Toward the Creation of Induced Pluripotent Small (iPS) Molecules: Establishment of a Modular Synthetic Strategy to the Heronamide C-type Polyene Macrolactams and Their Conformational and Reactivity Analysis

Abstract

A highly modular synthetic strategy to the heronamide C-type polyene macrolactams was established by synthesizing 8-deoxyheronamide C (2). The developed strategy enabled not only the total synthesis of 8-deoxyheronamide C (2) but also the unified synthesis of four heronamide-like molecules named "heronamidoids" (5-8). Conformational and reactivity analysis of the heronamidoids clarified that (1) the C19 stereochemistry mainly affected the conformation of the amide linkage, resulting in the change of alignment of two polyene units and reactivity towards photochemical [6p+6p] cycloaddition, and (2) the C8,C9-diol moiety is important for the conversion to the heronamide A-type skeleton from the heronamide C skeleton.

Substituent effects on the selectivity of ambimodal [6+4]/[4+2] cycloaddition

“…Heronamide A is a typical compound of ambimodal [6+4]/[4+2] cycloaddition and has been frequently studied in the past decades. [39][40][41][42][43][44][45][46][47] To reduce the time required for individual computation we choose cycloheptadecapentaene (reactant of R0), which was reported by Houk's group in 2015. 15 Compared to Heronamide A, cycloheptadecapentaene omits functional groups that have little effect on the reaction, replaces some atoms and retains the basic framework of ambimodal cycloaddition, making the system simpler.…”