Bioinspired total synthesis of boneratamides A–C

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.