 74.4, 73.4, 73.3, 72.6 (5ꢃ PhCH₂, PhCHCH₂OBn), 69.8 (C-6⁰),

36.8 (C-1⁰⁰), 32.4 (C-3), 26.6 (C-4). ESIMS: MNH^þ₄, found 892.6.

C₅₆H₆₂NO₉requires 892.4.

(ddd, 1H, J_{1 ,1 b}11.9 Hz, J_{1 ,2}¼J_{1 ,1 a}3.2 Hz, H-1⁰), 3.88 (dd, 1H,

0 00

J_{4 ,5}¼J_{3 ,4}7.3 Hz, H-4⁰), 3.77e3.57 (m, 7H, H-3⁰, H-5⁰, H-6a, H-6b,

H-6⁰a, PhCHCH_2aOBn, PhCHCH_2bOBn), 3.52 (dd, 1H, J_{6 a,6 b}11.1 Hz,

J_{6 ,5}1.5 Hz, H-6 b), 3.43 (dd, 1H, J_{2 ,3}3.4 Hz, J_{2 ,1}3.2 Hz, H-2 ), 3.30

(ddd, 1H, J_5,49.6 Hz, J_5,6a3.9 Hz, J_5,6b2.1 Hz, H-5), 3.14 (dd, 1H,

J_4,5¼J_3,49.6 Hz, H-4), 2.21 (ddd,1H, J_2eq,2ax12.8 Hz, J_2eq,33.9 Hz, J_2eq,1

1.8 Hz, H-2_eq), 2.06 (m, 1H, H-1⁰⁰a), 1.90 (m, 1H, H-3), 1.30 (ddd, 1H,

J_2eq,2ax¼J_2ax,312.8 Hz J_2ax,19.4 Hz, H-2_ax), 0.85 (m, 1H, H-1⁰⁰b); ¹³C

NMR (125 MHz, CDCl₃) 140.3, 138.6, 138.5, 138.5, 138.3, 138.3, 138.1,

138.1 (8ꢃ ipso C₆H₅), 128.4e126.7 (40ꢃ C₆H₅), 101.6 (C-1), 79.3

(PhCHCH₂OBn), 78.1 (C-5, C-3⁰), 77.7 (C-4), 76.5 (C-2⁰), 75.0 (C-4⁰),

74.4, 73.9, 73.8, 73.4, 73.2, 72.9, 71.9, 71.4 (7ꢃ PhCH₂,

PhCHCH₂OBn), 72.5 (C-5⁰), 69.4 (C-1⁰), 69.2 (C-6⁰, C-6), 35.7 (C-3),

35.6 (C-2), 31.2 (C-1⁰⁰). ESIMS: MNH^þ₄, found 1092.7. C₇₀H₇₈NO₁₀

requires 1092.6.

4.1.16. (S)-2-Benzyloxy-1-phenylethyl 2,3-dideoxy-3-C-[(2,3,4,6-tetra-

O-benzyl-a-D-mannopyranosyl)methyl]-4,6-di-O-benzyl-b-D-arabino-

hexopyranoside (25). A 2 M solution of BH₃$Me₂S in tetrahydrofuran

(7.4 mL,14.7 mmol) was added dropwise to a solution of aldehyde 21

(3.7 g, 4.2 mmol) in tetrahydrofuran (80 mL) that was pre-cooled to

^ꢀC, and the reaction mixture was stirred at room temperature for

16 h. Then, a 30% NaOH solution (4.6 mL) and a 30% H₂O₂(4.6 mL)

were added in succession. The mixture was stirred at room tem-

perature for 30 min and partitioned between ethyl acetate and

a saturated NaCl solution. The organic phase was dried, the ethyl

acetate evaporated in vacuo, and the residue was dissolved in tet-

rahydrofuran (150 mL). After addition of a 60% suspension of NaH in

4.1.18. (S)-2-(Benzyloxy)-1-fenylethyl 2,3-dideoxy-3-C-[(2,3,4,6-tetra-

O-benzyl-b-D-mannopyranosyl)methyl]-4,6-di-O-benzyl-b-D-ara-

bino-hexopyranoside (27). Using the same procedure as described

for the preparation of compound 25, aldehyde 23 (3.4 g, 3.9 mmol)

was converted to compound 27 (viscous oil, 2.9 g, 70%); [Found: C,

78.35; H, 6.74. C₇₀H₇₄O₁₀requires C, 78.19; H, 6.94%]; R_f¼0.6 (light

€

Z. Lovyova et al. / Tetrahedron 67 (2011) 4967e4979

4976

petroleum/ethyl acetate, 3:1); [

]

²⁰ꢂ4.9 (c 0.78, CHCl₃); n_max3011,

1497, 1454, 1364, 1088, 1028 cm^ꢂ^{1 1}H NMR (500 MHz, CDCl₃)

;

2921, 2864, 1497, 1454, 1364, 1086, 1028 cm^ꢂ1; ¹H NMR (500 MHz,

CDCl₃) 7.40e7.10 (m, 40H, 8ꢃ C₆H₅), 4.80 (d, 1H, J 11.8 Hz,

OeCH₂ePh), 4.90 (dd, 1H, J 7.6, 3.9 Hz, PhCHCH₂OBn), 4.86 (d, 1H, J

11.8 Hz, OeCH₂ePh), 4.75 (dd, 1H, J_1,2ax9.5 Hz, J_1,2eq1.9 Hz, H-1),

7.47e7.13 (m, 35H, 7ꢃ C₆H₅), 5.53 (d, 1H, J_1,2ax5.4 Hz, H-1), 4.73e4.40

(m, 12H, 6ꢃ OeCH₂ePh), 4.26 (m, 1H, H-5), 4.10 (m, 1H, H-1⁰),

3.85e3.73 (m, 3H, H-4⁰, H-5⁰, H-6a), 3.72e3.64 (m, 2H, H-3⁰, H-6⁰a),

3.61 (dd, 1H, J 1.4, 10.7 Hz, H-6⁰b), 3.50 (dd, 1H, J 3.3, 4.1 Hz, H-2⁰), 3.31

(dd, 1H, J_4,59.7 Hz, J_3,49.5 Hz, H-4), 2.41 (ddd, 1H, J_2eq,2ax13.9 Hz, J_2eq,3

3.9 Hz, J_2eq,1w0 Hz, H-2_eq), 2.04 (m, 1H, H-3), 1.94 (m, 1H, H-1⁰⁰a), 1.86

(ddd, 1H, J_2eq,2ax13.9 Hz, J_2ax,312.6 Hz, J_2ax,15.4 Hz, H-2_ax); 1.27 (m, 1H,

H-1⁰⁰b); ¹³C NMR (125 MHz, CDCl₃) 138.4, 138.3, 138.3, 138.2, 138.1,

137.9, 135.7 (7ꢃ ipso C₆H₅), 130.8e126.5 (35ꢃ C₆H₅), 84.7 (C-1), 78.4

(C-4), 77.2 (C-3⁰), 77.3 (C-3⁰), 76.1 (C-2⁰), 74.9 (C-4⁰), 73.9, 73.8, 73.4,

73.3, 72.0, 71.4 (6ꢃ PhCH₂), 73.5 (C-5⁰), 72.6 (C-5), 72.2 (C-1⁰), 69.4 (C-

6), 69.3 (C-6⁰), 37.1 (C-3), 36.4 (C-2), 31.6 (C-1⁰⁰). ESIMS: MNH^þ₄, found

974.8. C₆₁H₆₈NO₈S requires 974.5.

4.72e4.29 (m, 12H, 6ꢃ OeCH₂ePh), 3.95 (dd, 1H, J_{4 ,5}¼J_{3 ,4}9.5 Hz,

H-4⁰), 3.78e3.66 (m, 4H, H-2⁰, H-6a, H-6b, PhCHCH_2aOBn),

3.66e3.57 (m, 2H, H-6⁰a, PhCHCH_2bOBn), 3.56e3.48 (m, 2H, H-3⁰,

H-6⁰b), 3.42e3.36 (m, 2H, H-1⁰, H-5⁰), 3.34 (ddd, 1H, J_5,49.7 Hz, J_5,6b

4.0 Hz, J_5,6a2.1 Hz, H-5), 3.14 (dd, 1H, J_4,5¼J_3,4¼9.7 Hz, H-4), 2.37 (m,

1H, H-1⁰⁰a), 2.0 (ddd, 1H, J_2eq,2ax12.8 Hz, J_2eq,33.9 Hz, J_1,2eq1.9 Hz, H-

2_eq), 1.87 (m, 1H, H-3), 1.35 (ddd, 1H, J_2eq,2ax12.8 Hz, J_1,2ax9.5 Hz,

J_3,2ax1.6 Hz, H-2_ax), 1.15 (m, 1H, H-1⁰⁰b); ¹³C NMR (125 MHz, CDCl₃)

140.1, 138.7, 138.6, 138.4, 138.4, 138.3, 138.1, 138.0 (8ꢃ ipso C₆H₅);

128.3e126.6 (40ꢃ C₆H₅), 101.4 (C-1), 85.3 (C-3⁰), 79.9 (C-5⁰), 79.2

(PhCHCH₂OBn), 78.4 (C-4), 77.8 (C-5), 76.0 (C-2⁰), 75.3, 74.8 (C-4⁰,

C-1⁰), 74.9, 74.6, 74.2, 73.5, 73.3, 73.3, 73.1, 72.4 (7ꢃ PhCH₂,

PhCHCH₂OBn), 69.6 (C-6), 69.2 (C-6⁰), 36.3 (C-2), 35.9 (C-3), 34.7

(C-1⁰⁰). ESIMS: MNH₄^þ, found 1092.7. C₇₀H₇₈NO₁₀requires 1092.6.

4.1.21. Phenyl-1-thio

mannopyranosyl)methyl]-4,6-di-O-benzyl-

(30a) and phenyl-1-thio 2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-benzyl-

mannopyranosyl)methyl]-4,6-di-O-benzyl-

2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-benzyl-

a-L

-arabino-hexopyranoside

b-L

-arabino-hexopyranoside

(30b). Using the same procedure as described for the preparation of

compounds 29a,b, compound 26 (1.4 g, 1.30 mmol) was converted to

4.1.19. (S)-2-(Methoxy)-1-fenylethyl 2,3-dideoxy-3-C-[(2,3,4,6-tetra-

O-benzyl-

-mannopyranosyl)methyl]-4,6-di-O-benzyl-

-ara-

a mixture of thioglycosides 30a,b (viscous oil 1.2 g, 80%) in a ratio a/

bino-hexopyranoside (28). Using the same procedure as described

for the preparation of compound 25, aldehyde 24 (1.3 g, 1.5 mmol)

was converted to compound 28 (viscous oil, 0.9 g, 60%); [Found: C,

77.99; H, 7.04. C₇₀H₇₄O₁₀requires C, 78.19; H, 6.94%]; R_f¼0.6 (light

¼1.3:1 (integration of H-1 in ¹H NMR spectrum; for the

a anomer

d at 5.58 ppm, for the

anomer dd at 4.75 ppm); R_f¼0.4 (light pe-

troleum/ethyl acetate, 4:1). ESIMS: MNH^þ₄, found 974.8. C₆₁H₆₈NO₈S

requires 974.5. The obtained mixture was sufﬁciently pure to use in

the next step without further puriﬁcation.

petroleum/ethyl acetate, 3:1); [

]

²⁰ꢂ9.6 (c 0.85, CHCl₃); n_max3010,

2923, 2865, 1497, 1454, 1363, 1095,1028 cm^ꢂ1

;

¹H NMR (500 MHz,

CDCl₃): 7.50e7.05 (m, 40H, 8ꢃ C₆H₅), 4.94 (d, 1H, J 11.7 Hz,

OeCH₂ePh), 4.92 (dd, 1H, J 8.0, 3.7 Hz, PhCHCH₂OBn), 4.85 (d, 1H, J

10.8 Hz, OeCH₂ePh), 4.79 (dd, 1H, J_1,2ax9.5 Hz, J_1,2eq1.6 Hz, H-1),

4.1.22. Phenyl-1-thio 2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-benzyl-

mannopyranosyl)methyl]-4,6-di-O-benzyl- -arabino-hexopyrano-

side (31a) and phenyl-1-thio 2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-ben-

zyl- -mannopyranosyl)methyl]-4,6-di-O-benzyl- -arabino-hex-

b-D-

a-D

4.74e4.28 (m, 12H, 6ꢃ OeCH₂ePh), 3.95 (dd, 1H, J_{4 ,5}¼J_{3 ,4}9.5 Hz,

H-4⁰), 3.75e3.65 (m, 3H, H-6a, H-6b, PhCHCH_2aOBn), 3.65e3.58 (m,

2H, H-6⁰a, PhCHCH_2bOBn), 3.57 (br s, 1H, H-2⁰), 3.55e3.48 (m, 2H,

H-3⁰, H-6⁰b), 3.42e3.36 (m, 2H, H-1⁰, H-5⁰), 3.33 (ddd, 1H, J_4,59.4 Hz,

J_5,6b4.4 Hz, J_5,6a1.8 Hz, H-5), 3.24 (dd, 1H, J_4,5¼J_3,49.4 Hz, H-4), 2.08

(ddd, 1H, J_2eq,2ax12.8 Hz, J_2eq,34.1 Hz, J_2eq,11.6 Hz, H-2_eq), 1.82e1.66

(m, 3H, H-3, H-1⁰⁰a, H-1⁰⁰b), 1.49 (ddd, 1H, J_2ax,2eq12.8 Hz, J_2ax,312.6,

J_2ax,19.5 Hz, H-2_ax); ¹³C NMR (125 MHz, CDCl₃) 140.2, 138.7, 138.6,

138.5, 138.4, 138.4, 138.3, 138.2 (8ꢃ ipso C₆H₅), 128.4e126.8 (40ꢃ

C₆H₅), 101.7 (C-1), 85.4 (C-3⁰), 79.6 (C-5⁰), 79.4 (PhCHCH₂OBn), 78.6

(C-4), 78.5 (C-5), 77.1 (C-1⁰), 75.9 (C-2⁰), 75.5 (C-4⁰), 75.1, 74.8, 74.4,

74.3, 73.4, 73.3, 73.3, 72.6 (7ꢃ PhCH₂, PhCHCH₂OBn), 69.8 (C-6),

69.4 (C-6⁰), 38.2 (C-2), 36.9 (C-3), 33.9 (C-1⁰⁰). ESIMS: MNH^þ₄, found

1092.7. C₇₀H₇₈NO₁₀requires 1092.6.

b-D

opyranoside (31b). Using the same procedure as described for the

preparation of compounds 29a,b, compound 27 (2.9 g, 2.7 mmol)

was converted to a mixture of thioglycosides 31a,b (2.1 g, 81%), in

a ratio

¼3:1 (integration of H-1 in ¹H NMR spectrum; for the

anomer d at 5.56 ppm, for the

anomer dd at 4.67 ppm); R_f¼0.46

(light petroleum/ethyl acetate, 4:1). Repeated chromatography

afforded an analytical sample of the major -diastereoisomer 31a

as a viscous oil; [Found: C, 76.38; H, 6.89. C₆₁H₆₄O₈S requires C,

76.54; H, 6.69%]; n_max3011, 2915, 2867, 1585, 1497, 1454, 1363, 1086,

1028 cm^ꢂ1; ¹H NMR (500 MHz, CDCl₃) 7.46e7.10 (m, 35H, 7ꢃ C₆H₅),

5.58 (d, 1H, J_1,2ax5.3 Hz, H-1), 5.02 (d, 1H, J 11.6 Hz, OeCH₂ePh),

4.86 (d, 1H, J 11.6 Hz, OeCH₂ePh), 4.76e4.42 (m, 10H, 5ꢃ

OeCH₂ePh), 4.29 (m, 1H, H-5), 3.94 (dd, 1H, J_{4 ,5}¼J_{3 ,4}9.5 Hz, H-4 ),

3.81 (dd, 1H, J_{6 a,6 b}10.8 Hz, J_{6 a,5}3.6 Hz, H-6⁰a), 3.80e3.71 (m, 2H,

H-6a, H-6b), 3.69 (m, 1H, H-2⁰), 3.63 (dd, J_{6 a,6 b}10.8 Hz, 1H, J_{6 a,5}

4.1.20. Phenyl-1-thio

mannopyranosyl)methyl]-4,6-di-O-benzyl-

(29a) and phenyl-1-thio 2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-benzyl-

mannopyranosyl)methyl]-4,6-di-O-benzyl-

2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-benzyl-

1.6 Hz, H-6⁰_b), 3.53 (dd, 1H, J_{3 ,4}9.4 Hz, J_{3 ,2}2.4 Hz, H-3 ), 3.42e3.37

(m, 2H, H-1⁰, H-5⁰), 3.34 (dd, 1H, J_4,5¼J_4,39.7 Hz, H-4), 2.38e2.22 (m,

2H, H-3, H-1⁰⁰a), 2.05 (ddd, 1H, J_2eq,2ax13.8 Hz, J_2eq,33.5 Hz, J_2eq,1

w0 Hz, H-2_eq), 1.96 (ddd, 1H, J_2eq,2ax13.8 Hz, J_2ax,312.6 Hz, J_2ax,1

5.3 Hz, H-2_ax), 1.25 (m, 1H, H-1⁰⁰b); ¹³C NMR (125 MHz, CDCl₃)

138.8, 138.7, 138.5, 138.5, 138.1, 138.0, 135.6 (7ꢃ ipso C₆H₅),

130.0e126.6 (35ꢃ C₆H₅), 85.4 (C-3⁰), 84.7 (C-1), 80.0 (C-5⁰), 78.4

(C-4), 76.3 (C-2⁰), 75.4, 75.2 (C-4⁰, C-1⁰), 75.0, 74.5, 73.6, 73.5, 73.4,

72.5 (6ꢃ PhCH₂, PhCHCH₂OBn), 72.2 (C-5), 69.7 (C-6), 69.3 (C-6⁰),

36.0 (C-2), 34.2 (C-1⁰⁰), 34.1 (C-3). ESIMS: MNH^þ₄, found 974.8.

C₆₁H₆₈NO₈S requires 974.5.

a-D-arabino-hexopyranoside

a-D

b-D-arabino-hexopyranoside

(29b). BF₃$Et₂O (0.50 mL, 3.76 mmol) and thiophenol (1.3 mL,

12.5 mmol) were added in an inert atmosphere to a solution of

compound 25 (2.70 g, 2.50 mmol) in dichloromethane (150 mL) that

was pre-cooled to ꢂ78 ^ꢀC. The stirred reaction mixture was allowed to

warm spontaneously to room temperature, and after 2 h, the reaction

was quenched by cautious addition of 1 M NaOH. The reaction mix-

ture was partitioned between dichloromethane and a saturated

NaHCO₃solution, the combined organic phases were dried and

evaporated, and the residue was chromatographed on silica gel (light

petroleum/ethyl acetate, 8:1), affording 1.9 g (80%) of a mixture of

4.1.23. Phenyl-1-thio 2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-benzyl-

mannopyranosyl)methyl]-4,6-di-O-benzyl- -arabino-hexopyrano-

side (32a) and phenyl-1-thio 2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-ben-

zyl- -mannopyranosyl)methyl]-4,6-di-O-benzyl- -arabino-hex-

a-D-

thioglycosides 29a,b in a ratio

H-1 in ¹H NMR spectrum; for the

anomer dd at 4.65 ppm); R_f¼0.35 (light petroleum/ethyl acetate,

4:1). Repeated chromatography afforded an analytical sample of the

major -diastereoisomer 29a as a viscous oil; [Found: C, 76.38; H, 6.89.

C₆₁H₆₄O₈S requires C, 76.54; H, 6.69%]; n_max3011, 2913, 2868, 1585,

¼3:1 (determined by integration of

b-L

anomer d at 5.53 ppm, and for the

b-L

opyranoside (32b). Using the same procedure as described for the

preparation of compounds 29a,b, compound 28 (0.9 g, 0.84 mmol)

was converted to a mixture of thioglycosides 32a,b (viscous oil,

€

Z. Lovyova et al. / Tetrahedron 67 (2011) 4967e4979

4977

¼1.2:1 (integration of H-1 in ¹H NMR

1⁰⁰a), 0.96 (ddd, 1H, J_{1 b,1 a}13.8 Hz, J_{1 b,1}11.5 Hz, J_{1 b,3}2.6 Hz, H-

1⁰⁰b); ¹³C NMR (125 MHz, CDCl₃) 142.6 (C-1), 138.7, 138.5, 138.3,

138.3, 138.2, 137.9 (6ꢃ ipso C₆H₅), 128.5e127.4 (30ꢃ C₆H₅), 101.8 (C-

2), 77.9 (C-5⁰or C-5), 77.8 (C-3⁰), 76.6, 76.1 (C-4, C-2⁰), 75.0 (C-4⁰),

72.9 (C-5⁰or C-5), 73.9, 73.8, 73.7, 73.2, 72.1, 71.6 (6ꢃ PhCH₂), 69.8

(C-1⁰), 69.2, 68.7 (C-6, C-6⁰), 35.2 (C-3), 3.8 (C-1⁰⁰). ESIMS: MNH^þ₄,

found, 864.8. C₅₅H₆₂NO₈requires 864.4.

0.7 g, 85%), in a ratio

spectrum; for

4.71 ppm); R_f¼0.4 (light petroleum/ethyl acetate, 4:1). ESIMS:

MNH^þ₄, found 974.8. C₆₁H₆₈NO₈S requires 974.5. The obtained

mixture was sufﬁciently pure to use in the next step without fur-

ther puriﬁcation.

a/b

anomer d at 5.64 ppm, for b anomer dd at

4.1.24. 1,5-Anhydro-4,6-di-O-benzyl-2,3-dideoxy-3-C-[(2,3,4,6-tetra-

O-benzyl-

-mannopyranosyl)methyl]-

-arabino-hex-1-enitol

4.1.26. 1,5-Anhydro-4,6-di-O-benzyl-2,3-dideoxy-3-C-[(2,3,4,6-tetra-

(1). N-Bromosuccinimide (0.27 g, 1.5 mmol) was added to a solution

of anomers 29a,b (1.1 g, 1.1 mmol) in acetone (12 mL) containing 1%

water. The reaction mixture was stirred at ꢂ15 ^ꢀC under exclusion of

light, and the reaction course was monitored by TLC (light petroleum/

ethyl acetate, 3:1). After 40 min, the reaction mixture did not contain

the starting compound, and the reaction was quenched by the addi-

tion of a NaHCO₃solution to pH 8. After partitioning between

dichloromethane and aqueous NaHCO₃, the organic phase was dried,

the solventwasevaporated, andtheresiduewaschromatographed on

a short silica gel column in light petroleum/ethyl acetate (2:1),

O-benzyl-b-D-mannopyranosyl)methyl]-D-arabino-hex-1-enitol

(3). Using the same procedure as described for the preparation of

compound 1, the mixture of compounds 31a,b (1.4 g, 1.4 mmol)

was converted to compound 3 (colorless syrup, 0.87 g, 70%);

[Found: C, 77.85; H, 6.75. C₅₅H₅₈O₈requires C, 77.99; H, 6.90%];

R_f¼0.5 (light petroleum/ethyl acetate, 4:1); [

]

ꢂ5.9 (c 1.03,

CHCl₃); n_max3011, 1650, 1497, 1454, 1363, 1086, 1028, 914 cm^ꢂ1; ¹H

NMR (500 MHz, CDCl₃) 7.38e7.15 (m, 30H, 6ꢃ C₆H₅), 6.31 (dd, 1H,

J_1,26.0 Hz, J_1,32.3 Hz, H-1), 5.00 (d, 1H, J 11.7 Hz, OeCH₂ePh), 4.86

(d, 1H, J 10.9 Hz, OeCH₂ePh), 4.73e4.50 (10H, OeCH₂ePh), 4.63

affording 0.83 g of 2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-benzyl-

a-D-

(dd, 1H, J_2,16.0 Hz, J_2,31.5 Hz, H-2), 3.94 (dd, 1H, J_{4 ,3}¼J_{4 ,5}9.5 Hz,

mannopyranosyl)methyl]-4,6-di-O-benzyl- -arabino-hexopyranose

H-4⁰), 3.85e3.67 (m, 6H, H-5, H-6a, H-6b, H-6⁰a, H-6⁰b, H-2⁰), 3.54

(R_f0.3, light petroleum/ethyl acetate (2:1); ESMSI: MH^þ, found 865.7.

C₅₅H₆₁O₉requires 865.4.). The obtained compound was dissolved in

dichloromethane (20 mL), and the solution was treated in an inert

atmosphere at 0 ^ꢀC with s-collidine (1.9 mL, 14.4 mmol) and mesyl

anhydride (0.33 g,1.9 mmol). The reaction mixture was stirred at 0 ^ꢀC,

and the reaction course was monitored by TLC (light petroleum/ethyl

acetate, 3:1). After 4 h, the reaction mixture was partitioned between

dichloromethane and aqueous NaHCO₃. The organic phase was dried,

the solventwasevaporated, andtheresiduewaschromatographed on

silica gel in light petroleum/ethyl acetate (8:1), affording 0.63 g (65%)

ofcompound1asacolorlesssyrup;[Found:C,78.10;H, 6.80. C₅₅H₅₈O₈

(dd, 1H, J_{3 ,4}9.5 Hz, J_{2 ,3}2.7 Hz, H-3⁰), 3.47e3.35 (m, 3H, H-1⁰, H-4,

H-5⁰), 2.51 (m, 1H, H-3), 2.29 (ddd, 1H, J_{1 a,1 b}14.0 Hz, J 9.2 Hz, J

5.3 Hz, H-1⁰⁰a), 1.19 (ddd, 1H, J_{1 a,1 b}14.0 Hz, J 8.9 Hz, J 4.1 Hz, H-

1⁰⁰b); ¹³C NMR (125 MHz, CDCl₃) 142.6 (C-1), 138.8, 138.7, 138.5,

138.5, 138.1, 137.9 (6ꢃ ipso C₆H₅), 128.4e127.3 (30ꢃ C₆H₅), 102.6

(C-2), 85.4 (C-3⁰), 80.1 (C-5⁰), 77.9 (C-5), 76.7, 76.2, 75.3 (C-1⁰, C-4,

C-2⁰), 75.4 (C-4⁰), 75.1, 74.4, 73.8, 73.6, 73.5, 72.4 (6ꢃ PhCH₂), 69.7,

68.7 (C-6, C-6⁰), 35.6 (C-3), 35.1 (C-1⁰⁰). ESIMS: MNH^þ₄, found,

864.8. C₅₅H₆₂NO₈requires 864.4.

4.1.27. 1,5-Anhydro-4,6-di-O-benzyl-2,3-dideoxy-3-C-[(2,3,4,6-tetra-

O-benzyl-b-D-mannopyranosyl)methyl]-L-arabino-hex-1-enitol

(4). Using the same procedure as described for the preparation of

compound 1, the mixture of compounds 32a,b (0.7 g, 0.7 mmol)

was converted to compound 4 (colorless syrup, 0.43 g, 70%);

requires C, 77.99; H, 6.90%]; R_f¼0.5 (light petroleum/ethyl acetate,

4:1); [

]

ꢂ10.3 (c 1.28, CHCl₃); n_max3011, 1650, 1497, 1454, 1364,

1096, 1028, 914 cm^ꢂ1; ¹H NMR (500 MHz, CDCl₃) 7.40e7.14 (m, 30H,

6ꢃ C₆H₅); 6.24 (dd, 1H, J_1,26.0 Hz, J_1,32.3 Hz, H-1), 4.75 (dd, 1H, J_1,2

6.0 Hz, J_2,32.0 Hz, H-2); 4.73e4.44 (m,12H, OeCH₂ePh), 4.10 (ddd,1H,

[Found: C, 77.79; H, 7.10. C₅₅H₅₈O₈requires C, 77.99; H, 6.90%];

J_{1 ,1 b}8.3 Hz, J_{2 ,1}4.2 Hz, J_{1 ,1 a}4.1 Hz, H-1⁰), 3.86e3.71 (m, 6H, H-4⁰, H-

5⁰, H-5, H-6⁰a, H-6a, H-6b), 3.70e3.62 (m, 2H, H-3⁰, H-6⁰b), 3.50 (d₀d,

0 00

R_f¼0.5 (light petroleum/ethyl acetate, 4:1); [

þ10.9 (c 0.39,

CHCl₃); n_max3010, 1650, 1497, 1454, 1363, 1087, 1028, 915 cm^ꢂ1; ¹H

NMR (500 MHz, CDCl₃) 7.40e7.09 (m, 30H, 6ꢃ C₆H₅), 6.29 (dd, 1H,

J_1,25.9 Hz, J_1,32.0 Hz, H-1), 4.95 (d, 1H, J 11.7 Hz, OeCH₂ePh), 4.86

(d, 1H, J 10.9 Hz, OeCH₂ePh), 4.73 (dd, 1H, 1H, J_2,15.9 Hz, J_2,3

1.8 Hz, H-2), 4.66e4.45 (m, 10H, 5ꢃ OeCH₂ePh), 3.88 (dd, 1H,

1H, J_4,5¼J_4,38.9 Hz, H-4), 3.47 (dd, 1H, J_{2 ,1},4.2 Hz, J_{2 ,3},3.2 Hz, H-2 ),

2.33 (m, 1H, H-3), 1.67 (ddd, 1H, J_{1 a,1 b}14.2 Hz, J_{1 a,1}4.1 Hz, J_{1 a,3}

3.9 Hz, H-1⁰⁰a), 1.45 (ddd,1H, J_{1 a,1 b}14.2 Hz, J_{1 b,3}8.4 Hz, J_{1 b,1}8.3 Hz,

H-1⁰⁰b); ¹³C NMR (125 MHz, CDCl₃) 142.6 (C-1), 138.4, 138.4, 138.3,

138.3, 138.2, 137.9 (6ꢃ ipso C₆H₅),128.4e127.4 (30ꢃ C₆H₅),102.9 (C-2),

78.0, 75.0, 73.4 (C-4⁰, C-5⁰, C-5), 77.6 (C-3⁰), 76.2, 75.9 (C-2⁰, C-4), 72.6

(C-1⁰), 74.1, 73.9, 73.6, 73.3, 72.1, 71.5(6ꢃ PhCH₂), 69.3, 68.7 (C-6, C-6⁰),

38.6 (C-3), 31.8 (C-1⁰⁰). ESIMS: MNH₄^þ, found, 864.8. C₅₅H₆₂NO₈re-

quires 864.4.

J_{4 ,3}¼J_{4 ,5}9.5 Hz, H-4⁰), 3.84e3.76 (m, 3H, H-6a, H-6b, H-5), 3.73

(dd, 1H, J_{6 a,6 b}10.8 Hz, J_{6 a,5}1.8 Hz, H-6⁰a), 3.67 (dd, 1H, J_{6 a,6 b}

10.8 Hz, J_{6 b,5}5.8 Hz, H-6⁰b), 3.62 (br s, 1H, H-2⁰), 3.60e3.53 (m,

2H, H-4, H-3⁰), 3.45e3.35 (m, 2H, H-1⁰, H-5⁰), 2.39 (m, 1H, H-3),

1.83 (ddd, 1H, J_{1 a,1 b}14.1 Hz, J_{1 ,1 a}¼J_{3,1 a}8.2 Hz, H-1⁰⁰a), 1.64 (ddd,

1H, J_{1 a,1 b}14.1 Hz, J_{1 b,1}¼J_{1 b,3}3.9 Hz, H-1⁰⁰b); ¹³C NMR (125 MHz,

CDCl₃) 142.5 (C-1), 138.8, 138.8, 138.5, 138.4, 138.3, 137.9 (6ꢃ ipso

C₆H₅), 128.4e127.4 (30ꢃ C₆H₅), 103.3 (C-2), 85.3 (C-3⁰), 79.5 (C-5),

78.1 (C-5⁰), 77.5 (C-1⁰), 76.3, 76.2 (C-2⁰, C-4), 75.5 (C-4⁰), 75.1, 74.3,

74.3, 73.6, 73.4, 72.5 (6ꢃ PhCH₂), 69.9, 68.9 (C-6⁰, C-6), 38.1 (C-3),

34.1 (C-1⁰⁰). ESIMS: MNH₄^þ, found, 864.8. C₅₅H₆₂NO₈requires 864.4.

4.1.25. 1,5-Anhydro-4,6-di-O-benzyl-2,3-dideoxy-3-C-[(2,3,4,6-tetra-

O-benzyl-a-D-mannopyranosyl)methyl]-L-arabino-hex-1-enitol

(2). Using the same procedure as described for the preparation of

compound 1, the mixture of compounds 30a,b (0.8 g, 0.8 mmol)

was converted to compound 2 (colorless syrup, 0.48 g, 65%);

[Found: C, 77.75; H, 6.65. C₅₅H₅₈O₈requires C, 77.99; H, 6.90%];

R_f¼0.5 (light petroleum/ethyl acetate, 4:1); [

]

þ6.8 (c 0.45,

4.1.28. Methyl 3-deoxy-3-C-[(2,3,4,6-tetra-O-benzyl-

anosyl)methyl]-4,6-di-O-benzyl- -mannopyranoside (33) and methyl

3-deoxy-3-C-[(2,3,4,6-tetra-O-benzyl- -mannopyranosyl)methyl]-

4,6-di-O-benzyl- -glucopyranoside (34). m-Chloroperoxybenzoic

acid (77%) (150 mg, 0.67 mmol) was added, with stirring in an inert

atmosphere, to a solution of 1 (470 mg, 0.56 mmol) in anhydrous

MeOH (8 mL) and CH₂Cl₂(2 mL) at room temperature. TLC showed

that the reaction was complete after 1.5 h. The excess of peroxyacid

was reduced by addition of aqueous NaHCO₃(to pH¼8), and the

reaction mixture was partitioned between CH₂Cl₂and H₂O. The

a-D-mannopyr-

CHCl₃); n_max3009, 1651, 1496, 1454, 1363, 1096, 1028, 914 cm^ꢂ1; ¹H

NMR (500 MHz, CDCl₃) 7.39e7.14 (m, 30H, 6ꢃ C₆H₅), 6.30 (dd, 1H,

J_1,26.0 Hz, J_1,32.3 Hz, H-1), 4.74 (d, 1H, J 11.4 Hz, OeCH₂ePh), 4.66

(d, 1H, J 12.0 Hz, OeCH₂ePh), 4.62 (dd, 1H, J_1,26.0 Hz, J_2,31.8 Hz, H-

a-D

b-D

2), 4.61e4.43 (m, 10H, OeCH₂ePh), 4.09 (ddd, J_{1 ,1 b}11.5 Hz,

J_{1 ,1 a}¼J_{1 ,2}3.3 Hz, H-1⁰), 3.88 (dd, 1H, J_{4 ,3}¼J_{4 ,5}7.0 Hz, H-4⁰),

3.85e3.67 (m, 6H, H-5⁰, H-5, H-6⁰a, H-6⁰b, H-6a, H-6b), 3.63 (dd, 1H,

J_{4 ,3}7.3 Hz, J_{3 ,2}3.2 Hz, H-3 ), 3.46e3.39 (m, 2H, H-2 , H-4), 2.50 (m,

1H, H-3), 1.91 (ddd, 1H, J_{1 a,1 b}13.8 Hz, J_{1 a,3}11.1 Hz, J_{1 a,1}3.3 Hz, H-

€

Z. Lovyova et al. / Tetrahedron 67 (2011) 4967e4979

4978

organic layer was dried and concentrated, and the residue

was chromatographed on silica gel (light petroleum/ethyl acetate,

3:1) to yield 33 as a viscous oil (270 mg, 56%), R_f¼0.36 (light petro-

leum/ethyl acetate, 2:1) and 34 as a viscous oil (120 mg, 25%),

6⁰), 56.7 (OCH₃), 45.0 (C-3), 25.5 (C-1⁰⁰). ESIMS: MNH^þ₄, found 912.2.

C₅₆H₆₆NO₁₀requires 912.5.

4.1.30. Methyl 3-deoxy-3-C-[(2,3,4,6-tetra-O-acetyl-a-D-mannopyr-

R_f¼0.30 (light petroleum/ethyl acetate, 2:1). Compound 33:

anosyl)methyl]-2,4,6-tri-O-acetyl- -mannopyranoside (7). 10% Pd/

a-D

[Found: C, 74.93; H, 6.75. C₅₆H₆₂O₁₀requires C, 75.13; H, 6.93%]; [

]

C (30 mg) were added to a solution of C-disaccharide 33 (150 mg,

0.17 mmol) in MeOH (15 mL) and glacial acetic acid (3 mL), and the

reaction was stirred overnight under an atmosphere of hydrogen,

then ﬁltered through a pad of Celite and coevaporated three times

þ6.3 (c 0.92, CHCl₃); ¹H NMR (500 MHz, CDCl₃) 7.37e7.09 (m, 30H,

6ꢃ C₆H₅), 4.78e4.31 (m, 12H, OeCH₂ePh), 4.28 (br s, 1H, H-1),

4.09e4.02 (m, 2H, H-1⁰, H-2), 3.94 (dd, 1H, J_{4 ,3}¼J_{4 ,5}7.8 Hz, H-4⁰),

3.75e3.64 (m, 4H, H-5, H-6a, H-6b, H-6⁰a), 3.62 (dd, 1H, J_{3 ,4}7.8 Hz,

with toluene. The obtained compound (methyl 3-deoxy-3-C-[(

a-D-

J_{3 ,2}2.3 Hz, H-3⁰), 3.60e3.50 (m, 2H, H-5⁰, H-6⁰b), 3.50e3.40 (m, 2H,

mannopyranosyl)methyl]-

a-D

-mannopyranoside, ESIMS: MNH^þ₄,

H-4, H-2⁰), 3.31 (s, 3H, OCH₃), 1.98 (m, 1H, H-3), 1.81 (ddd, 1H, J_{1 a,1 b}

found 372.1. C₁₄H₃₀NO₁₀requires 372.2) was dissolved in pyridine

(16 mL) and Ac₂O (8 mL) and stirred overnight at room tempera-

ture. The reaction mixture was concentrated and coevaporated

three times with toluene, and column chromatography (light pe-

troleum/ethyl acetate, 2:1/1:2) yielded 55 mg (50%) of 7 as a vis-

cous oil; [Found: C, 51.60; H, 6.05. C₂₈H₄₂₀₀O₁₇requires C, 51.83; H,

14.0 Hz, J_{1 a,1}¼J_{1 a,3}11.0 Hz, H-1⁰⁰a), 1.56 (m, 1H, H-1⁰⁰b); ¹³C

NMR (125 MHz, CDCl₃) 138.3, 138.3, 138.2, 138.1, 138.1, 137.4 (6ꢃ ipso

C₆H₅), 128.4e127.5 (30ꢃ C₆H₅), 100.9 (C-1), 78.2 (C-3⁰), 77.5

(C-4), 75.7 (C-5⁰), 75.0 (C-2⁰), 74.8 (C-2), 72.6 (C-4⁰), 77.7 (C-5), 74.2,

74.1, 73.5, 73.4, 72.1, 71.7 (6ꢃ PhCH₂), 70.1, 69.7 (C-6, C-6⁰), 67.8 (C-1⁰),

54.5 (OCH₃), 42.7 (C-3), 29.7 (C-1⁰⁰). ESIMS: MNH₄^þ, found 912.2.

6.17%]; R_f¼0.67 (CHCl₃/MeOH, 15:1); [

]

þ10.7 (c 0.68, CHCl₃);

C₅₆H₆₆NO₁₀requires 912.5. Compound 34: [

]

²⁰ꢂ3.8 (c 0.85, CHCl₃);

n_max3034, 2932, 1744, 1371, 1142, 1048 cm^{ꢂ1 1}H NMR (500 MHz,

;

¹H NMR (500 MHz, CDCl₃) 7.40e7.10 (m, 30H, 6ꢃ C₆H₅), 4.68e4.43

C₆D₆) 5.56 (dd, 1H, J_{3 ,4}6.0 Hz, J_{2 ,3}3.2 Hz, H-3⁰), 5.41 (dd, 1H,

(m, 12H, 6ꢃ OeCH₂ePh), 4.22e4.17 (m, 1H, H-1⁰), 4.11 (dd, 1H, J_1,2

J_4,3¼J_4,510.5 Hz, H-4), 5.29 (dd, 1H, J_{2 ,1}6.9 Hz, J_{2 ,3}3.2 Hz, H-2⁰),

7.5 Hz, H-1), 3.98 (m, 1H, H-5⁰), 3.82 (dd, 1H, J_{3 ,4}¼J_{4 ,5}5.8 Hz, H-4⁰),

3.79e3.68 (m, 5H, H-3⁰, H-6⁰a, H-6⁰b, H-6a, H-6b), 3.57e3.52

(m, 4H, H-2⁰, OCH₃), 3.45 (m,1H, H-5), 3.35 (dd,1H, J_3,4¼J_4,59.5 Hz, H-

4), 3.21 (dd, 1H, J_2,39.6 Hz, J_1,27.5 Hz, H-2), 2.08 (m, 1H, H-1⁰⁰a),

1.80e1.67 (m, 2H, H-1⁰⁰b, H-3); ¹³C NMR (125 MHz, CDCl₃) 138.2,

138.2, 138.1, 138.1, 137.9, 137.8 (6ꢃ ipso C₆H₅), 128.3e127.4 (30ꢃ

C₆H₅), 105.4 (C-1), 77.6 (C-5), 77.2 (C-4), 76.5 (C-2⁰), 76.1 (C-3⁰), 74.6

(C-4⁰), 74.1 (PhCH₂), 73.6 (C-5⁰), 73.5 (2ꢃ PhCH₂), 73.2 (PhCH₂), 72.8

(C-2), 72.2 (PhCH₂), 71.9 (C-1⁰), 71.3 (PhCH₂), 69.1, 68.7 (C-6, C-6⁰),

56.7 (OCH₃), 46.3 (C-3), 30.7 (C-1⁰⁰). ESIMS: MNH₄^þ, found 912.2.

C₅₆H₆₆NO₁₀requires 912.5.

5.26 (dd,1H, J_2,33.0 Hz, J_2,11.3 Hz, H-2), 5.18 (dd,1H, J_{3 ,4}6.0 Hz, J_{4 ,5}

4.4 Hz, H-4⁰), 4.76 (dd,1H, J_{6 a,6 b}11.9 Hz, J_{5 ,6 a}8.0 Hz, H-6⁰a), 4.71 (d,

1H, J_2,11.3 Hz, H-1), 4.41 (dd, 1H, J_6a,6b12.1 Hz, J_5,6a5.2 Hz, H-6a),

4.21e4.12 (m, 2H, H-1⁰, H-6b) 4.06 (ddd,1H, J_{5 ,6 a}8.0 Hz, J_{5 ,4}4.4 Hz,

J_{5 ,6 b}3.7 Hz, H-5⁰), 4.02 (dd, 1H, J_{6 a,6 b}11.9 Hz, J_{5 ,6 b}3.7 Hz, H-6⁰b),

3.89 (ddd, 1H, J_5,410.5 Hz, J_5,6a5.2 Hz, J_5,6b2.5 Hz, H-5), 3.0 (s, 3H,

OCH₃), 2.58 (dddd, 1H, J_4,310.5 Hz, J_{1 a,3}¼J_{1 b,3}5.5 Hz, J_3,23.0 Hz, H-

3),1.87 (s, 3H, COOCH₃),1.86e1.84 (m, 2H, H-1⁰⁰a, H-1⁰⁰b),1.82 (s, 3H,

COOCH₃), 1.75 (s, 3H, COOCH₃), 1.71 (s, 3H, COOCH₃), 1.65 (s, 3H,

COOCH₃), 1.57 (s, 3H, COOCH₃), 1.53 (s, 3H, COOCH₃); ¹³C NMR

(125 MHz, C₆D₆) 170.1e169.1 (7ꢃ COOCH₃), 97.8 (C-1), 73.0 (C-5⁰),

72.4 (C-2), 71.0 (C-1⁰), 70.3 (C-2⁰), 69.6 (C-5), 68.6 (C-4), 68.2 (C-4⁰),

68.1 (C-3⁰), 63.1 (C-6), 60.9 (C-6⁰), 54.5 (OCH₃), 37.1 (C-3), 29.1

(C-1⁰⁰), 20.4e20.1 (7ꢃ COOCH₃). ESIMS: MNH^þ₄, found 665.9.

C₂₈H₄₄NO₁₇requires 666.2.

4.1.29. Methyl 3-deoxy-3-C-[(2,3,4,6-tetra-O-benzyl-

anosyl)methyl]-4,6-di-O-benzyl- -mannopyranoside (35) and

methyl 3-deoxy-3-C-[(2,3,4,6-tetra-O-benzyl- -mannopyranosyl)

methyl]-4,6-di-O-benzyl- -glucopyranoside (36). Using the same

a-D-mannopyr-

a-L

a-D

b-L

procedure as in the previous case, the glucal 2 (290 mg, 0.34 mmol)

was converted to compounds 35 (viscous oil, 160 mg, 51%), R_f¼0.30

(light petroleum/ethyl acetate, 2:1) and 36 (viscous oil, 76 mg, 24%),

R_f¼0.36 (light petroleum/ethyl acetate, 2:1). Compound 35:

[Found: C, 74.93; H, 6.75. C₅₆H₆₂O₁₀requires C, 75.13; H, 6.93%];

4.1.31. Methyl 3-deoxy-3-C-[(2,3,4,6-tetra-O-acetyl-

a-D-mannopyr-

anosyl)methyl]-2,4,6-tri-O-acetyl- -mannopyranoside (8). Using

a-L

the same procedure as for the preparation of 7, compound 35

(160 mg, 0.18 mmol) was converted to C-disaccharide 8 (viscous oil,

80 mg, 67%); [Found: C, 51.55; H, 6.35. C₂₈H₄₀O₁₇requires C, 51.83;

[

²⁰ꢂ4.2 (c 0.56, CHCl₃); ¹H NMR (500 MHz, CDCl₃) 7.40e7.10 (m,

H, 6.17%]; R_f¼0.67 (CHCl₃/MeOH, 15:1); [

]

ꢂ6.9 (c 0.75, CHCl₃);

30H, 6ꢃ C₆H₅), 4.69 (d, 1H, J 11.4 Hz, OeCH₂ePh), 4.65 (d, 1H, J

11.4 Hz, OeCH₂ePh), 4.59 (br s, 1H, H-1), 4.57e4.34 (m, 10H,

OeCH₂ePh), 4.19 (m, 1H, H-1⁰), 3.87e3.82 (m, 2H, H-2, H-6a),

3.81e3.65 (m, 7H, H-5, H-3⁰, H-4⁰, H-5⁰, H-6b, H-6⁰a, H-6⁰b),

3.58e3.53 (m, 2H, H-2⁰, H-4), 3.3 (s, 3H, OCH₃), 2.19 (m, 1H, H-3),

1.93 (m, 1H, H-1⁰⁰a), 1.64 (m, 1H, H-1⁰⁰b); ¹³C NMR (125 MHz, CDCl₃)

138.5e138.1 (6ꢃ ipso C₆H₅), 128.3e127.3 (30ꢃ C₆H₅), 100.6 (C-1),

76.7 (C-3⁰), 76.1, 74.9, 73.8 (C-4, C-2⁰, C-2), 74.1, 73.5, 73.5, 73.2, 72.1,

71.5 (6ꢃ PhCH₂), 73.3, 72.0, 69.3 (C-4⁰, C-5, C-4⁰), 69.4, 69.0 (C-6, C-

n_max3011, 1671, 1625, 1454, 1390, 1094, 1028 cm^{ꢂ1 1}H NMR

;

(500 MHz, C₆D₆) 5.57 (dd, 1H, J_{3 ,4}6.1 Hz, J_{3 ,2}3.2 Hz, H-3 ), 5.37 (br

s, 1H, H-2), 5.30 (dd, 1H, J_4,₀₃11.2 Hz, J_4,510.5 Hz, H-4), 5.27 (dd, 1H,

J_{2 ,1}6.2 Hz, J_{2 ,3}3.2 Hz, H-2 ), 5.17 (dd, 1H, J_{4 ,3}6.1 Hz, J_{4 ,5}5.0 Hz, H-

4⁰), 4.60 (br s, 1H, H-1), 4.61 (dd, 1H, J_{6 a,6 b}12.1 Hz, J_{5 ,6 a}8.7 Hz, H-

6⁰a), 4.35 (dd, 1H, J_6a,6b12.2 Hz, J_5,6a5.3 Hz, H-6a), 4.25 (dd, 1H,

J_{6 a,6 b}12.1 Hz, J_{5 ,6 b}3.4 Hz, H-6⁰b), 4.22e4.10 (m, 3H, H-1⁰, H-5⁰, H-

6b), 3.88 (m, 1H, H-5), 2.98 (s, 3H, OCH₃), 2.73 (dddd, 1H, J_3,4¼J_{3,1 a}

11.2 Hz, J_{3,1 b}¼J_3,23 Hz, H-3), 1.92 (m, 1H, H-1⁰⁰a), 1.87 (s, 3H,

6⁰), 54.7 (OCH₃), 37.9 (C-3), 26.5 (C-1⁰⁰). ESIMS: MNH^þ, found 912.2.

COOCH₃), 1.78 (m, 1H, H-1⁰⁰b), 1.74 (s, 3H, COOCH₃), 1.73 (s, 3H,

COOCH₃), 1.68 (s, 3H, COOCH₃), 1.66 (s, 3H, COOCH₃), 1.61 (s, 3H,

COOCH₃), 1.58 (s, 3H, COOCH₃); ¹³C NMR (125 MHz, C₆D₆)

170.1e169.3 (7ꢃ COOCH₃), 98.2 (C-1), 72.7 (C-5⁰), 70.5 (C-2⁰), 69.4,

69.3 (C-2, C-5), 68.6 (C-4⁰), 68.1 (C-3⁰), 67.9 (C-4), 67.3 (C-1⁰), 63.2

(C-6), 61.4 (C-6⁰), 54.4 (OCH₃), 35.1 (C-3), 27.0 (C-1⁰⁰), 20.3e20.1 (7ꢃ

COOCH₃). ESIMS: MNH₄^þ, found 665.9. C₂₈H₄₄NO₁₇requires 666.2.

C₅₆H₆₆NO₁₀requires 912.5. Compound 36: [

⁴þ5.6 (c 0.56,

CHCl₃); ¹H NMR (500 MHz, CDCl₃) 7.40e7.14 (m, 30H, 6ꢃ C₆H₅),

0 00

4.73e4.39 (m, 11H, OeCH₂ePh), 4.33 (ddd, 1H, J_{1 ,1 b}10.4 Hz, J_{1 ,1 a}

3.9 Hz, J_{1 ,2}2.2 Hz, H-1 ), 4.23 (d, 1H, 1H, J 11.0 Hz, OeCH₂ePh), 4.10

(d, 1H, J_1,27.7 Hz, H-1), 3.94 (ddd, 1H, J_{5 ,4}¼J_{5 ,6 a}7.4 Hz, J_{5 ,6 b}2.8 Hz,

H-5⁰), 3.77e3.65 (m, 5H, H-3⁰, H-4⁰, H-6a, H-6b, H-6⁰a), 3.63e3.56

(m, 2H, H-6⁰b, H-2), 3.53e3.48 (m, 4H, H-2⁰, OCH₃), 3.45 (ddd, 1H,

J_4,59.6 Hz, J_5,6a¼J_5,6b3.3 Hz, H-5), 3.38 (dd, 1H, J_4,310.5 Hz, J_4,5

9.6 Hz, H-4), 2.16 (m, 1H, H-1⁰⁰a), 1.84 (m, 1H, H-3), 1.56 (m, 1H, H-

1⁰⁰b); ¹³C NMR (125 MHz, CDCl₃) 138.1e137.8 (6ꢃ ipso C₆H₅),

128.3e127.5 (30ꢃC₆H₅), 105.6 (C-1), 77.8, 77.7 (C-5, C-3⁰), 76.4 (C-

2⁰), 75.3 (C-4⁰), 74.9 (C-4), 73.9, 73.8, 73.5, 73.3 (4ꢃ PhCH₂), 72.8 (C-

5⁰), 72.3, 71.6 (2ꢃ PhCH₂), 71.2 (C-2), 71.0 (C-1⁰), 69.6, 69.2 (C-6, C-

Acknowledgements

This work was supported by the Grant Agency of the Czech

Republic (Grant No. 203/08/1124) and by the Ministry of Education,

Youth and Sport of the Czech Republic (Grant No. 6046137305).

€

Z. Lovyova et al. / Tetrahedron 67 (2011) 4967e4979

4979

8. Liu, J.; Gin, D. Y. Tetrahedron Lett. 2003, 44, 4015e4018.

Supplementary data

9. (a) Parrish, J. D.; Little, R. D. Org. Lett. 2002, 4, 1439e1442; (b) Allwein, S. P.; Cox,

J. M.; Howard, B. E.; Johnson, H. W. B.; Rainier, J. D. Tetrahedron 2002, 58,

1997e2009; (c) Codee, J. D. C.; van der Marel, G. A.; van Boeckel, C. A. A.; van

Boom, J. H. Eur. J. Org. Chem. 2002, 3954e3965.

Supplementary data associated with this article can be found in

the online version, at doi:10.1016/j.tet.2011.04.044. These data in-

clude MOL ﬁle and InChIKey of the most important compounds

described in this article.

€

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