삭시톡신 합성을 위한 연구: 1,3-dihydro-2H-imidazol-2-one의 알데히드에 첨가반음

Abstract

Saxitoxin (STX, 1) is a highly toxic natural product, which is produced by several types of harmful dinoflagellates and accumulated in bivalves to intoxicate human being eventually. Due to the unique toxicity and the scarcity of analyticalSTX standard, development of a convenient synthetic pathway to this molecule has been an attractive project in the synthetic community. In this report, we disclose our efforts to synthesize the carbon framework of STX with a proper functionalization utilizing an addition reaction of imidazol-2-one 2 with an aldehyde. The imidazolone 2 was prepared from 1-bromo-5-chloropentan-2-one in 5 steps. Mannich-type addition of 2 with benzylamine and ethyl glyoxalate 3 was investigated under various acidic conditions to find optimal reaction conditions. In most cases, the reactivities of 2 as a nucleophile were insufficient to produce the desired product in satisfactory levels of yields. However, the reaction conditionsutilizing PTSA as a catalyst proceeded with a useful level of yield.