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Updated: Apr 16, 2026

From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Complete Structure and Total Synthesis of Streptospherin A, a Cancer Stem Cell Inhibitor
Taiki Suo1, Takefumi Kuranaga1, Saya Yoshida1
1Department of System Chemotherapy and Molecular Sciences, Division of Medicinal Frontier Sciences, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Kyoto, Japan.
Abstract:
Streptospherin A (1), isolated from the actinomycete Streptomyces sp. KUSC-240 strain, inhibits cancer stem cell sphere formation. The planar structure of 1 and the relative configurations of C3, C5, and C7 in the pyran ring were previously assigned as (3R*, 5S*, 7S*). However, the remaining relative stereochemistry and absolute configuration of 1 have not been determined because of limited sample availability. In this study, the relative configuration at C2 was established by synthesizing model compounds 15a/15b and comparing their NMR spectra with that of 1. The absolute configuration of 1 was then confirmed by total synthesis. Synthetic 1 exhibited inhibitory activity of cancer stem cell sphere formation equivalent to that of the natural 1.
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Structures of Carboxylic Acid Derivatives
Carboxylic acid derivatives contain an acyl group attached to a heteroatom such as chlorine, oxygen, or nitrogen. The carbonyl carbon and oxygen are both sp2-hybridized with an unhybridized p orbital.
The three sp2 orbitals of the carbonyl carbon form three σ bonds, one each with the carbonyl oxygen, the α carbon, and the heteroatom, whereas the other two sp2 orbitals of the carbonyl oxygen are occupied by the lone pairs. Further, the...