A Biosynthetic Proposal for Ring Formation in the Antitumor Agent Halichomycin. Asymmetric Synthesis of the AB-Carbon Backbone of Halichomycin

A biosynthetic proposal for ring formation in the antitumor agent halichomycin is presented in which macrocyclization of the putative prehalichomycin intermediate 1 is the first step. Compound 2 then undergoes dehydration to the α-keto N-acylimine 3 followed by tandem nucleophilic addition of the C(...

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Published inOrganic letters Vol. 4; no. 6; pp. 897 - 900
Main Authors Hale, Karl J, Dimopoulos, Paschalis, Cheung, Maxine L. F, Frigerio, Mark, Steed, Jonathan W, Levett, Philip C
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 21.03.2002
Amer Chemical Soc
Subjects
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Carbon - chemistry
Chemistry
Chemistry, Organic
Heterocyclic Compounds, 4 or More Rings - chemistry
Heterocyclic Compounds, 4 or More Rings - metabolism
Physical Sciences
Science & Technology
OLEFINS
HYDROBORATION
AMIDES
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Summary:A biosynthetic proposal for ring formation in the antitumor agent halichomycin is presented in which macrocyclization of the putative prehalichomycin intermediate 1 is the first step. Compound 2 then undergoes dehydration to the α-keto N-acylimine 3 followed by tandem nucleophilic addition of the C(16)-hydroxyl to form the hemimacrolactam. A stereospecific Michael ring closure and enol protonation complete C-ring assembly. So far, synthetic efforts toward 1 have resulted in 8.
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ISSN:1523-7060
1523-7052
DOI:10.1021/ol017266a