Synthesis of ring-contracted, 25-nor-6,5-spiroketal-modified avermectin derivatives

✍ Scribed by Peter T. Meinke; Stephen P. O'Connor; Helmut Mrozik; Michael H. Fisher

• Book ID: 104224963
• Publisher: Elsevier Science
• Year: 1992
• Tongue: French
• Weight: 266 KB
• Volume: 33
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)91896-3

✦ Synopsis

A bstrtlcf: A versatile, high yielding strategy for the synthesis of ring-contracted, 25-nor-6,5-spirokelfll-l~lo~i~~~(~ avermectin analogs (7A -7N) bearing diverse suhstituents at C24 is described. In addition, an efficient Ph(0Ac)~mediuted oxidative cleavage to produce the key intermediate, aldehyde 3, is presented.

Avermectin

B1a (la, AVM), the primary fermentation product of Streptomyces avermitilis, xxi it< derivatives are structurally complex and useful natural products with pronounced biological activities. The 22,23dihydro derivative, ivermectin (lb), for instance, has found widespread use as a potent, broad spectrum anthelrnintic agent.' The novel molecular architecture and impressive biological activities of these macrolides his