General Approach for the Liquid-Phase Fragment Synthesis of Orthogonally Protected Naturally Occurring Polyamines and Applications Thereof.

Abstract

Orthogonally protected polyamines (PAs) have been synthesized using α,ω-diamines and ω-aminoalcohols as N-Cx-N and N-Cy synthons, respectively, and the Mitsunobu reaction as the key reaction for the assembly of the PA skeleta. The Trt, Dde, and Phth groups have been employed for protecting the primary amino functions and the Ns group for activating the primary amino functions toward alkylation and secondary amino function protection. The approach has been readily extended to accommodate the total synthesis of the spider toxins Agel 416 and HO-416b, incorporating the 3-4-3-3 and the 3-3-3-4 PA skeleton, respectively.