Enantioselective Synthesis of the Cyclopiazonic Acid Family Using Sulfur Ylides

Abstract

A convergent, nine‐step (LLS), enantioselective synthesis of α‐cyclopiazonic acid and related natural products is reported. The route features a) an enantioselective aziridination of an imine with a chiral sulfur ylide; b) a bioinspired (3+2)‐cycloaddition of the aziridine onto an alkene; and c) installation of the acetyltetramic acid by an unprecedented tandem carbonylative lactamization/N−O cleavage of a bromoisoxazole.

Coupling of Sulfoxonium Ylides with Arynes: A Direct Synthesis of Pro-Chiral Aryl Ketosulfoxonium Ylides and Its Application in the Preparation of α-Aryl Ketones

“…Sulfonium and sulfoxonium ylides , have played significant roles in organic synthesis as important building blocks in total synthesis, − chemical materials, − and pharmaceuticals, − among others. , These ylides have also proven to be alternative metallocarbene surrogates to diazo compounds, having many reactions in common such as insertion, − cyclopropanation, epoxidation, aziridination, dimerizations, and Wolff , and Stevens rearrangements. , Furthermore, when compared with diazo compounds, these ylides are generally crystalline solids, more stable, have already been used in industrial scales, and are easier/safer to prepare (since they do not involve the use of potentially explosive compounds such as azides, diazomethane, and its derivatives) …”

α‐Cyclopiazonic Acid from Synthesis Perspective

“…The group of Aggarwal used a bioinspired retrosynthetic strategy using aziridine 38 as a gateway to the target molecule (Figure 2). [31a,b] This aziridine would be prepared from intermediates 39 and 40 using the group‘s sulfur ylide methodology [32]…”

A Ten‐Step Total Synthesis of Speradine C

“…To date, five total syntheses of the related but far less functionalized α‐CPA have been reported . However, of the highly oxygenated CPA‐derived alkaloids, only aspergilline A has succumbed to total synthesis .…”