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Formal Synthesis of (−)‐Englerin A and Cytotoxicity Studies of Truncated Englerins
Author(s) -
Xu Jing,
CaroDiaz Eduardo J. E.,
Batova Ayse,
Sullivan Steven D. E.,
Theodorakis Emmanuel A.
Publication year - 2012
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201101021
Subject(s) - cytotoxicity , stereochemistry , ring (chemistry) , aldol condensation , enantioselective synthesis , chemistry , intramolecular force , cycloaddition , cancer cell lines , conjugate , combinatorial chemistry , cancer cell , catalysis , cancer , in vitro , biology , biochemistry , organic chemistry , mathematical analysis , mathematics , genetics
Abstract An efficient formal synthesis of (−)‐englerin A ( 1 ) is reported. The target molecule is a recently isolated guaiane sesquiterpene that possesses highly potent and selective activity against renal cancer cell‐lines. Our enantioselective strategy involved the construction of the BC ring system of compound 1 through a Rh II ‐catalyzed [4+3] cycloaddition reaction followed by subsequent attachment of the A ring through an intramolecular aldol condensation reaction. As such, this strategy allows the synthesis of truncated englerins. Evaluation of these analogues with the A498 renal cancer cell‐line suggested that the A ring of englerin is crucial to its antiproliferative activity. Moreover, evaluation of these analogues led to the identification of potent growth‐inhibitors of CEM cells with GI 50 values in the range 1–3 μ M .