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Total synthesis of (-)-CP2-disorazole C1.

ABSTRACT: The total synthesis of a bis-cyclopropane analog of the antimitotic natural product (-)-disorazole C(1) 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. IC(50) determinations of (-)-CP(2)-disorazole C(1) 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.

SUBMITTER: Hopkins CD

PROVIDER: S-EPMC3160746 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Total synthesis of (-)-CP2-disorazole C1.

Hopkins Chad D CD Schmitz John C JC Chu Edward E Wipf Peter P

Organic letters 20110708 15

The total synthesis of a bis-cyclopropane analog of the antimitotic natural product (-)-disorazole C(1) 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. IC(50) determinations of (-)-CP(2)-disorazole C(1) in human colon cancer cell lines indicated low nanomolar cytotoxic properties. Accordingly, this synthetic bioisostere represents the first biologically active disorazole analog not cont ...[more]

PMID: 21739942

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Catalytic Z-selective cross-metathesis in complex molecule synthesis: a convergent stereoselective route to disorazole C1.

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Mitotic slippage in non-cancer cells induced by a microtubule disruptor, disorazole C1.

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