Regioselective synthesis of 6-alkynyl-6-deoxy and pseudo-C- disaccharides derivatives of mannofuranose via a 5,6-cyclic sulfate

Article abstract of DOI:10.1055/s-1999-3389

C-6 opening of a 5,6-cyclic sulfate derivative of mannofuranoside 1 with acetylenic anion generated from oct-1-yne or phenylethyne gave corresponding 6-alkynyl-6-deoxy derivatives 2 and 3 respectively. The reaction of 5,6- cyclic sulfate 1 with lithium acetylide derived from monosaccharide led to pseudo-C-disaccharide 5. A one-pot procedure was achieved using lithium acetylide in THF/HMPA, to prepare symmetric pseudo-C-disaccharide 7. This method, used with a 5,6-cyclic sulfate derivative of glucofuranose 11 with the acetylide anion derived from mannofuranose 9, gave the corresponding nonsymmetric pseudo-C-disaccharide 13.

Full text of DOI:10.1055/s-1999-3389

290
PAPER
Regioselective Synthesis of 6-Alkynyl-6-Deoxy and Pseudo-C-Disaccharides
Derivatives of Mannofuranose via a 5,6-Cyclic Sulfate
Thierry Gourlain, Anne Wadouachi, Daniel Beaup•re*
Laboratoire de Chimie Organique, UniversitŽ de Picardie Jules Verne, 33 rue Saint-Leu F- 80039 Amiens, France
Fax +33(3)22827562; E-mail: daniel.Beaup•re@sc.u-picardie.fr
Received 11 May 1998
in probing the spatial relationship of appendant sugars has
Abstract: C-6 opening of a 5,6-cyclic sulfate derivative of manno-
also been described in the relationship to the generation of
furanoside 1 with acetylenic anion generated from oct-1-yne or
antiviral agents which require polydentate interactions.11
phenylethyne gave corresponding 6-alkynyl-6-deoxy derivatives 2
and 3 respectively. The reaction of 5,6-cyclic sulfate 1 with lithium
Most examples of alkynyl substituted C-disaccharides re-
acetylide derived from monosaccharide led to pseudo-C-disaccha-
ported in the literature are synthesized by reaction of a
ride 5. A one-pot procedure was achieved using lithium acetylide in
glyconolactone with the in situ generated acetylenic anion
derived from a monosaccharide.12 For example, the syn-
thesis of trans-fused dipyranyl sugars containing an acet-
ylenic moiety at C-1 has been completed starting from D-
glucose. 13
THF/HMPA, to prepare symmetric pseudo-C-disaccharide 7. This
method, used with a 5,6-cyclic sulfate derivative of glucofuranose
11 with the acetylide anion derived from mannofuranose 9, gave the
corresponding nonsymmetric pseudo-C-disaccharide 13.
Key words: cyclic sulfate, monosaccharides, alkynes, 6-alkynyl
sugars, pseudo-C-disaccharides
Herein we report the reaction of methyl 2,3-O-isopropyl-
idene-5,6-O-sulfuryl-a-D-mannofuranoside (1) with phe-
nylethynyl and octynyllithium, sodium acetylide and
lithium acetylide of manno and glucofuranose derivatives.
Electrophilic activation of vicinal diols towards the addi-
tion of carbon nucleophiles may be accomplished by di-
rect conversion into a cyclic sulfate. The use of carbon
nucleophiles such as phenyllithium,1 cyanide,2 benzyl-
magnesium bromide (Li2CuCl4 catalyzed),3 malonate,3 a-
dithiaaryl carboxylate anions,4 2-dithianyllithium spe-
cies,4 (2-phenylsulfanyl)-2-dihydropyranyllithium spe-
cies,5 enolates of esters and amides,6 a-sulfonyl, a-cyano
and a-phosphonyl substituted anions,6 dibromo-
methyllithium7 allowed regiospecific ring opening of a
cyclic sulfate and generated a secondary alcohol function
on workup with diluted acid. Only two examples of nu-
cleophilic displacement reactions of cyclic sulfate by
acetylenic anions are described in the literature. The reac-
tion of ethylene sulfate with phenylethynyllithium ion
gave the corresponding b-substituted ethyl sulfate in
quantitative yield.1 In the first synthesis of valilactone,8 a
potent esterase inhibitor, the first step was performed by
reaction of an acetylenic anion generated from 1-trimeth-
ylsilyloct-3-en-1-yne with 1,2-O-sulfurylheptane to give
the corresponding coupled product in 63% yield.
5,6-Cyclic sulfate derivative 1 easily reacted with phenyl-
acetylene and oct-1-yne in the presence of butyllithium in
THF to give methyl 6,7,8-trideoxy-2,3-O-isopropylidene-
8-phenyl-a-D-manno-oct-7-ynofuranoside (2) and methyl
6,7,8-trideoxy-8-hexyl-2,3-O-isopropylidene-a-D-man-
no-oct-7-ynofuranoside (3) in 93% and 86% yield respec-
tively after acidic hydrolysis of the acyclic sulfate at the
C-5 atom (Scheme 1).
Then, we prepared the pseudo-C-disaccharide 5 by reac-
tion of the lithium acetylide derived from monosaccharide
4
12c,14 with the 5,6-cyclic sulfate 1, in 74% yield. To pre-
pare a symmetric pseudo-C-disaccharide, our initial at-
tempt was focused on the sequential generation of the
alkylidene dianions in the reaction of sodium acetylide
with 2.1 equivalents of 5,6-cyclic sulfate derivative 1 in
THF/HMPA (95:5). The reaction was unsuccessful and
led to a complex mixture of products.
On the other hand, the use of 3 equivalents of sodium
acetylide with 5,6-cyclic sulfate 1 in DMF at Ð5¡C for
35 min provided the monomer 6 in 71% yield. Unexpect-
edly, the same reaction was achieved in THF/HMPA
(95:5) at room temperature and gave a mixture of com-
pound 6 and 7 in a 3/7 ratio in 72% yield.
We have previously reported the regioselective synthesis
of 6-O-alkyl derivatives of mannofuranose and ether
linked pseudo-di or trisaccharides derived from manno
and glucofuranose via a 5,6-cyclic sulfate.9,10
The isolated compound 6 reacted with 2 equivalents of
butyllithium and 5,6-cyclic sulfate 1 to only give the pseu-
do-disaccharide 8 connected by an ether linkage. So it was
first necessary to protect the 5-OH hydroxyl group by a si-
lyl ether (TBDPS). Then the nucleophilic opening of the
5,6-cyclic sulfate 1 by the anion derived from 9 provided
pseudo-C-disaccharide 7 in 61% yield after deprotection
of the silyl ether. The compound 7 was only obtained in
Now, our interest was to synthesize methyl 6-alkynyl-6-
deoxymannofuranoside and pseudo-C-disaccharide deriv-
atives containing an acetylenic moiety from mannose and
glucose derivatives. The C-oligosaccharides have been in-
vestigated as readily accessible substrates for the intro-
duction groups with fixed distance relationship to one
another. The use of these compounds as rigid frameworks
Synthesis 1999, No. 2, 290–294 ISSN 0039-7881 © Thieme Stuttgart á New York

PAPER
Regioselective Synthesis of Derivatives of Mannofuranose
291
Scheme 1
performed using 230Ð400 mesh Merck silica gel. Optical rotations
were determined with a Jasco-DIP-370 electronic micropolarime-
ter. NMR spectra were recorded in CDCl3, on a Bruker 300 WB
spectrometer. Chemical shifts are expressed in ppm downfield from
TMS. Coupling constants, assigned by double irradiation, are in Hz
and splitting pattern abbreviations are: s, singlet; d, doublet; m,
multiplet; t, triplet; q, quadruplet. Elemental analysis were per-
formed by the ÒService Central de Microanalyse du CNRSÓ of Ver-
naison (69-Rh™ne-France). All solvents were distilled before use.
THF was distilled from LiAlH4, thionyl chloride from triphe-
nylphosphite (10 % V/V). All reactions were performed under Ar.
32% overall yield from the cyclic sulfate 1 in four steps.
Compound 7 was isolated in 50% yield from 1 following
the one step reaction in THF/HMPA as described above.
To obtain nonsymmetric pseudo-C-disaccharides, the acetyl-
ide anion derived from the compound 9 could react with oth-
er cyclic sulfate derivatives of monosaccharides (Scheme 2).
So, the reaction of 5,6-cyclic sulfate glucofuranose deriv-
ative 1115 with the anion derived from 9 afforded the pseu-
do-C-disaccharides 13 in 63% yield.
Methyl 6,7,8-Trideoxy-2,3-O-isopropylidene-8-phenyl-α-D-
manno-oct-7-ynofuranoside (2)
The procedure described herein constitutes a very conve-
nient method for the synthesis of 6-C-alkynyl-6-deoxy-
monosaccharides and symmetric or nonsymmetric
pseudo-C-disaccharide derivatives from a 5,6-cyclic sul-
fate derived from manno and glucofuranose.
To a solution of phenylacetylene (0.143 mL, 1.26 mmol) in THF
(4.2 mL) cooled to Ð5¡C under Ar was added dropwise a solution
of BuLi (0.506 mL of 2.5 M solution in THF, 1.26 mmol). After
stirring at Ð5¡C for 2 h, compound 1 ( 250 mg, 0.844 mmol) was
added. After 2 h at Ð5¡C, H2SO4 (40 mL) and H2O (20 mL) were add-
ed, the mixture was stirred for 10 min at r.t. and poured into a cold
molar solution of NaHCO3 (10 mL). The aqueous solution was ex-
tracted with EtOAc and the combined extracts were dried (Na2SO4)
and concentrated under reduced pressure. The residue was chro-
matographed on silica gel (85:15 hexaneÐEtOAc) to yield 2 (249
mg, 93%) as a colorless syrup. Rf 0.40 (6:4 hexaneÐEtOAc); [a]D27
+71.6 (c = 0.32, CH2Cl2).
1H NMR (CDCl3): d = 7.36 (m, 2H, CH(Ph)), 7.22 (m, 3H,
Scheme 2
CH(Ph)), 4.87 (s, 1H, H-1), 4.83 (dd, 1H, H-3, J2Ð3 = 5.9 Hz, J3Ð4
=
3.6 Hz), 4.53 (d, 1H, H-2), 4.12 (m, 1H, H-5), 3.96 (dd, 1H, H-4,
J4Ð5 = 8.0 Hz), 3.27 (s, 3H, CH3O), 2.85 (dd, 1H, H-6, J5Ð6 = 4.5 Hz,
J6Ð6' = 17 Hz), 2.74 (dd, 1H, H-6', J5Ð6' = 6.2 Hz), 1.43, 1.27 (2s, 6H,
C(CH3)2).
Melting points were determined with a Buchi 535 apparatus and are
uncorrected. TLC was performed on silica gel Merck 60 F254 plates
with visualization by UV light (254 nm) and/or by charring with a
vanillinÐH2SO4 reagent. Preparative column chromatography was
Synthesis 1999, No. 2, 290–294 ISSN 0039-7881 © Thieme Stuttgart · New York

292
T. Gourlain et al.
PAPER
13C NMR (CDCl3): d = 131.6, 128.1, 127.8 (CH(Ph)), 123.4 (Cipso),
112.6 (C(CH3)2), 106.9 (C-1), 85.6, 82.8 (C-7, C-8), 84.9 (C-2),
80.5 (C-4), 79.8 (C-3), 68.0 (C-5), 54.3 (OCH3), 25.9 (C(CH3)2),
25.5 (C-6), 24.6 (C(CH3)2).
duced pressure and the residue was diluted by 2 mL of THF. H2SO4
(40 mL) and H2O (20 mL) were added dropwise and the mixture was
stirred for 20 min at r.t.. A cold molar solution of NaHCO3 (10 mL)
was added and the mixture was treated as described above for 2 (8:2
hexaneÐEtOAc, silica gel chromatographed) to give 6 (14.3 mg,
C18H22O5
(318.36)
calcd
C
C
67.91
68.07
H
H
6.96
6.78
70%) as a pale yellow syrup. Rf 0.40 (6:4 hexaneÐEtOAc); [a]25
D
found
+71.7 (c = 0.44, CH2Cl2).
1H NMR (CDCl3): d = 4.84 (s, 1H, H-1); 4.79 (dd, 1H, H-3, J2Ð3
=
Methyl 6,7,8-Trideoxy-8-hexyl-2,3-O-isopropylidene-α-D-man-
no-oct-7-ynofuranoside (3)
Oct-1-yne (0,186 mL,1.26 mmol) was treated as described above
for 2 to yield 3 (237 mg, 86%) as a colorless syrup. Rf 0.45 (6:4 hex-
aneÐEtOAc); [a]D27 +51.1 (c = 0.23, CH2Cl2).
5.9 Hz, J3Ð4 = 3.7 Hz), 4.52 (d, 1H, H-2), 4.02 (m, 1H, H-5), 3.90
(dd, 1H, H-4, J4Ð5 = 8.0 Hz), 3.26 (s, 3H, CH3O), 2.70 (m, 1H, OH),
2.62 (dq, 1H, H-6, J5Ð6 = 4.5 Hz, J6Ð6' = 16.9 Hz, J6Ð8 = 2.7 Hz), 2.51
(dq, 1H, H-6', J5Ð6' = 6.3 Hz, J6'Ð8 = 2.7 Hz), 2.01 (t, 1H, H-8), 1.41,
1.27 (2s, 6H, C(CH3)2).
13C NMR (CDCl3): d = 112.6 (C(CH3)2), 106.8 (C-1), 84.8 (C-2),
80.3 (C-4), 80.2 (C-7), 79.7 (C-3), 70.7 (C-8), 67.8 (C-5), 54.4
(OCH3), 25.9, 24.5 (C(CH3)2), 24.4 (C-6).
1H NMR (CDCl3): d = 4.78 (s, 1H, H-1), 4.74 (dd, 1H, H-3, J2Ð3
=
5.9 Hz, J3Ð4 = 3.5 Hz), 4.46 (d, 1H, H-2), 3.93 (m, 1H, H-5), 3.82
(dd, 1H, H-4, J4Ð5 = 8.0 Hz), 3.21 (s, 3H, CH3O), 2.53 (dq, 1H, H-
6, J5Ð6 = 4.6 Hz, J6Ð6' = 16.7 Hz, J6Ð9,9' = 2.3 Hz), 2.42 (ds, 1H, H-6',
J5Ð6' = 5.9 Hz, J6'Ð9 = 2.5 Hz, J6'Ð9' = 2.3 Hz), 2.06 (m, 2H, H-9, H-
9'), 1.39, 1.24 (2s, 6H, C(CH3)2), 1.43Ð1.15 (m, 8H, CH2 10Ð13), 0.78
(t, 3H, H-14, H-14',H-14'').
13C NMR (CDCl3): d = 111.5 (C(CH3)2), 105.9 (C-1), 83.9 (C-2),
82.1 (C-7), 79.4 (C-4), 78.8 (C-3), 74.3 (C-8), 67.0 (C-5), 53.2
(OCH3), 30.3 (C-12), 27.9, 27.5, 21.5 (C-10, C-11, C-13), 24.9
(C(CH3)2), 23.8 (C-6), 23.6 (C(CH3)2), 17.7 (C-9), 12.9 (C-14).
IR (NaCl): n = 3287 (C C-H), 3481 cmÐ1 (O-H)
C12H18O5
(242.27)
calcd
C
C
59.49
59.61
H
H
7.79
7.71
found
Bis(methyl 6-deoxy-2,3-O-isopropylidene-α-D-manno-fura-
nosid-6-yl)acetylene (7)
To a solution of sodium acetylide (1.1 g of 18% W solution in xy-
lene, 2.53 mmol) was added dropwise a solution of compound 1
(250 mg, 0.844 mmol) in THF (2.1 mL) and HMPA (0.105 mL) at
r.t.. The mixture was stirred for 3 h. H2SO4 and H2O (40 mLÐ20 mL)
were added to the mixture at r.t.. After 20 min, the reaction was
poured into a cold molar solution of NaHCO3 (10 mL). The aqueous
solution was extracted with EtOAc and the combined extracts were
dried (Na2SO4) and concentrated in vacuo. The residue was chro-
matographed on silica gel (8:2 then 6:4 hexaneÐEtOAc) to yield 7
(189 mg, 50%) and the monomer 6 (43 mg, 21%). Rf 0.15 (6:4 hex-
aneÐEtOAc).
1H NMR (CDCl3): d = 4.84 (s, 2H, H-1, H-1'), 4.79 (dd, 2H, H-3,
H-3', J2-3, 2'-3' = 5.9 Hz, J3-4, 3'-4' = 3.6 Hz), 4.51 (d, 2H, H-2, H-2'),
4.00 (m, 2H, H-5, H-5'), 3.87 (dd, 2H, H-4, H-4', J4Ð5, 4'Ð5' = 8.0 Hz),
3.26 (s, 6H, CH3O), 2.61 (dd, 2H, H-6a, H-6a', J5aÐ6a, 5a'Ð6a' = 3.4 Hz,
J6aÐ6b, 6a'Ð6b' = 14.7 Hz), 2.48 (dd, 2H, H-6b, H6b', J5aÐ6b, 5a'Ð6b'
5.2 Hz), 1.42, 1.27 (2s, 12H, C(CH3)2).
C18H30O5
(326.43)
calcd
C
C
66.23
66.06
H
H
9.26
9.34
found
Methyl 6,7,8-Trideoxy-2,3-O-isopropylidene-8-(2,3,4,6-tetra-O-
benzyl-6-deoxy-α-D-glucopyranos-1-yl)-α-D-manno-oct-7-yno-
furanoside (5)
To a solution of (2,3,4,6-tetra-O-benzyl-b-D-glucopyranosyl)oc-
tyne 4 (149 mg, 0.27 mmol) in THF (0.7 mL) cooled to Ð40¡C was
added BuLi (119 mL of 2.5 M solution in THF, 0.30 mmol). After
stirring at r.t. for 4 h, the mixture was cooled to Ð40¡C and com-
pound 1 (96.5 mg, 0.32 mmol) and HMPA (70 mL) were added. The
mixture was stirred for 2 h at Ð40¡C and was treated as described
above for compound 2 (H2SO4 17 mL, H2O 6 mL, 2 h, r.t.) chroma-
tography on silica gel (8:2 hexaneÐEtOAc) gave 5 (154 mg, 74%)
as a colorless syrup. Rf:0.30 (7:3 hexaneÐEtOAc); [a]D28 +18.2 (c =
0.7, CH2Cl2).
=
13C NMR (CDCl3): d = 112.6 (C(CH3)2), 106.9 (C-1, C-1'), 84.8 (C-
2, C-2'), 80.5 (C-4, C-4'), 79.8 (C-3, C-3'), 78.5 (C-7, C-7'), 68.1 (C-
5, C-5'), 54.4 (OCH3), 25.9 (C(CH3)2), 24.8 (C-6, C-6'), 24.6
(C(CH3)2).
1H NMR (CDCl3): d = 7.26 (m, 24H), 5.08Ð4.92 (dd, 2H, CH2(Ph)),
4.89 (s, 1H, H-1), 4.83 (dd, 2H, CH2(Ph)), 4.73 (dd, 1H, H-3, J2Ð3
=
5.9 Hz, J3Ð4 = 3.65 Hz), 4.53 (m, 4H, CH2(Ph)), 4.11 (m, 2H, H-5,
H-1'), 3.94 (dd, 1H, H-4, J4Ð5 = 7.7 Hz), 3.93 (m, 2H, H-6'', H-6'''),
3.62 (m, 3H, H-2', H-3', H-4'), 3.44 (m, 1H, H-5'), 3.28 (s, 3H,
CH3O), 2.75 (dq, 1H, H-6, J5Ð6 = 4.5 Hz, J6Ð6' = 16.9 Hz, J6Ð8 = 1.8
Hz), 2.62 (dq, 1H, H-6', J5Ð6' = 6.8 Hz, J6'Ð8 = 1.75 Hz), 1.45, 1.30
(2s, 6H, C(CH3)2).
13C NMR (CDCl3): d = 138.5, 138.2, 138.1 (4Cipso), 128.4, 127.9,
128.0, 127.8 (CH(Ph)), 112.6 (C(CH3)2), 107.0 (C-1), 86.0, 82.4,
77.7 (C-2', C-3', C-4'), 82.9, 79.6 (C-7, C-7'), 80.6 (C-4), 79.8 (C-
3), 78.9 (C-5'), 75.7, 75.3, 75.0, 73.5 (CH2(Ph)), 70.1 (C-1'), 68.8
(C-6'), 68.2 (C-5), 54.5 (OCH3), 26.0 (C(CH3)2), 25.1 (C-6), 24.6
(C(CH3)2).
C22H34O10
(458.50)
calcd
C
C
57.63
57.73
H
H
7.47
7.37
found
Methyl 6,7,8-Trideoxy-2,3-O-isopropylidene-5-O-(methyl 6-
deoxy-2,3-O-isopropylidene-α-D-manno-furanosid-6-yl)-α-D-
manno-oct-7-ynofuranoside (8)
Compound 6 (72.4 mg, 0.3 mmol) was treated by two equivalents
of BuLi (0.245 mL of 2.5 M solution in THF, 0.614 mmol) in DMF
(2 mL) cooled to Ð5¡C under Ar for 2 h. Compound 1 (136.8 mg,
0.48 mmol) was added at Ð5¡C and the mixture stirred to r.t.. After
15 min TLC show the total conversion of all starting material in a
single spot on base line. After concentration under reduced pres-
sure, the residue was dissolved in THF (3 mL) and treated as de-
scribed above for 2 to yield 8 (95 mg, 69%) as a colorless syrup. Rf
0.8 (1:1 hexaneÐEtOAc); [a]D25+ 55.1 (c = 0.85, CH2Cl2).
1H NMR (CDCl3): d = 4.76 (m, 3H, H-1, H-1', H-3), 4.72 (dd, 1H,
H-3', J2'Ð3' = 5.9 Hz, J3'Ð4' = 3.8 Hz), 4.45 (m, 2H, H-2, H-2'), 4.10
(m, 2H, H-5, H-5'), 3.95 (dd, 1H, H-4, J3Ð4 = 3.6 Hz, J4Ð5 = 9.1 Hz),
3.71 (m, 2H, H-4', H-6''), 3.43 (dd, 1H, H-6''', J6''Ð6''' = 10.5 Hz,
C46H52O10
(764.91)
calcd
C
C
72.23
72.06
H
H
6.85
6.97
found
Methyl 6,7,8-Trideoxy-2,3-O-isopropylidene-α-D-manno-oct-7-
ynofuranoside (6)
A solution of sodium acetylide (1.1 g of 18% W solution in xylene,
2.53 mmol) was added dropwise to a solution of compound 1
(250 mg, 0.844 mmol) in DMF (2.1 mL) cooled to Ð5¡C under Ar.
After 35 min all of starting material had disappeared to give a single
spot on baseline in TLC. The mixture was concentrated under re-
J6'''Ð5' = 8.1 Hz), 3.20, 3.19 (2s, 6H, CH3O), 2.71 (dt, 1H, H-6, J5Ð6
=
Synthesis 1999, No. 2, 290–294 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Regioselective Synthesis of Derivatives of Mannofuranose
293
5.8 Hz, J6Ð6' = 17.3 Hz, J6Ð8 = 2.7 Hz), 2.46 (dq, 1H, H-6', J5Ð6'
4.6 Hz, J6'Ð8 = 2.7 Hz), 1.93 (t, 1H, H-8), 1.36, 1.35, 1.23, 1.21 (4s,
12H, C(CH3)2).
=
C38H52O10Si calcd
(696.90) found
C
C
65.50
65.68
H
H
7.52
7.59
13C NMR (CDCl3): d = 112.4 (2C(CH3)2), 107.2, 106.6 (C-1, C-1'),
84.6, 84.5 (C-2, C-2'), 80.2 (C-7), 79.8 (C-4), 79.5 (C-3'), 79.2 (C-
3, C-4'), 75.9 (C-5), 72.9 (C-6'), 70.3 (C-8), 68.4 (C-5'), 54.3, 54.2
(OCH3), 25.8, 25.6, 24.7, 24.6 (C(CH3)2), 21.3 (C-6').
6,7,8-Trideoxy-3-O-benzyl-1,2-O-isopropylidene-8-(methyl 5-
O-tert-butyldiphenylsilyl-6-deoxy-2,3-O-isopropylidene-α-D-
manno-furanosid-6-yl)-α-D-gluco-oct-7-ynofuranoside (12)
9 was treated as described above for 6 with 3-O-benzyl-1,2-O-iso-
propylidene-5,6-O-sulfuryl-a-D-glucofuranose (11) (125 mg,
0.336 mmol) to yield 12 (174 mg, 63%) as a yellow syrup. Rf 0.31
(7:3 hexaneÐEtOAc); [a]27D Ð27.9 (c = 1.2; CH2Cl2).
1H NMR (CDCl3): d = 7.77, 7.31 (2m, 15H, CH(Ph)), 5.91 (d, 1H,
H-1', J1Ð2 = 3.7 Hz), 4.76 (s, 1H, H-1), 4.66 (dd, 2H, CH2(Ph)), 4.60
(d, 1H, H-2'), 4.50 (d, 1H, H-2), 4.19 (dd, 1H, H-4, J4Ð5 = 8.9 Hz),
4.15Ð4.06 (m, 4H, H-3', H-4', H-5', H-5), 3.27 (s, 3H, CH3O), 2.49Ð
2.33 (m, 4H, H-6, H-6', H-6'', H-6'''), 1.46, 1.30, 1.25, 1.21 (4s, 12H,
C(CH3)2), 1.06 (s, 9H, C(CH3)3).
13C NMR (CDCl3): d = 137.4 (Cipso), 136.2, 136.0 (CH(Ph)), 134.2,
133.1 (Cipso), 129.6, 128.5, 128.0, 127.5, 127.3 (CH(Ph)), 111.9,
111.7 (C(CH3)2), 106.9 (C-1), 105.1 (C-1'), 84.9 (C-2), 82.5 (C-2'),
81.7 (C-4', C-3'), 80.7 (C-4), 79.8 (C-7), 79.4 (C-3), 77.9 (C-7'),
72.3 CH2(Ph), 68.7, 67.2 (C-5, C-5'), 54.1 (OCH3), 26.9 (C(CH3)3),
26.3, 25.9 (C(CH3)2), 25.3, 25.0 (C-6, C-6'), 24.6 (2 C(CH3)2), 19.3
(C(CH3)3).
IR (NaCl): n = 3280 cmÐ1 (C≡C-H), 3477 cmÐ1 (O-H)
C22H34O10
(458.50)
calcd
C
C
57.63
57.54
H
H
7.47
7.42
found
Methyl 5-O-tert-Butyldiphenylsilyl-6,7,8-trideoxy-2,3-O-iso-
propylidene-α-D-manno-oct-7-ynofuranoside (9)
To a solution of 6 (112.5 g, 0.46 mmol) in DMF (4 mL) was added
at r.t., imidazole (158 mg, 2.32 mmol) and TBDPSCl (302 mL,
1.16 mmol). The mixture was heated to 90¡C overnight. The mix-
ture was concentrated under reduced pressure and the residue was
dissolved in H2O (15 mL) and extracted with EtOAc (3 × 15 mL).
The combined organic layers were dried (Na2SO4), concentrated
under reduced pressure and the residue was chromatographed on
silica gel (98:2 hexaneÐEtOAc) to yield 9 (155 mg, 86 %) as a col-
orless syrup: Rf 0.68 (1:9 EtOAcÐhexane); [a]D25 +32.4 (c = 0.8,
CH2Cl2).
C44H56O10Si calcd
(773.00) found
C
C
68.37
68.29
H
H
7.30
7.47
1H NMR (CDCl3): d = 7.81, 7.37 (m, 10H, CH(Ph)), 4.82 (dd, 1H,
H-3, J2-3 = 5.8 Hz, J3Ð4 = 3.3 Hz), 4.79 (s, 1H, H-1), 4.54 (d, 1H, H-
2), 4.27 (dd, 1H, H-4, J4Ð5 = 8.9 Hz), 4.09 (m, 1H, H-5), 3.32 (s, 3H,
CH3O), 2.46 (dt, 1H, H-6, J5Ð6 = 5.9 Hz, J6Ð6' = 17.1 Hz, J6Ð8 = 2.5
Hz), 2.31 (dt, 1H, H-6', J5Ð6' = 6.1 Hz, J6'Ð8 = 2.5 Hz), 2.02 (t, 1H, H-
8), 1.26; 1.21 (2s, 6H, C(CH3)2), 1.10 (s, 9H, C(CH3)3).
6,7,8-Trideoxy-3-O-benzyl-1,2-O-isopropylidene-8-(methyl 6-
deoxy-2,3-O-isopropylidene-α-D-manno-furanosid-6-yl)-α-D-
gluco-oct-7-ynofuranose (13)
13C NMR (CDCl3): d = 136.2, 136.1 (CH(Ph)), 134.1, 133.2 (Cipso),
129.5, 127.5 (CH(Ph)), 111.9 (C(CH3)2), 106.8 (C-1), 85.0 (C-2), 80.8
(C-7), 80.2 (C-4), 79.4 (C-3), 70.6 (C-8), 68.1 (C-5), 54.1 (OCH3), 26.9
(C(CH3)3), 25.9, 24.6 (C(CH3)2), 24.5 (C-6), 19.4 (C(CH3)3).
Compound 13 was obtained quantitatively by treatment of 12 in
THF (7 mL) by TBAF (cat.). 13 as a colorless syrup. Rf 0.18 (7:3
hexane-EtOAc); [a]27D Ð1.5û (c = 0.4; CH2Cl2).
1H NMR (CDCl3): d = 7.28 (m, 5H, CH(Ph)), 5.87 (d, 1H, H-1',
J1Ð2 = 3.7 Hz), 4.84 (s, 1H, H-1), 4.80 (dd, 1H, H-3, J2Ð3 = 5.85 Hz,
J3Ð4 = 3.6 Hz), 4.69 (d, 1H, CH2(Ph)), 4.55 (2d, 2H, H-2', CH2(Ph)),
4.52 (d, 1H, H-2), 4.11Ð3.95 (m, 4H, H-3', H-4', H-5', H-5), 3.88
(dd, 1H, H-4, J4Ð5 = 7.95 Hz), 3.26 (s, 3H, CH3O), 2.64Ð2.43 (m,
4H, H-6, H-6', H-6'', H-6'''), 1.44, 1.42, 1.25(2) (3s, 12H, C(CH3)2).
IR (NaCl): n = 3303 cmÐ1 (C≡C-H)
C28H36O5Si calcd
(480.67) found
C
C
69.97
70.12
H
H
7.55
7.42
13C NMR (CDCl3): d = 137.2 (Cipso), 128.5, 128.0, 127.7 (CH(Ph)),
112.9, 111.7 (C(CH3)2), 106.9 (C-1), 105.0 (C-1'), 84.8 (C-2), 82.3
(C-2'), 81.7, 81.4 (C-4', C-3'), 80.5 (C-4), 79.8 (C-3), 78.6, 78.5 (C-
7, C-7'), 72.2 CH2(Ph), 68.2, 67.2 (C-5, C-5'), 54.4 (OCH3), 26.8,
26.3, 25.9 (C(CH3)2), 25.0, 24.8 (C-6, C-6'), 24.6 (2 C(CH3)2).
Methyl 6,7,8-Trideoxy-2,3-O-isopropylidene-8-(methyl 5-O-
tert-butyldiphenylsilyl-6-deoxy-2,3-O-isopropylidene-α-D-man-
no-furanosid-6-yl)-α-D-manno-oct-7-ynofuranoside (10)
To a solution of 9 (155.2 mg, 0.323 mmol) in THF (0.8 mL)/HMPA
(0.08mL) cooled to Ð5¡C was added under Ar a solution of BuLi
(129 mL of 2.5 M solution in THF, 0.323 mmol). The mixture was
stirred for 1 h at r.t. and then cooled to Ð5¡C. Compound 1 (0.105 g,
0.35 mmol) was added and the mixture was stirred at Ð5¡C over-
night and then mixture was treated as described above for 2, flash
chromatography on silica gel (9:1 hexaneÐEtOAc) to yield 10
(136 mg, 60.5%) as a colorless syrup. Desilylation with TBFA
(cat.) in THF (5mL) at r.t. yielded quantitatively 7 in 2 h. Rf 0.82
(6:4 hexaneÐEtOAc); [a]D25 +43.2 (c = 0.4, CH2Cl2).
1H NMR (CDCl3): d = 7.77, 7.28 (m, 10H, CH(Ph)), 4.83 (s, 1H, H-
1), 4.76 (dd, 1H, H-3, J2Ð3 = 5.9 Hz, J3Ð4 = 3.5 Hz), 4.72 (dd, 1H, H-
3', J2'Ð3' = 5.8 Hz, J3'Ð4' = 3.2 Hz), 4.69 (s, 1H, H-1'), 4.49 (d, 1H, H-
2), 4.44 (d, 1H, H-2'), 4.10 (dd, 1H, H-4', J4'Ð5' = 8.9 Hz), 3.99 (m,
2H, H-5, H-5'), 3.88 (dd, 1H, H-4, J4Ð5 = 7.7 Hz), 3.23, 3.22 (2s, 6H,
CH3O), 2.61Ð2.17 (m, 4H, H-6, H-6', H-6'', H-6'''), 1.40, 1.25, 1.16,
1.12 (4s, 12H, C(CH3)2), 0.98 (s, 9H, C(CH3)3).
C28H38O10
(534.60)
calcd
C
C
62.91
62.81
H
H
7.16
7.01
found
References
(1) Tomalia, D. A.; Falk, J. C. Heterocycl. Chem. 1972, 9, 891.
(2) Gao, Y. Ph.D. Thesis, Massachusetts Institute of Technology,
1988.
(3) Gao, Y.; Sharpless, K. B. J. Am. Chem. Soc. 1988, 110, 7538.
(4) Van der Klein, P. A. ; Boons, G. J. P. H.; Veeneman, G. H.;
Van der Marel, G. A.; Van Boom, J. H. Tetrahedron Lett.
1989, 30, 5477.
Van der Klein, P. A. ; Boons, G. J. P. H.; Veeneman, G. H.;
Van der Marel, G. A.; Van Boom, J. H. Synlett 1990, 31,
3637.
13C NMR (CDCl3): d = 136.1, 136.0 (CH(Ph)), 134.2, 133.1 (Cipso),
129.5, 127.2 (CH(Ph)), 112.5, 111.9 (C(CH3)2), 107.0 (C-1, C-1'),
84.9 (C-2, C-2'), 80.6 (C-4'), 80.4 (C-4), 79.9 (C-3), 79.5 (C-7), 79.4
(C-3'), 77.7 (C-7'), 68.6, 68.2 (C-5, C-5'), 54.4, 54.1 (OCH3), 26.8
(C(CH3)3), 25.9, 25.8 (C(CH3)2), 25.0, 24.9 (C-6, C-6'), 24.6 (2
C(CH3)2), 19.3 (C(CH3)3).
(5) Gomez, A. Z.; Valverde, S.; Fraser-Reid, B. J. Chem. Soc.,
Chem. Commun. 1991, 1207.
(6) Hoye, T. R.; Crawford, K. B. J. Org. Chem. 1994, 59, 520.
(7) Stiasny, H. C. Synthesis 1996, 2, 259.
Synthesis 1999, No. 2, 290–294 ISSN 0039-7881 © Thieme Stuttgart · New York

294
T. Gourlain et al.
PAPER
(8) Bates, R. W.; Fernandez-Moro, R.; Ley, S. V. Tetrahedron
Lett. 1991, 32, 2651.
(c) Daly, S. M.; Armstrong, R. W. Tetrahedron Lett. 1989, 30,
5713.
(9) Gourlain, T.; Wadouachi, A.; El Meslouti, A.; Uzan, R.;
Beaup•re, D. Carbohydr. Lett. 1996, 2, 143.
(10) Gourlain, T.; Wadouachi, A.; Beaup•re, D. J. Carbohydr.
Chem. 1997, 16(7), 1089.
(11) Sabesan, S.; Duus, J.; Neira, S.; Domaille, P.; Kelm, S.; Paul-
son, J. C.; Bock, K. J. Am. Chem. Soc. 1992, 114, 8363.
(12) (a) Lancelin, J. M.; Amvam Zollo, P. H.; SinaØ, P. Tetrahe-
dron Lett. 1983, 24, 4833.
(13) Sutherlin, D. P.; Armstrong, R. W. Tetrahedron Lett. 1993,
34, 4897.
(14) C-(ethynyl)-b-D-glucopyranoside 4 was initially prepared
from 2,3,4,6-tetra-O-benzylgluconolactone
Czernecki, S.; Ville, G. J. Org. Chem. 1989, 54, 610. Fol-
lowed by a reduction of the hemiacetal function with Et3SiH/
BF3 McDonald, F. E.; Zhu, H. Y. H.; Holmquist, C. R. J. Am.
Chem. Soc. 1995, 117, 6605.
(b) Rouzaud, D.; SinaØ, P. J. Chem. Soc., Chem. Commun.
1983, 1353.
(15) Calvo-Flores, F. G.; Garcia-Mendoza, P.; Hernandez-Mateo,
F.; Isac-Garcia, J.; Santoyo-Gonzalez, F. J. Org. Chem.
1997, 62, 3944.
Synthesis 1999, No. 2, 290–294 ISSN 0039-7881 © Thieme Stuttgart · New York