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- Title
Synthesis of the 6- C-Methyl and 6- C-(Hydroxymethyl) Analogues of N-Acetylneuraminic Acid and of N-Acetyl-2,3-didehydro-2-deoxyneuraminic Acid.
- Authors
Vasella, Andrea; Wyler, René
- Abstract
The synthesis of 6- C-methyl-Neu2en5Ac ( 4), 6-C-(hydroxymethyl)-Neu2en5Ac ( 5), and 6- C-methyl-Neu5Ac ( 6) is described. The 4-methylumbellyferyl glycosides 8 and 9 were also prepared but proved unstable. Protection of the previously reported nitro ether 10 (→ 11) followed by a Kornblum reaction gave the branched-chain derivative 13 which was transformed into aldehyde 14 and hence via 16 into the-protected 6- C-hydroxymethylated 20 and into the 6- C-methyl-substituted 18 ( Scheme 1). Debenzylidenation of 20 and 18 afforded the diols 21 and 19, respectively. Selective oxydation of 19 followed by esterification (→ 22), acetylation (→ 23), and elimination led to the protected 6- C-methyl-Neu2en5Ac derivative 24 ( Scheme 2). Bromomethoxylation yielded mainly 25 and some 26, which were reductively debrominated to 27 and 28, respectively. Attempted deprotection of 27 did not lead to the corresponding acid, but to the 2,7- and 2,8-anhydro compounds 29 and 30 which were characterised as their peracetylated esters 31 and 32 ( Scheme 3). The structure of 32 was established by X-ray analysis. Oxydation of 19 and 21, followed by deprotection, esterification, and acetylation gave 37 and 38, respectively ( Scheme 4). The branched-chain Neu2en5Ac derivatives 4 and 5 were obtained by β-elimination (→ 39 and 40) and deprotection. Omission of the esterification after oxydation of 33 and 34 gave the lactones 35 and 36 which were transformed into 37 and 38, respectively. Bromoacetoxylation of 39 gave 41-43 which were reductively debrominated to 44 (from 41 and 42) and 45 ( Scheme 5). Bromoacetoxylation of 40 yielded 46 which was debrominated to 47. Glycosidation of the glycosyl chlorides obtained from 44 and 47 led to the α -D-glycosides 48 and 49 and to the elimination products 39 and 40, respectively ( Scheme 6). Transesterification of 48, followed by saponification gave the unstable glycoside 8 and hence 6- C-methyl-Neu5Ac ( 6). The unstable glycoside 9 was obtained by similar treatment of 49 but yielded 50 under acidic conditions. The branched-chain 4 and 5 were weak inhibitors of Vibrio cholera sialidase, and 8 and 9 were very poor substrates.
- Publication
Helvetica Chimica Acta, 1990, Vol 73, Issue 6, p1742
- ISSN
0018-019X
- Publication type
Article
- DOI
10.1002/hlca.19900730620