Synthesis of C14-Desmethylene Corialactone D and Discovery of Inhibitors of Nerve Growth Factor Mediated Neurite Outgrowth

An asymmetric synthesis of C14-desmethylene corialactone D is described on the basis of strategic application of a metallacycle-mediated annulative cross-coupling reaction, a Still [2,3]-Wittig rearrangement, and Morken’s hydroxyl-directed diboration reaction. While representing a convenient approac...

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Bibliographic Details
Published in:Organic letters 2019-05, Vol.21 (9), p.3193-3197
Main Authors: Leon, Robert M, Ravi, Divya, An, Jennifer S, del Genio, Carmen L, Rheingold, Arnold L, Gaur, Arti B, Micalizio, Glenn C
Format: Article
Language:English
Subjects:
Alkaloids - chemical synthesis
Alkaloids - pharmacology
Animals
Lactones - chemical synthesis
Lactones - pharmacology
Nerve Growth Factor - antagonists & inhibitors
Neuronal Outgrowth - drug effects
PC12 Cells
Rats
Sesquiterpenes - chemical synthesis
Sesquiterpenes - pharmacology
Structure-Activity Relationship
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Summary:An asymmetric synthesis of C14-desmethylene corialactone D is described on the basis of strategic application of a metallacycle-mediated annulative cross-coupling reaction, a Still [2,3]-Wittig rearrangement, and Morken’s hydroxyl-directed diboration reaction. While representing a convenient approach to access novel compositions of matter inspired by the sesquiterpenoid natural product class (including classic natural product synthesis targets including the picrotaxanes and dendrobine), these studies have led to the discovery of natural product-inspired agents that inhibit nerve growth factor (NGF)-mediated neurite outgrowth in PC-12 cells.
ISSN:1523-7060
1523-7052
DOI:10.1021/acs.orglett.9b00921