In:
Angewandte Chemie, Wiley, Vol. 128, No. 3 ( 2016-01-18), p. 1042-1047
Abstract:
We report a concise asymmetric synthesis of rakicidin A, a macrocyclic depsipeptide that selectively inhibits the growth of hypoxic cancer cells and stem‐like leukemia cells. Key transformations include a diastereoselective organocatalytic cross‐aldol reaction to build the polyketide portion of the molecule, a highly hindered ester fragment coupling reaction, an efficient Helquist‐type Horner—Wadsworth—Emmons (HWE) macrocyclization, and a new DSC‐mediated elimination reaction to construct the sensitive APD portion of rakicidin A. We further report the preparation of a simplified structural analogue (WY1) with dramatically enhanced hypoxia‐selective activity.
Type of Medium:
Online Resource
ISSN:
0044-8249
,
1521-3757
DOI:
10.1002/ange.201509926
Language:
English
Publisher:
Wiley
Publication Date:
2016
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505868-5
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506609-8
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514305-6
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505872-7
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1479266-7
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505867-3
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506259-7
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