Saxitoxin (1, STX) 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 analytical STX 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 conditions utilizing PTSA as a catalyst proceeded with a useful level of yield.

Studies directed toward the total synthesis of saxitoxin: Addition of 1,3-dihydro-2H-imidazol-2-one to aldehydes

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.