Details
| Original language | English |
|---|---|
| Pages (from-to) | 529-538 |
| Number of pages | 10 |
| Journal | Synthesis (Germany) |
| Volume | 50 |
| Issue number | 3 |
| Early online date | 24 Nov 2017 |
| Publication status | Published - Feb 2018 |
Abstract
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.
Keywords
- biological evaluation, hidden Markov model, natural products, stereoselective synthesis, structure elucidation
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
- Organic Chemistry
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In: Synthesis (Germany), Vol. 50, No. 3, 02.2018, p. 529-538.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - The Structure Elucidation of Haprolid
AU - Li, Jun
AU - Xing, Jun
AU - Lücke, Daniel
AU - Lübken, Dennis
AU - Millbrodt, Lucas
AU - Plentz, Ruben R.
AU - Kalesse, Markus
N1 - Funding information: We thank the Hannover School for Biomolecular Drug Research (HSBDR) for the financial support to L.M.
PY - 2018/2
Y1 - 2018/2
N2 - 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.
AB - 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.
KW - biological evaluation
KW - hidden Markov model
KW - natural products
KW - stereoselective synthesis
KW - structure elucidation
UR - http://www.scopus.com/inward/record.url?scp=85035766149&partnerID=8YFLogxK
U2 - 10.1055/s-0036-1591836
DO - 10.1055/s-0036-1591836
M3 - Article
AN - SCOPUS:85035766149
VL - 50
SP - 529
EP - 538
JO - Synthesis (Germany)
JF - Synthesis (Germany)
SN - 0039-7881
IS - 3
ER -