Total Synthesis of an Atropisomer of the Schisandra Triterpenoid Schiglautone A

Abstract

Adiastereoselective approach for the total synthesis of an unusual atropisomer of the Schisandratriterpenoid (AE)schiglautone Ai sd escribed. The efficient synthetic strategy features three key transformations:1)two sequential titanium-(III)-catalyzed radical cyclization/homologation reactions to construct the trans-fused [6,7] bicycle as well as install the quaternary carbons at C10 and C14 with the desired stereochemistry;2 )a Claisen rearrangement followed by ar ingclosing metathesis to forge the strained nine-membered ring; and 3) as ubstrate-controlled Michael addition to enable the introduction of the C17 side-chain with good diastereoselectivity.

Unusually cyclized triterpenoids: occurrence, biosynthesis and chemical synthesis

“…This natural product appears as an atropisomer and the diastereoselective synthesis was achieved by Ding and coworkers. Preparation of the tricyclic enone 392 (Scheme 26), 123 which carries the entire cyclic carbon skeleton, commenced with the regioselective epoxidation of trans -nerolidol ( 381 ) followed by acetylation to furnish epoxypolyprene 382 . Furthermore, titanium( iii )-catalyzed radical cyclization 124 of 382 afforded the desired trans -fused bicyclic precursor 383 .…”

“…This natural product appears as an atropisomer and the diastereoselective synthesis was achieved by Ding and coworkers. Preparation of the tricyclic enone 392 (Scheme 26),123 which carries the entire cyclic carbon skeleton, commenced with the regioselective epoxidation of trans-nerolidol (381) followed by acetylation to furnish epoxypolyprene 382. Furthermore, titanium(III)-catalyzed radical cyclization124 of 382 afforded the desired trans-fused bicyclic precursor 383. mCPBA mediated epoxidation of ring double bond of 383 followed by inversion of the C-3 hydroxyl group through oxidation (Ley-Griffith oxidation) and reduction (Meerwein-Ponndorf-Verley reduction) protocols, and benzylic protection of the resulting hydroxyl group generated epoxide 385.The lactone 387 was constructed from 385 by employing the Gansäuer protocol,125 which upon reduction, Swern oxidation, subsequent chemoselective Grignard addition and silylation, provided bicyclic ketone 388.…”

Total Synthesis of Terpenes and Their Biological Significance: A Critical Review

“…Desilylation of alcohol (522) with TBAF yielded (523) and (524) in a 78% yield. (±)-atrop-Schiglautone A (523) is a diastereomeric atropisomer of (±)-schiglautone A (524) (Scheme 31) [163].…”