Evolution of a Short and Stereocontrolled Synthesis of (+)-7,20-Diisocyanoadociane

A full account of the development of a concise and highly stereoselective synthesis of (+)-7,20-diisocyanoadociane (DICA)-a structurally complex isocyanoditerpene with potent antiplasmodial activity-is described. The strategy that evolved relies on the rapid construction of unsaturated tricyclic pre...

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Bibliographic Details
Published in:Journal of organic chemistry Vol. 87; no. 2; pp. 1398 - 1420
Main Authors: Roosen, Philipp C., Karns, Alexander S., Ellis, Bryan D., Vanderwal, Christopher D.
Format: Journal Article
Language:English
Published: WASHINGTON Amer Chemical Soc 21.01.2022
Subjects:
Chemistry
Chemistry, Organic
Nitriles
Physical Sciences
Pyrenes
Science & Technology
Stereoisomerism
REARRANGEMENT
ORGANOCERIUM REAGENTS
PODOCARPIC ACID
CONJUGATE REDUCTION
FORMAL TOTAL-SYNTHESIS
CYCLIC ETHERS
BIRCH REDUCTION
AROMATIC-COMPOUNDS
LITHIUM-AMINE
MICHAEL ADDITION
ISSN:0022-3263, 1520-6904, 1520-6904
Online Access:Get more information
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Summary:A full account of the development of a concise and highly stereoselective synthesis of (+)-7,20-diisocyanoadociane (DICA)-a structurally complex isocyanoditerpene with potent antiplasmodial activity-is described. The strategy that evolved relies on the rapid construction of unsaturated tricyclic precursors designed to undergo stereocontrolled Birch reductions and a subsequent bay ring formation to generate the isocycloamphilectane core. This report is divided into three sections: (1) a description of the initial strategy and the results that focused our efforts on a single route to the DICA core, (2) a discussion of the precise choreography needed to enable a first-generation formal synthesis of (+/-)-DICA, and (3) the execution of a 13-step second-generation synthesis of (+)-DICA that builds on important lessons learned from the first-generation effort.
Bibliography:NIH RePORTER
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ISSN:0022-3263
1520-6904
1520-6904
DOI:10.1021/acs.joc.1c02700