The Synthesis and Reactivity of -Cyclized Bicyclomycin. Evidence of the Role of the C(1)-Triol Group in Bicyclomycin-Mediated Processes

Article abstract of DOI:10.1021/jo00045a041

The C(1) triol group in the antibiotic, bicyclomycin (1) has been proposed to play an integral role in the bonding of key protein nucleophiles to the distal C(5)-C(5a) terminal double bond in the drug.Evidence in support of this concept has been provided by the comparison of the reactivities of bicyclomycin (1), the -cyclized bicylomycin adduct 3, 2',3'-bicyclomycin acetonide (17), and the acetonide derivative of 3, 18, with sodium ethanethiolate.Significantly, 3 displayed enhanced reactivity versus 1, 17, and 18 in this transformation.The controlling factors for the increased reactivity of 3 have been discerned and the importance of the C(1') hydroxyl group delineated.Key kinetic parameters are reported for the treatment of both 3 and 17 with 2-mercaptopyridine.Structural details are provided for both C(5a) thiolate and amine adducts of 3.The importance of these findings in relation to the mode of action of bicyclomycin are briefly discussed.