Studies directed towards the total synthesis of FK-506 preparation of a C(1) to C(15) segment

✍ Scribed by Robert E Ireland; Peter Wipf

• Publisher: Elsevier Science
• Year: 1989
• Tongue: French
• Weight: 254 KB
• Volume: 30
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)95278-x

✦ Synopsis

The protected C(1) to C(15) segment of FK-506 has been prepared from D-glucose, glycolic and L-pipecolic acid. The novel, highly active immunosuppressive agent FK-506 (1) has attracted considerable attention.1 The biological potency as well as some unique structural features render this 23-membered macrolide an ideal target for the development of new synthetic methodology on complex natural products. Moreover, a versatile synthesis for FK-506 will provide a ready access to analogues that will cast light upon the apparently similar mode of action of the neutral polyketide FK-506 and the undecapeptide cyclosporin.3 Such studies are likely to contribute to a better understanding of the regulation mechanisms in the immune system. With these goals in mind, we have embarked on a program directed towards the total synthesis of FK-506, the structurally related rapamycin3 and variants that will serve as probes in elucidation of the biological mode of action of these agents. Scheme I.