Bioinspired total synthesis of boneratamides A-C

Org Biomol Chem. 2022 Nov 2;20(42):8236-8242. doi: 10.1039/d2ob00486k.

Abstract

We disclose the first synthesis of the marine natural product, (+)-boneratamide A, whose structure is composed of a terpene unit linked via an amide bond to a pyroglutamic acid moiety. The key step in this route is a bioinspired Ugi reaction of (+)-axisonitrile-3 with acetone as the carbonyl component and L-glutamic acid. This reaction brings about a remarkably efficient, one-pot assembly of reaction components concomitant with γ-lactam ring formation to produce (+)-boneratamide A in 70% yield. (+)-Boneratamide B and (-)-boneratamide C methyl esters were also synthesized using a similar bioinspired strategy, and the relative stereochemistries at the stereogenic centers in these substances were elucidated using X-ray analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products* / chemistry
  • Cyclization
  • Esters

Substances

  • boneratamide A
  • Biological Products
  • Esters