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A Natural Product Inspired Tetrahydropyran Collection Yields Mitosis Modulators that Synergistically Target CSE1L and Tubulin
Author(s) -
Voigt Tobias,
GerdingReimers Claas,
Ngoc Tran Tuyen Thi,
Bergmann Sabrina,
Lachance Hugo,
Schölermann Beate,
Brockmeyer Andreas,
Janning Petra,
Ziegler Slava,
Waldmann Herbert
Publication year - 2013
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201205728
Subject(s) - tetrahydropyran , prins reaction , tubulin , mitosis , natural product , chemistry , microbiology and biotechnology , vinca , vinca alkaloid , microtubule , aldehyde , biochemistry , biology , stereochemistry , organic chemistry , pharmacology , genetics , ring (chemistry) , chemotherapy , vincristine , cyclophosphamide , catalysis
A Prins cyclization between a polymer‐bound aldehyde and a homoallylic alcohol served as the key step in the synthesis of tetrahydropyran derivatives. A phenotypic screen led to the identification of compounds that inhibit mitosis (as seen by the accumulation of round cells with condensed DNA and membrane blebs; see picture). These compounds were termed tubulexins as they target the CSE1L protein and the vinca alkaloid binding site of tubulin.