Stereocontrolled Synthesis of the Quinaldic Acid Macrocyclic System of Thiostrepton

An efficient construction of the quinaldic acid macrocycle (see picture) of the antibiotic thiostrepton is based on state‐of‐the‐art asymmetric synthesis. The 27‐membered macrocycle includes a quinaldic acid moiety, a thiazole ring, and a dehydroalanine unit. The key steps in the convergent assembly...

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Bibliographic Details
Published inAngewandte Chemie International Edition Vol. 41; no. 11; pp. 1937 - 1940
Main Authors Nicolaou, K. C., Safina, Brian S., Funke, Christian, Zak, Mark, Zécri, Frédéric J.
Format Journal Article
LanguageEnglish
Published Weinheim WILEY-VCH Verlag GmbH 03.06.2002
WILEY‐VCH Verlag GmbH
Wiley
Subjects
Anti-Bacterial Agents - chemical synthesis
Anti-Bacterial Agents - chemistry
antibiotics
asymmetric synthesis
Chemistry
Chemistry, Multidisciplinary
macrocycles
Macrocyclic Compounds - chemistry
natural products
Physical Sciences
Quinolines - chemistry
Science & Technology
Stereoisomerism
Thiostrepton - chemical synthesis
Thiostrepton - chemistry
total synthesis
THIOPEPTIN
MICROCOCCIN
DEHYDROPIPERIDINE
SKELETON
FAMILY
PEPTIDE ANTIBIOTICS
natural products
ARENE
EPOXIDES
asymmetric synthesis
macrocycles
HIGHLY ENANTIOSELECTIVE EPOXIDATION
ASYMMETRIC EPOXIDATION
total synthesis
antibiotics
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Summary:An efficient construction of the quinaldic acid macrocycle (see picture) of the antibiotic thiostrepton is based on state‐of‐the‐art asymmetric synthesis. The 27‐membered macrocycle includes a quinaldic acid moiety, a thiazole ring, and a dehydroalanine unit. The key steps in the convergent assembly included: a) amide bond formation, b) esterification, and c) macrolactamization.
Bibliography:ark:/67375/WNG-GMNWCRC8-G
ArticleID:ANIE1937
istex:EDC9081542859D077B6BEAE9753C46A62ABF642D
We thank Drs. D. H. Huang and G. Suizdak for NMR spectroscopic and mass spectrometric assistance, respectively, as well as Mike Sertic (University of California, San Diego) for experimental assistance. Financial support for this work was provided by The Skaggs Institute for Chemical Biology, the National Institutes of Health (USA), fellowships from The Skaggs Institute for Research (to M.Z. and F.Z.), and grants from Abbott, Amgen, Array Biopharma, Boehringer‐Ingelheim, Glaxo, Hoffmann‐LaRoche, DuPont, Merck, Novartis, Pfizer, and Schering Plough.
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:1433-7851
1521-3773
DOI:10.1002/1521-3773(20020603)41:11<1937::AID-ANIE1937>3.0.CO;2-Y