Synthetic Study on Sespendole, an Indole Sesquiterpene Alkaloid: Stereo­controlled Synthesis of the Sesquiterpene Segment Bearing All Requisite Stereogenic Centers

Abstract

Stereocontrolled synthesis of a sesquiterpene segment with all requisite stereogenic centers for sespendole has been achieved. Synthetic features of our strategy involve (1) highly stereoselective [2,3]-Wittig rearrangement to obtain sterically congested quaternary carbon and (2) isomerization of a spiro epoxide into aldehyde with Cp 2 TiCl 2 /Mn in a highly stereoselective manner.

Applications of the Wittig–Still Rearrangement in Organic Synthesis

“…[76] Its relative stereochemistry was determined by spectroscopic methods,e xcept for the stereochemistry of the epoxide at C-31. During his approach to the racemate,N ishikawa reported the synthesis of the sesquiterpene unit 255, [77] one of the building blocks envisioned in the convergent assembly of the natural product as shown in Scheme 36. Intermediates 254 and 255 would lead to 253 via Sonogashira coupling, [78] and the indole moiety could then be accessed from 253 by means of Castro-type indole synthesis.…”

“…Sespendole (AE)-( 252)and the key building blocks for the synthesis reported by Nishikawa. [77] Scheme37. Nishikawa's synthesis of racemic sesquiterpene unit of sespendole (AE)-( 255).…”

“…Nishikawa's synthesis of racemic sesquiterpene unit of sespendole (AE)-( 255). [77] Angewandte Chemie Reviews Wittig-Still rearrangement, which proceeded to 261 in 79 % yield. This provides aparticularly powerful demonstration of the true synthetic utility of the Wittig-Still rearrangement: an ew quaternary center was formed with ah igh level of diastereoselectivity (261 was obtained as as ingle isomer), in an equatorial configuration.…”

Anwendungen der Wittig‐Still‐Umlagerung in der organischen Synthese

“…[80] 255). [77] Schema 36. Sespendol( AE)-( 252)u nd die Schlüsselbausteine der Synthese nach Nishikawa.…”

“…Sespendol( AE)-( 252)u nd die Schlüsselbausteine der Synthese nach Nishikawa. [77] [83] Fukuyama berichtete 2012 eine Totalsynthese des tetracyclischen Sesquiterpens (À)-Anisatin (279). [84] Die Schlüsselschritte der Synthese waren die asymmetrische rhodium- Das Problem der facialen Selektivitätwurde schließlich mithilfe des Intermediats 307 gelçst, das in Ring Ak eine Stereozentren auf-Schema 40.…”