The Chemistry of Vicinal Tricarbonyls: Total Syntheses of Elastase Inhibitors YM-47141 and YM-47142

✍ Scribed by Harry H. Wasserman; Jyun-Hung Chen; Mingde Xia

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: German
• Weight: 210 KB
• Volume: 83
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/1522-2675(20000906)83:9<2607::aid-hlca2607>3.0.co;2-b

✦ Synopsis

Dedicated to Professor Albert Eschenmoser on the occasion of his 75th birthday

We have completed the total syntheses of elastase inhibitors YM-47141 and YM-47142, the first natural products containing a vicinal tricarbonyl group. The work establishes the configuration at C(4) of the macrocyclic depsipeptide and demonstrates the generality of the phosphoranylidene-ylide activation and protection methodology employed earlier in syntheses of a-keto amides. Key steps involve the coupling of a carboxylic acid with a phosphorane to form a stable ylide intermediate, which contains the highly electrophilic carbonyl group in protected form. The tricarbonyl unit was unmasked at the final stage of the synthesis by oxidative cleavage of the CP bond.