The Structure Elucidation of Haprolid

The assignment of two stereocenters of the natural product haprolid through the application of a profile hidden Markov model (HMM) and its confirmation through total synthesis of the natural product and of two of its diastereomers are reported. The structure elucidation of this polyketide-peptide hy...

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Bibliographic Details
Published inSynthesis (Stuttgart) Vol. 50; no. 3; pp. 529 - 538
Main Authors Li, Jun, Xing, Jun, Luecke, Daniel, Luebken, Dennis, Millbrodt, Lucas, Plentz, Ruben R., Kalesse, Markus
Format Journal Article
LanguageEnglish
Published STUTTGART Thieme Medical Publishers 01.02.2018
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
TRANSFORMATION
natural products
REVISION
hidden Markov model
biological evaluation
NATURAL-PRODUCTS
BIOSYNTHESIS
stereoselective synthesis
SYNTHASES
SECONDARY METABOLITE
structure elucidation
CHLORINATION
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Summary:The assignment of two stereocenters of the natural product haprolid through the application of a profile hidden Markov model (HMM) and its confirmation through total synthesis of the natural product and of two of its diastereomers are reported. The structure elucidation of this polyketide-peptide hybrid natural product is a telling showcase of how difficult it can be to determine the absolute configuration of isolated stereocenters and the benefits of a gene cluster analysis for structure determination. The key steps of the synthesis are a selective epoxidation of a terminal olefin and the stereodivergent macrolactonization strategy. Furthermore, the biological evaluation of all products showed that all diastereomers are potent inhibitors of hepatocellular carcinoma cell lines.
ISSN:0039-7881
1437-210X
DOI:10.1055/s-0036-1591836