A Flexible Approach to Grandisine Alkaloids: Total Synthesis of Grandisines B, D, and F

✍ Scribed by Haruaki Kurasaki; Iwao Okamoto; Nobuyoshi Morita; Osamu Tamura

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 455 KB
• Volume: 15
• Category: Article
• ISSN: 0947-6539
• DOI: 10.1002/chem.200901843

✦ Synopsis

Abstract

This article describes in detail the first total synthesis of grandisine alkaloids, grandisines B, D, and F, which show affinity for the human δ‐opioid receptor. The key steps in this synthesis are construction of the isoquinuclidinone moiety of 2 by intramolecular imine formation and the tetracyclic ring system of 4 by stereoselective ring closure of the enolate of amine 8 generated by 1,4‐addition of ammonia to 9. Synthesis of key intermediate 9 featured a highly stereoselective Brønsted acid mediated Morita–Baylis–Hillman (MBH) reaction via the N‐acyl iminium ion.