Asymmetric Total Syntheses of Euphol and Tirucallol

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作   者：

Nicholson, Joshua M.;  Micalizio, Glenn C.; 

作者机构：

Dartmouth Coll; 

关键词：

REARRANGEMENT;  CHOLESTEROL;  TRITERPENOIDS;  STEROIDS;  LANOSTEROL; 

期刊名称：

Organic letters

i s s n：

1523-7060

年卷期：

2023 年 25 卷 30 期

页   码：

5687-5691

页   码：

摘   要：

Asymmetric de novo syntheses of eupholand tirucallolhave been accomplished by way of a concise sequence of chemical stepsfeaturing several modern stereoselective transformations. The preparativesolution described for these complex problems in natural product synthesisdeparts significantly from biomimetic polyene cyclization chemistry,which has been leveraged to address related tetracyclic triterpenoidtargets. In particular, a diastereoselective Friedel-Crafts-typecyclization was employed to establish a tetracycle bearing a stereodefinedquaternary center at C9 (steroid numbering) that provided access tointermediates of relevance for introducing the C10 and C14 quaternarycenters by sequential stereospecific 1,2-alkyl shifts (C9 & RARR;C10 and C15 & RARR; C14). Finally, the stereodefined C17 side chainwas introduced in a single step by late-stage stereoselective conjugateaddition to an intermediate possessing a D-ring enone. Notably, these de novo asymmetric syntheses are the first of their kind,providing completely synthetic access to enantiodefined euphane andtirucallane systems. Overall, each synthesis has been accomplishedin fewer than 20 linear chemical steps from a simple Hajos-Parrish-derivedketone through a sequence that features just 15 chromatographic operations.