Total synthesis of (-)-CP2-disorazole C1

Chad D. Hopkins; John C. Schmitz; Edward Chu; Peter Wipf

doi:10.1021/ol2015994

Total synthesis of (-)-CP₂-disorazole C₁

Chad D. Hopkins, John C. Schmitz, Edward Chu, Peter Wipf

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

The total synthesis of a bis-cyclopropane analog of the antimitotic natural product (-)-disorazole C₁ was accomplished in 23 steps and 1.1% overall yield. A vinyl cyclopropane cross-metathesis reaction generated a key (E)-alkene segment of the target molecule. IC₅₀ determinations of (-)-CP₂-disorazole C₁ in human colon cancer cell lines indicated low nanomolar cytotoxic properties. Accordingly, this synthetic bioisostere represents the first biologically active disorazole analog not containing a conjugated diene or polyene substructure element.

Original language	English (US)
Pages (from-to)	4088-4091
Number of pages	4
Journal	Organic Letters
Volume	13
Issue number	15
DOIs	https://doi.org/10.1021/ol2015994
State	Published - Aug 5 2011
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1021/ol2015994

Cite this

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AU - Schmitz, John C.

AU - Chu, Edward

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AB - The total synthesis of a bis-cyclopropane analog of the antimitotic natural product (-)-disorazole C1 was accomplished in 23 steps and 1.1% overall yield. A vinyl cyclopropane cross-metathesis reaction generated a key (E)-alkene segment of the target molecule. IC50 determinations of (-)-CP2-disorazole C1 in human colon cancer cell lines indicated low nanomolar cytotoxic properties. Accordingly, this synthetic bioisostere represents the first biologically active disorazole analog not containing a conjugated diene or polyene substructure element.

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