J. Am. Chem. Soc. 1997, 119, 2335-2336
A Fundamentally New, Simple, Stereospecific Synthesis of Oligosaccharides Containing the β-Mannopyranosyl and β-Rhamnopyranosyl Linkage Gyo¨rgy Hodosi* and Pavol Kova´cˇ NIDDK, Section on Carbohydrates, LMC National Institutes of Health Bethesda, Maryland 20892-0815 ReceiVed NoVember 20, 1996 The important role of oligosaccharides in biological processes1 has been recognized for a long time. Consequently, synthetic oligosaccharides have become indispensable probes for the life sciences.2 Methods for the chemical synthesis of oligosaccharides are based on a two-step process: The first comprises activation of the anomeric center to generate a glycosyl donor, and the second is its transfer to a glycosyl acceptor. The stereochemical outcome of the reaction depends on complex stereoelectronic effects as well as the presence or absence of groups at O-2 in the glycosyl donor capable of neighboring group participation.3 Except for rare cases, when the coupling of a glycosyl donor and a glycosyl acceptor occurs as an almost entirely SN2 process,4 the reaction of the glycosyl donor involves the formation of the oxocarbenium ion (1). Thus, the nonstereospecificity of glycosylation is virtually inherent in the method.
Syntheses of 1,2-trans-linked oligosaccharides are relatively easy, but not the highly stereoselective syntheses of their 1,2cis-linked counterparts. Most difficult are syntheses of β-mannosides and β-rhamnosides.5 Both the anomeric effect, which favors the formation of the R-mannopyranosyl linkage, and the formation of 1 during the transition state of the reaction are largely responsible for this unfavorable situation. Efforts aimed at overcoming these difficulties continue, and some new approaches have recently been introduced.6 Nevertheless, there is still a need for more efficient methods of glycosylation not involving the formation of the oxocarbenium ion. We have now discovered that 1,2-O-cis-stannylene acetals of sugars are powerful nucleophiles capable of displacing, Via the SN2 process, good leaving groups in carbohydrates. This (1) Varki, A. Glycobiology 1993, 3, 97-130. (2) Synthetic Oligosaccharides. Indispensable Probes in the Life Sciences; Kova´cˇ, P., Ed.; American Chemical Society: Washington, DC, 1994; Vol. 560. (3) (a) Schmidt, R. R. Angew. Chem., Int. Ed. Engl. 1986, 25, 212235. (b) Paulsen, H. Angew. Chem., Int. Ed. Engl., 1982, 21, 155-173. (c) Schmidt, R. R. In ComprehensiVe Organic Synthesis; Trost, B. M., Ed.; Pergamon Press: New York, 1991; Vol. 6; pp 33-64. (d) Khan, S. H.; Hindsgaul, O. In Molecular Glycobiology; Fukuda, M., Hindsgaul, O., Eds.; IRL Press: Oxford, 1994; pp 206-229. (4) (a) Lemieux, R. U.; Hendriks, K. B.; Stick, R. V.; James, K. J. Am. Chem. Soc. 1975, 97, 4056-4062. (b) Paulsen, H.; Lockhof, O. Ber. Dtsch. Chem. Ges. 1981, 114, 3102-3114. (c) Paulsen, H.; Lebuhn, R.; Lockhoff, O. Carbohydr. Res. 1982, 103, C7-C11. (d) Garegg, P. J.; Ossowski, P. Acta Chem. Scand. 1983, B37, 249-254. (e) Schmidt, R. R.; Reichrath, M.; Moering, U. Chem. Ber. 1982, 115, 39-49. (5) Baresi, F.; Hindsgaul, O. In Modern Methods in Carbohydrate Synthesis; O’Neill, S. H. K. a. R. O., Ed.; Harwood Academic Publishers GmbH: Amsterdam, 1996; Vol. 1, pp 251-276. (6) (a) Ito, Y.; Ogawa, T. Angew. Chem., Int. Ed. Engl. 1994, 33, 1087. (b) Stork, G.; Kim, G. J. Am. Chem. Soc. 1992, 114, 1087-1088. (c) Baresi, F.; Hindsgaul, O. J. Am. Chem. Soc. 1991, 113, 9376. (d) Stork, G.; La Clair, J. J. Am. Chem. Soc. 1996, 118, 247-248.
S0002-7863(96)04021-8
2335
Table 1. Reaction Conditions Applied and Yields Obtained Elb yield Nua equiv equiv prod (%)
solvent
7/4.5 7/4.5 11/4 11/3 11/6 11/6 11/6 12/5 12/6
DMF -5 80 min DMF 25 2.5 h DMF 0, 25 4 h, 10 h CH3CN 25 20 h DMF 25 5d DMAA 25 3d DMSO 25 2d CH3CN 25 14 h DMF 25 18 h
a
5/1 9/1 5/1 5/1 9/1 9/1 9/1 5/1 9/1
8 10 13 13 18 18 18 14 19
88 78 40 57 40 52 59 75 67
temp (°C)
reaction time
salt/ equiv CsF/6 CsF/6 Bu4NF/1
Bu4NF/1 CsF/6
Nucleophile. b Electrophile.
Table 2. Characteristic Data for Newly Synthesized Substancesa compd 5 6c,d 8e 10 13 14 16 18e 19
[R]Db deg
δH-1I/ J1,2 Hz
150-151 +127 +142 +30 +16 +56 106-107 +104 +83
5.26/3.7 5.16/3.2 5.24/3.7 5.15/3.4 5.22/3.3 5.22/3.7 5.17/3.5 5.13/3.6 5.12/3.7
mp (°C)
δH-1II /J1,2 Hz
δC-1I/ JC,H (Hz)
δC-1II/ JC,H (Hz)
4.52/
