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Synthesis of O ‐linked Cyclitol Analogues of Gilvocarcin M and Antibacterial Activity
Author(s) -
Sharif Ehesan U.,
Shi Pei,
O'Doherty George A.
Publication year - 2021
Publication title -
israel journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.908
H-Index - 54
eISSN - 1869-5868
pISSN - 0021-2148
DOI - 10.1002/ijch.202100015
Subject(s) - chemistry , stereochemistry , cyclitol , glycoside , biosynthesis , disaccharide , sugar , combinatorial chemistry , organic chemistry , biochemistry , gene , receptor , inositol
Two unnatural regioisomeric glycosylated Gilvocarcin analogues were proposed as model compounds to study the origin behind the biosynthetic development of the Gilvocarcins, a class of bioactive C ‐aryl glycoside natural products. More specifically, the origins behind the proposed O ‐ to C ‐glycoside migration in the evolution of the biosynthesis for these classes of Angucycline antibiotic natural products. For stability reasons a 5a‐carbasugar motif was used to mimic the sugar portion of the molecule and of synthetic ease the proposed abiotic rearrangement move the sugar analogue along with its O ‐glycoside linkage. The two proposed regioisomeric analogues were synthesized by a regio‐divergent synthetic pathway and featured a Mitsunobu‐like invertive cyclictolization reaction to install the carbasugar motif. The two regioisomeric Gilvocarcin analogues were evaluated as antibiotic with Gilvocarcin M as a control. Only one of the two isomers showing weak antibiotic activity as compared to Gilvocarcin M.