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General Synthesis Route to Benanomicin‐Pradimicin Antibiotics
Author(s) -
Tamiya Minoru,
Ohmori Ken,
Kitamura Mitsuru,
Kato Hirohisa,
Arai Tadamasa,
Oorui Mami,
Suzuki Keisuke
Publication year - 2007
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200700863
Subject(s) - stereocenter , stereochemistry , chemistry , regioselectivity , total synthesis , ring (chemistry) , acetal , stereoselectivity , moiety , diol , aldehyde , glycosylation , enantioselective synthesis , organic chemistry , catalysis , biochemistry
A general approach to the regio‐ and stereoselective total synthesis of the benanomicin‐pradimicin antibiotics (BpAs) is described. Construction of the aglycon has been achieved by 1) the diastereoselective ring‐opening of a biaryl lactone by using ( R )‐valinol as a chiral nucleophile and 2) the stereocontrolled semi‐pinacol cyclization of the aldehyde acetal by using SmI 2 in the presence of BF 3 ⋅ OEt 2 and a proton source to afford the ABCD tetracyclic monoprotected diol. This strategy enabled us to control the two stereogenic sites in the B ring (C‐5 and C‐6) and the regioselective introduction of the carbohydrate moiety. The ABCD tetracycle could serve as an ideal platform for the divergent access to various BpAs. The amino acid ( D ‐alanine) was introduced onto the ABCD tetracycle. Glycosylation was promoted by the combination of Cp 2 HfCl 2 and AgOTf (1:2 ratio). Construction of the E ring followed by deprotection completed the first total synthesis of benanomicin A ( 2 a ), benanomicin B ( 2 b ), and pradimicin A ( 1 a ). The route is flexible enough to allow the synthesis of other congeners differing in their amino acid and carbohydrate moieties.