Evidence for aminoglycoside participation in thiol activation of neocarzinostatin chromophore. Synthesis and reactivity of the epoxy dienediyne core

The reaction of the chromophore subunit (1) of the natural antibiotic neocarzinostatin with methyl thioglycolate produces an NMR-observable intermediate, assigned as 2, which decays with a half-life of ~2 h at -38 °C to form the putative biradical 3. While the latter rearrangement is striking, perhaps no less so is the thiol addition step (1 → 2), which occurs readily at -70 °C in acetic acid-tetrahydrofuran (1:9, t_(1/2) ≃ 1.5 h, 0.2 thiol). Reported herein are (1) the assembly of the full core functionality of neocarzinostatin chromophore in a synthetic system and (2) the preparation of a nonbasic derivative of the chromo-phore itself. Experiments with these synthetic materials provide strong evidence that thiol activation of 1 is facilitated dramatically participation of the carbohydrate amino group as an base.