Total synthesis of pamamycin 607: applications of remote asymmetric induction in organic synthesis

✍ Scribed by Olivier Germay; Naresh Kumar; Eric J Thomas

• Publisher: Elsevier Science
• Year: 2001
• Tongue: French
• Weight: 96 KB
• Volume: 42
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)00921-2

✦ Synopsis

A total synthesis of pamamycin 607 1 is described. The synthesis of the C(1)-C(18) fragment involved the tin(IV) chloride-promoted reaction between (3R)-3-(N-methyl)tosylaminohexanal 18 and the allylstannane 4 followed by cyclisation and reductive removal of the phenylselanyl group to give the tetrahydrofuran 20 which was taken through to the aldehyde 21. Aldol addition of the lithium enolate derived from 2,6-dimethylphenyl propanoate to this aldehyde followed by O-silylation gave the silyl ether 25 as the major product. This was converted into the aldehyde 31 which gave the bis-tetrahydrofuran 33 on reaction with the stannane 4, cyclisation and reduction. Exchange of the N-protecting group, hydrogenolysis and oxidation then gave the acid 34. This was esterified using the alcohol 42, which had been prepared from the aldehyde 35 and the stannane ent-4 using similar chemistry, to give the ester 43. Deprotection gave the seco-acid 44 and cyclisation, N-deprotection and N-methylation gave pamamycin 607 1.