Shivajirao L. Gholap, Indian Institute of Technology Delhi, New Delhi, and colleagues have performed the first asymmetric total synthesis of (+)-isostreptenol III (pictured). (+)-Isostreptenol III is a metabolite isolated from the organic extract of the terrestrial fungus Penicillium purpurogenum MM. This bioactive compound contains a diene unit and two contiguous stereocenters, of which one is a quaternary stereocenter. Until now, there had been no total synthesis of (+)-isostreptenol III to confirm its structure.
The team started from commercially available D-ribose, which was converted to a lactol, followed by the stereoselective installation of hydroxymethyl group and the introduction of an aldehyde group. Further key steps were a diastereoselective Wittig olefination and the introduction of an epoxide group (pictured below, MOM = methoxymethyl). Finally, the team synthesized (+)-isostreptenol III using an epoxide opening with the Grignard reagent methyl magnesium bromide in the presence of copper(I) iodide.
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Based on spectroscopic data, the team revised the absolute stereochemistry of the isolated natural product from the proposed (3R,4S)-(+)-isostreptenol III to 3R,4R-(+)-isostreptenol III. This was confirmed by synthesis of its enantiomer 3S,4S-(–)-isostreptenol III, which has an optical rotation that is in excellent agreement with that of the isolated natural (+)-isostreptenol, but with the opposite sign.
- First total synthesis and structure revision of (+)-Isostreptenol III,
Kapil Sharma, Naresh Surineni, Anu Dalal, Shivajirao L Gholap,
Eur. J. Org. Chem. 2021.
https://doi.org/10.1002/ejoc.202100655
