A fully stereocontrolled total synthesis of (+)-leucascandrolide A

✍ Scribed by Ian Paterson; Matthew Tudge

• Book ID: 104205465
• Publisher: Elsevier Science
• Year: 2003
• Tongue: French
• Weight: 448 KB
• Volume: 59
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(03)00814-7

✦ Synopsis

A highly stereocontrolled total synthesis of leucascandrolide A, a cytotoxic 18-membered macrolide from the calcareous sponge Leucascandra caveolata, starts out with a Jacobsen asymmetric hetero Diels -Alder reaction to configure the 2,6-cis-tetrahydropyran ring. All the remaining oxygenated stereocentres are introduced with high selectivity by relying on substrate-based control. An efficient endgame depends on two Mitsunobu reactions, the first to close the macrolactone with inversion at C17 and the second to attach the oxazole-containing side chain at C5, followed by Lindlar hydrogenation of the two alkynes to provide (þ)-leucascandrolide A.