Reductive and nucleophilic activation products of dynemicin A with methyl thioglycolate. A rational mechanism for DNA cleavage of the thiol-activated dynemicin A

The reaction products of methyl thioglycolate with dynemicin A, dynemicin H and dynemicin S, were isolated by HPLC purification and identified spectroscopically. The major product, dynemicin H (C 30 H 23 NO 9 ), was determined to a C-8 hydrogen analogue of dynemicins L and N in which the enediyne core is aromatized. The minor product, dynemicin S(C 33 H 27 No 11 S), is an adduct of methyl thioglycolate at the C-8 position. By using NADPH instead of methyl thioglycolate, the reaction with dynemicin A also gives the same major product (dynemicin H). The formation of dynemicins H and S provides a rationale for the reductive and nucleophilic activations of dynemicin A