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Synthesis and Cytotoxicity of Ring C‐Functionalized Derivatives of the Marine Natural Product (–)‐Dibromophakellstatin
Author(s) -
Moldovan RareşPetru,
Zöllinger Michael,
Jones Peter G.,
Kelter Gerhard,
Fiebig HeinzHerbert,
Lindel Thomas
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201101175
Subject(s) - chemistry , ring (chemistry) , natural product , pyrrolidine , stereochemistry , cytotoxicity , derivative (finance) , tunicate , diastereomer , regioselectivity , combinatorial chemistry , organic chemistry , catalysis , ecology , biochemistry , economics , financial economics , in vitro , biology
A structure–activity relationship study of ring C‐functionalized derivatives of the cytotoxic marine natural product(–)‐dibromophakellstatin from the sponge Phakellia mauritiana is reported. Functionalization of the pyrrolidine ring was achieved starting from the hydroxy derivative by conversion to the triflate followed by etherification by epimerizing nucleophilic substitution. We identified (12 R )‐dibromo‐12‐hydroxyphakellstatin as the most cytotoxic derivative, which exhibited an average IC 50 value of 1.4 μ M against a panel of twelve human cancer cell lines. However, the 12 S diastereomer was inactive. Dehydrophakellstatin was synthesized as the first example of a phakellin skeleton with an unsaturated ring C.