A chemoenzymatic synthesis of the C10-C19 moiety of fk506

✍ Scribed by Rui-Lin Gu; Charles J. Sih

• Publisher: Elsevier Science
• Year: 1990
• Tongue: French
• Weight: 211 KB
• Volume: 31
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)89044-9

✦ Synopsis

Summan: Thu strategy usnd in the synthesis of thu C&s sngmont of A<506 is duscribed. The potent immunosuppnrtiw proportia of FKS6, 1, a macrolido produd by Shpfomyces fsddaonsis', was fin) doscribod by O&iii ot al.* in 1987. FK5M is structurally unrelated to cyclosporin A but shores many of its proportia in thn impairment of Tall rqonsw.s While the toxicity profile' of FK506 is not fully understood, a vary recent study rovoalod that R<506 was remarkably offoctivo as an immunosuppressont in human organ transplantation without serious side effoct~~ The vast thorapwtic potential and structural complexity of FKS6 havo mado it an attmctivo synthetic target and sovaral imaginative syntheses of various segments6 as wall as one total synthesis' of FK5M have bonn nporhd. tlowovor, this problem merits continuing attention bocauso oath synthetic variant offers un'qw opportunitia for structural altorations to probe the subtle relationship botwoen chomikxd structun and biiog'cal a&ii. Ho&n, wo disclosa progress of our chemoenzymatic approach looding to the proporation of 4'. which ropraonts the C,,-C,, segment of 1.