De novo asymmetric syntheses of (+)-goniothalamin, (+)-goniothalamin oxide, and 7,8-bis-epi-goniothalamin using asymmetric allylations

Abstract

A highly enantio-and diastereoselective approach to either enantiomer of (+)-goniothalamin, (+)-goniothalamin oxide and 7,8-bis-epi-goniothalamin oxide has been developed from achiral cinnamyl alcohol or cinnamaldehyde. The asymmetry of the synthesis was installed by means of a Krische or Leighton allylation. The remaining stereochemistry was installed by a diastereoselective epoxidation.

Diastereoselective Allylation of Carbonyl Compounds and Imines: Application to the Synthesis of Natural Products

“…An expeditious synthesis of (+)-goniothalamin and (+)-goniothalamin oxide was developed by O’Doherty and Harsh starting from cinnamaldehyde . Goniothalamin was isolated from the bark of Cryptocarya caloneura and possesses potent cytotoxicity toward a range of cancer cell lines .…”

Organic Synthesis Involving Iridium-Catalyzed Oxidation

“…Thus, the reaction is quite practical. In fact, O’Doherty used this allylation method in the synthesis of (+)-goniothalamin . The allylation is also applicable to furan methanol derivatives .…”

Metathetic Synthesis of Common and Medium-Sized Lactones: The State of the Art

“…Its most simple but still strongly bioactive representative is goniothalamin 55, first extracted from Cryptocarya caloneura, which is a powerful antitumor agent without significant side effects on benign cells. Recently, this compound was made by an asymmetric synthesis of its acrylate precursor 56, which undergoes a subsequent RCM catalyzed by G1 (Scheme 21) [109].…”