Synthesis of 5-(7-Hydroxyheptyl)-1,2-dithiolan-3-one 1-Oxide,a Core Functionality of Antibiotic Leinamycin

5-(7-Hydroxyheptyl)-1,2-dithiolan-3-one 1-oxide was designed and synthesized in our laboratories that contain the heterocycle of 1,2-dithiolan-3-one 1-oxide, a reactive core of antibiotic leinamycin. In addition, the activated ester of 5-(7-hydroxyheptyl)-1,2-dithiolan-3-one 1-oxide was prepared, which presumably is useful for coupling this DNA-cleaving functionality to certain DNA-binding agents.     

Incorporation of the bioactive moiety of leinamycin into thymidine

A simple synthesis of 1,2-dithiolan-3-ones from α,β-unsaturated thiophenyl esters has been elaborated. With the aim of introducing the biologically active 1,2-dithiolan-3-one-1-oxide moiety of leinamycin into a nucleoside, the method was successfully applied to thymidine-5^′-aldehyde.     

Studies on the synthesis of DNA-damaging part of leinamycin: regioselectivity in Ti(OiPr)4 mediated opening of hydroxy epoxides with carboxylic acids

The preparation of the key intermediate in the synthesis of the DNA damaging fragment of the anticancer antibiotic leinamycin starting from geraniol is described. The synthetic sequence involves the building of a quaternary asymmetric center through kinetic resolution through Sharpless epoxidation followed by the regioselective opening of the resultant enantiomerically pure hydroxyepoxide and intramolecular Wittig-Horner olefination.