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Synthesis of DOHNAA, a Mycobacterium tuberculosis Cholesterol CD Ring Catabolite and FadD3 Substrate
Author(s) -
Stubbing Louise A.,
Lott J. Shaun,
Dawes Stephanie S.,
Furkert Daniel P.,
Brimble Margaret A.
Publication year - 2015
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.201500698
Subject(s) - catabolite repression , chemistry , mycobacterium tuberculosis , cholesterol , enzyme , mycobacterium , biochemistry , alkylation , stereochemistry , bacteria , tuberculosis , gene , biology , mutant , medicine , genetics , pathology , catalysis
DOHNAA ( 2 ) is a key catabolite in the Mycobacterium tuberculosis (Mtb) cholesterol degradation pathway. The CoA ester of 2 has been implicated in regulation of gene transcription that is ultimately responsible for degradation of the C and D rings of cholesterol. A synthetic route to 2 is reported here, by a key DMSO‐mediated Morita–Bayliss–Hillman‐type alkylation of the Hajos–Parrish dione. As DOHNAA has to date only been available from microbial sources in very small quantities, the synthesis described will enable further studies of the enzymes involved in cholesterol degradation in Mtb and facilitate ongoing structure–activity studies based on this compound scaffold.