Stereoselective synthesis of α-C-glycopyranosyl isoprenoid compounds

Article abstract of DOI:10.1055/s-1998-3125

Addition of the allylsilane Me₃SiCH₂C:CH₂CH₂CO₂Me (3) to D-gluco and D-galactopyranosyl derivatives gives in good yields 3-(α-C-glycopyranosylmethyl)-but-3-enoates which can undergo oxidation to β-ketoesters, electrophile-promoted cyclizations or double bond migration.

Full text of DOI:10.1055/s-1998-3125

January 1998
SYNLETT
81
Stereoselective Synthesis of α-C-Glycopyranosyl Isoprenoid Compounds
Anne Jégou, Carole Pacheco, Alain Veyrières*
Laboratoire de Synthèses et Activations de Biomolécules, CNRS ESA 6052, Ecole Nationale Supérieure de Chimie de Rennes, Campus de Beaulieu,
35700 Rennes, France
Fax + 33(2)99871348
Received 20 October 1997
Abstract: Addition of the allylsilane Me SiCH C:CH CH CO Me (3)
3
2
2
2
2
to D-gluco and D-galactopyranosyl derivatives gives in good yields 3-
(α-C-glycopyranosylmethyl)-but-3-enoates which can undergo oxida-
tion to β-ketoesters, electrophile-promoted cyclizations or double bond
migration.
Isopentenyl pyrophosphate (1) and its isomerization product, dimethyl-
1
allyl pyrophosphate (2), are well-known five-carbon building blocks
involved in the terpenoid biosynthesis. These activated forms of iso-
2,3
prene can be chemically mimicked by the allylsilane 3 which is easily
2,4
obtained by reaction of diketene with the Grignard reagent of chloro-
methyltrimethylsilane, followed by diazomethane esterification.
2
5
Addition of 3 to carbonyl compounds or iminium ions occurs in high
yields, the presence of a carboxylate function then allowing an easy
double bond migration to yield a conjugated product.
Herein we report the stereoselective addition of 3 to oxocarbenium
6
species generated from pyrano sugars (Table 1) and various trans-
7
formations of the resulting C-glycosides.
The stereoselective synthesis of α-C-allyl glycopyranosides from per-
8
acyl hexopyranoses has been described. However, β-D-glucopyranose
.
pentaacetate (4) reacted sluggishly with 3 and BF OEt in acetonitrile
3
2
to give a 6:1 mixture of α- and β-C-glycosides 5 in only 24% yield.
9,10
More reactive perbenzylated fluorides
6 and 9 gave C-glycosides 7
1
and 10, respectively in much higher yields and stereoselectivities.
H
NMR analysis of 7α and 10α in CDCl at room temperature showed
3
complex mixtures of conformers at the pyranose ring. The expected
multiplicity of anomeric H-5 (ddd, J
11, J
3.3 and J 5.6 Hz)
5,6
4a,5
4b,5
11
was however observed in DMSO-d at 80°C. Pertrimethylsilylated
6
12,13
sugars have been rarely used
for C- and O-glycoside synthesis.
Silylation of methyl α-D-gluco and galactopyranosides gave 12 and 14
which reacted with silane 3 and trimethylsilyl trifluoromethanesulfonate
(TMSOTf) to give after desilylation unprotected C-glycosides 13 and
14
15 respectively in good yields and selectivities.
Brief treatment of methylene compounds 7 and 10 by ozone at -78°C,
15
followed by reaction with triphenylphosphine gave β-ketoesters 8 and
11 respectively. A minor product resulting from regioselective oxidation
of the 7-O-benzyl group into a benzoate was isolated in 6% yield after
ozonolysis of the D-gluco compound 7. γ-Furanosyl and pyranosyl-β-
16
ketoesters have been previously prepared by a non stereoselective
Wittig reaction of phosphorane Ph P=CHC:OCH CO R with a sugar
3
2
2
hemiacetal.
Attempted debenzylation of 7 by anhydrous ferric chloride in dichloro-
17
methane , followed by acetylation, led to the bicyclic product 16 in
62% yield (Scheme 1). Activation of the double bond of 10 with iodine
also led to the addition of O-6 with loss of the benzyl group. Treatment

82
LETTERS
SYNLETT
of iodoether 17 (3:2 mixture of C-2 epimers) by zinc and acetic acid
gave the C-glycoside 18 selectively debenzylated at O-6 (Scheme 1).
(8) Giannis, A.; Sandhoff, K. Tetrahedron Lett. 1985, 26, 1479;
Horton, D.; Miyake, T. Carbohydr. Res. 1988, 184, 221; Garcia
Martin, M.de G.; Horton, D. Carbohydr. Res. 1989, 191, 223.
18
A stereoselective access to α-C-glycoside of D-galactosamine from 18
19
should then be possible.
(9) Glucopyranosyl (6, α: β 4:1) and galactopyranosyl (9, α: β 9:1)
fluorides were prepared from the corresponding β-thiophenyl
pyranosides: Nicolaou, K.C.; Caulfield, T.J.; Kataoka, H.
Carbohydr. Res. 1990, 202, 177.
Conjugation of the double bond in 7 was accomplished by treatment
20
with piperidine in refluxing tetrahydrofuran (Scheme 2). A 4:1
mixture of E and Z isomers 19 was obtained in 83% yield.
(10) Nicolaou, K.C.; Dolle, R.E.; Chucholowski, A.; Randall, J.L. J.
Chem. Soc., Chem. Commun. 1984, 1153.
1
(11) 7α: mp 42-45°C; [α] +20 (c 1, CHCl ); H NMR (400 MHz,
D
3
DMSO-d , 80°C) δ 7.34-7.21 (m, 20H, 4 Ph), 5.03 and 4.94 (2 bd
6
s, 2H, CH =), 4.83 and 4.73 (2 d, 2H, J 11.5 Hz, CH Ph), 4.73 and
2
2
4.55 (2 d, 2H, J 11.3 Hz, CH Ph), 4.63 (m, 2H, CH Ph), 4.51 and
2
2
4.46 (2 d, 2H, J 12.1 Hz, CH Ph), 4.23 (ddd, 1H, J
11, J
4b,5
2
4a,5
3.3, J 5.6 Hz, H-5), 3.78 (dd, 1H, J 8.8, J 8.2 Hz, H-7),
5,6
6,7
7,8
3.70 (m, 1H, H-9), 3.65 (dd, 1H, H-6), 3.62-3.58 (m, 2H, H-
10a,10b), 3.60 (s, 3H, CO Me), 3.46 (dd, 1H, J 9.4 Hz, H-8),
2
8,9
3.14 (bd s, 2H, H-2a,2b), 2.60 (dd, 1H, J
(dd, 1H, H-4b); C NMR (100.6 MHz, CDCl ) δ 171.90 (C-1),
15.4 Hz, H-4a), 2.41
4a,4b
13
3
139.37, 138.80, 138.24, 138.23 and 138.08 (C-3, 4 C quat. arom.),
128.51-127.69 (20 C arom.), 116.64 (CH =), 82.42, 79.96, 78.03,
2
72.68 and 71.26 (C-5,6,7,8,9), 75.60, 75.22, 73.54 and 73.05 (4
CH Ph), 68.85 (C-10), 51.92 (CO CH ), 41.31 (C-2), 30.75 (C-4).
2
2
3
Calcd for C
H O : C, 75.45; H, 6.96. Found: C, 75.44; H, 7.13.
40 44 7
21
1
Assignment of the stereochemistry was made on the basis of H and
(12) Bennek, J.A.; Gray, G.R. J. Org. Chem. 1987, 52, 892.
(13) Uchiyama, T.; Hindsgaul, O. Synlett 1996, 499.
13
22
C chemical shifts of Me and CH -4 groups. In the E isomer these
2
signals occur respectively at δ 2.16, δ 18.56 and δ
2.48, δ 36.18, whereas in the Z isomer the following values are found:
2.58, δ
H-4b
H
C
H-4a
1
(14) 15α: mp 103-5°C; [α] +73 (c 1, MeOH); H NMR (400 MHz,
D
C
CD OD) δ 5.05 and 4.96 (2 bd s, 2H, CH =), 4.14 (ddd, 1H, J
δ
1.92, δ 25.55 and δ
3.34, δ
2.95, δ 28.69.
H-4b C
3
2
4a,5
H
C
H-4a
11.2, J
3.1, J 5.6 Hz, H-5), 3.94 (m, 1H, H-8), 3.91 (dd, 1H,
5,6
4b,5
Finally, C-glycoside 7 was treated with a catalytic amount of osmium
tetroxide and N-methylmorpholine oxide (NMO) to give the
lactonized diol 20 as a 7:3 mixture of epimers at C-3. Treatment of 20
J
9.2 Hz, H-6), 3.76-3.64 (m, 4H, H-7,9,10a,10b), 3.67 (s, 3H,
23
6,7
CO Me), 3.18 (m, 2H, H-2a,2b), 2.55 (dd, 1H, J
15.3 Hz, H-
2
4a,4b
13
4a), 2.43 (dd, 1H, H-4b); C NMR (100.6 MHz, CD OD) δ
174.00 (C-1), 141.60 (C-3), 116.75 (CH =), 74.79, 73.88, 71.82,
70.04 and 69.99 (C-5,6,7,8,9), 61.96 (C- 10), 52.36 (CO CH ),
3
with methanesulfonyl chloride and triethylamine gave the butenolide
24
2
21 in a 63% overall yield from 7.
2
3
42.08 (C-2), 32.36 (C-4).
1
(15) 8α: [α] +33 (c 1, CHCl ); H NMR (400 MHz, CDCl ) δ 7.33-
D
3
3
References and Notes
7.24 (m, 20H, 4 Ph), 4.89 and 4.79 (2 d, 2H, J 11.2 Hz, CH Ph),
2
(1) Hanson, J.R. In Comprehensive Organic Synthesis, Vol.5; Barton,
D.; Ollis, W.D.; Haslam, E., Eds; Pergamon Press: Oxford, 1979;
p 989.
4.79 and 4.56 (2 d, 2H, J 11.7 Hz, CH Ph), 4.69 (m, 1H, H-5),
2
4.61 and 4.47 (2 d, 2H, J 11.2 Hz, CH Ph), 4.59 and 4.46 (2 d, 2H,
2
J 12.2 Hz, CH Ph), 3.78-3.55 (m, 6H, H- 6,7,8,9,10a,10b), 3.68
2
(s, 3H, CO Me), 3.48 and 3.41 (2 d, 2H, J
15.8 Hz, H-2a,2b),
(2) Itoh, K.; Fukui, M.; Kurachi, Y. J. Chem. Soc., Chem. Commun.
1977, 500.
2
2a,2b
3.01 (dd, 1H, J
15.6, J
5.8 Hz, H-4a), 2.82 (dd, 1H, J
4a,4b
13
4a,5 4b,5
8.1 Hz, H-4b); C NMR (100.6 MHz, CDCl ) δ 200.15 (C-3),
3
(3) Itoh, K.; Yogo, T.; Ishii, Y. Chem. Lett. 1977, 103; Nishiyama, H.;
Itagaki, K.; Takahashi, K.; Itoh, K. Tetrahedron Lett. 1981, 22,
1691.
167.42 (C-1), 138.47, 138.01, 137.87 and 137.67 (4 C quat.
arom.), 128.52-127.68 (20 C arom.), 81.87, 79.06, 77.57, 72.55
and 70.83 (C- 5,6,7,8,9), 75.38, 75.00, 73.51 and 73.38 (4
(4) Armstrong, R.J.; Weiler, L. Can. J. Chem. 1983, 61, 2530.
CH Ph), 68.73 (C-10), 52.30 (CO CH ), 49.61 (C-2), 40.24 (C-4).
2
2
3
(5) Aratani, M.; Sawada, K.; Hashimoto, M. Tetrahedron Lett. 1982,
23, 3921; Oumoch, S.; Rousseau, G. Bioorg. Med. Chem. Lett.
1994, 4, 2841.
Calcd for C
H O : C, 73.33; H, 6.63. Found: C, 73.25; H, 6.57.
39 42 8
(16) Lopez Herrera, F.J.; Uraga Baelo, C. Carbohydr. Res. 1985, 139,
95; Lopez Herrera, F.J.; Uraga Baelo, C. Carbohydr. Res. 1985,
143, 161; Sun, K.M.; Dawe, R.D.; Fraser-Reid, B. Carbohydr.
Res. 1987, 171, 35.
(6) Ethoxycarbenium ion related to squaric acid has been allylated by
3 in 82% yield: Yamamoto, Y.; Ohno, M.; Egushi, S. Chem. Lett.
1995, 525.
(17) Rodebaugh, R.; Debenham, J.S.; Fraser-Reid, B. Tetrahedron
(7) Pseudomonic acids, a group of compounds with antimicrobial
activity produced by a strain of Pseudomonas fluorescens, bear a
five-carbon unit, 3-methyl-but-2-enoate, linked at C-2 of a tetra-
hydropyran unit. Biosynthetic studies showed that a 3-methyl-
but-3-enoyl CoA is attached to a polyketide chain which sub-
sequently undergoes a cyclization to the tetrahydropyranyl ring:
Feline, T.C.; Jones, R.B.; Mellows, G.; Phillips, L. J. Chem. Soc.,
Perkin Trans. 1 1977, 309.
Lett. 1996, 37, 5477.
1
(18) 18: H NMR (400 MHz, CDCl ) δ 7.37-7.22 (m, 15H, 3 Ph), 5.02
3
and 4.97 (2 bd s, 2H, CH =), 4.73, 4.72, 4.56 and 4.54 (4 d, 4H, J
2
11.7 Hz, 2 CH Ph), 4.52 and 4.48 (2 d, 2H, J 11.7 Hz, CH Ph),
2
2
4.23 (ddd, 1H, J
9.7, J
~ J ~ 4.6 Hz, H-5), 4.13-4.01 (m,
4a,5
4b,5 5,6
3H, H-8,10a,10b), 3.82 (dd, 1H, J ~ 10 Hz, H-6), 3.71-3.60 (m,
2H, H-7,9), 3.64 (s, 3H, CO Me), 3.16 and 3.11 (2 d, 2H, J 15.8
6,7
2

January 1998
SYNLETT
83
Hz, H-2a,2b), 2.47 (dd, 1H, J
H-4b); H NMR (400 MHz, CDCl + CCl CONCO) δ 8.67 (bd s,
15.3 Hz, H-4a), 2.39 (dd, 1H,
MHz, CDCl ) δ 7.40-7.13 (m, 20H, 4 Ph), 5.76 (bd s, 1H, H-2),
3
4.95 and 4.47 (2 d, 2H, J 10.7 Hz, CH Ph), 4.81 (m, 2H, CH Ph),
2 2
4a,4b
1
3
3
1H, NH), 7.39-7.26 (m, 15H, 3 Ph), 5.17 (m, 1H, H-6), 5.00 and
4.98 (2 bd s, 2H, CH =), 4.76 and 4.64 (2 d, 2H, J 12 Hz, CH Ph),
4.79 and 4.69 (2 d, 2H, J 11.7 Hz, CH Ph), 4.57 and 4.43 (2 d, 2H,
2
J 12.2 Hz, CH Ph), 4.40 (ddd, 1H, J
11.7, J
3.1, J 5.6
2
2
2
4a,5
4b,5 5,6
4.66 and 4.54 (2 d, 2H, J 11.7 Hz, CH Ph), 4.55 (s, 2H, CH Ph),
Hz, H-5), 3.86-3.75 (m, 3H, H-6,7,9), 3.69-3.55 (m, 3H, H-
2
2
4.31 (m, 1H, H-5), 4.20 (m, 1H, H-9), 4.01 (dd, 1H, J
~ 8,
8,10a,10b), 3.64 (s, 3H, CO Me), 3.34 (dd, 1H, J
4a), 2.95 (dd, 1H, H-4b), 1.92 (s, 3H, Me); C NMR (100.6 MHz,
14.2 Hz, H-
9,10a
2
4a,4b
13
J
11 Hz, H-10a), 3.94 (dd, 1H, J 2.8, J 4.7 Hz, H-8),
10a,10b
7,8
8,9
3.90 (dd, 1H, J 5.7 Hz, H-7), 3.73 (dd, 1H, J
3.9 Hz, H-
CDCl ) δ 166.55 (C-1), 157.86 (C-3), 138.82, 138.42, 138.37 and
6,7
9,10b
3
10b), 3.64 (s, 3H, CO Me), 3.14 and 3.08 (2 d, 2H, J 15.6 Hz, H-
138.08 (4 C quat. arom.), 128.37- 127.55 (20 C arom.), 117.59 (C-
2), 82.28, 80.29, 78.07, 73.70 and 71.80 (C-5,6,7,8,9), 75.53,
2
2a,2b), 2.46 (dd, 1H, J
15.2, J
8.8 Hz, H-4a), 2.34 (dd, 1H,
4a,4b
4a,5
J
4.5 Hz, H-4b).
74.92, 73.40 and 73.23 (4 CH Ph), 69.00 (C-10), 50.88
2
4b,5
(CO CH ), 28.69 (C-4), 25.55 (Me).
(19) Cipolla, L.; Lay, L.; Nicotra, F. Carbohydr. Lett. 1996, 2, 131.
(20) Miginiac, P.; Zamlouty, G. J. Organomet. Chem. 1975, 96, 163.
2
3
(22) Crimmin, M.J.; O’Hanlon, P.J.; Rogers, N.H. J. Chem. Soc.,
Perkin Trans. 1 1985, 541.
(21) (E)-19: mp 76-8°C; [α] +49 (c 0.98, CHCl ); R 0.16 (19:1
D
3
f
1
(23) Crich, D.; Lim, L.B.L. J. Chem. Soc., Perkin Trans. 1 1991, 2209.
toluene-EtOAc); H NMR (400 MHz, CDCl ) δ 7.34-7.11 (m,
3
1
20H, 4 Ph), 5.72 (bd s, 1H, H-2), 4.93, 4.81 and 4.46 (3d, 4H, J
(24) 21: mp 113-5°C; [α] +44 (c 0.99, CHCl ); H NMR (400 MHz,
D
3
11.2 Hz, 2 CH Ph), 4.73 and 4.60 (2 d, 2H, J 11.7 Hz, CH Ph),
C D ) δ 7.10-6.75 (m, 20H, 4 Ph), 5.41 (bd s, 1H, H- 2), 4.63 and
6 6
2
2
4.62 and 4.43 (2 d, 2H, J 12.2 Hz, CH Ph), 4.24 (ddd, 1H, J
4.26 (2 d, 2H, J 11.2 Hz, CH Ph), 4.57 (m, 2H, CH Ph), 4.16 and
2 2
2
4a,5
11.2, J
2.5, J
5.6 Hz, H-5), 3.78-3.57 (m, 6H, H-
3.91 (2 d, 2H, J 11.6 Hz, CH Ph), 4.06 and 3.98 (2 d, 2H, CH Ph),
4b,5
5,6
2
2
6,7,8,9,10a,10b), 3.65 (s, 3H, CO Me), 2.58 (dd, 1H, J
14.8
C
3.93 and 3.81 (2 dd, 2H, J
11a,11b), 3.48 (dt, J ~ 7.2, J ~ 5.9 Hz, H-5), 3.38-3.13 (m,
4,5 5,6
~ J
~ 1, J 17.5 Hz, H-
11a,11b
2
4a,4b
2,11a
2,11b
13
Hz, H-4a), 2.48 (dd, 1H, H-4b), 2.16 (d, 3H, J
1 Hz, Me);
2,Me
13
NMR (100.6 MHz, CDCl ) δ 166.99 (C- 1), 156.98 (C-3), 138.76,
6H, H-6,7,8,9,10a,10b), 1.91 (d, 2H, H-4a,4b); C NMR (100.6
MHz, C D ) δ 171.81 (C-1), 164.88 (C-3), 137.93, 137.66, 137.30
3
138.23, 138.19 and 138.11 (4 C quat. arom.), 128.68-127.72 (20 C
arom.), 117.60 (C-2), 82.46, 80.03, 78.04, 72.48 and 71.64 (C-
6
6
and 137.15 (4 C quat. arom.), 126.96-126.44 (20 C arom.), 116.18
(C-2), 80.76, 78.70, 77.11, 71.26 and 70.99 (C-5,6,7,8,9), 73.93,
5,6,7,8,9), 75.67, 75.26, 73.65 and 73.63 (4 CH Ph), 68.80 (C-
2
10), 50.97 (CO CH ), 36.18 (C-4), 18.56 (Me). (Z)-19: [α] +46
73.72, 72.32, 72.29 and 71.43 (4 CH Ph, C-11), 23.39 (C-4).
2
2
3
D
1
(c 0.99, CHCl ); R 0.25 (19:1 toluene-EtOAc); H NMR (400
3
f