In 2014, Sugawara and coworkers reported unique alkylated hydroquinone, violaceoids A (1) and B (2), which were isolated from a culture broth of Aspergillus violaceofuscus Gasperini coexisted with moss. Although a lot of bioactive hydroquinones had been reported, there were few reports of the cytotoxic hydroquinone compound that has the hydroxymethyl group and linear alkyl group. Additionally, the absolute configuration of violaceoid B was not determined. So we decided to synthesize 1 and 2 for the porpose to determine the absolute configuration of violaceoid B and to evaluate the bioactivity of the synthetic violaceoids A, B and their analogs. The first total synthesis of violaceoid A (1), a cytotoxic compound, and the first asymmetric total synthesis of (S)- and (R)-violaceoid B ((S)-2, (R)-2) are reported. The precursor (3) was accessed by desymmetrization of a substituted quinol moiety, and the racemic secondary alcohol (rac-4) was kinetically resolved using a chiral nucleophilic catalyst. The asymmetric synthesis of (S)- and (R)-violaceoid B elucidated the absolute configuration of the naturally occurring violaceoid B. The evaluation of the cytotoxicity of synthetic violaceoids and their analogs was carried out.

Total synthesis and evaluating bioactivity of violaceoids A, B and their analogs

2019 Fall National Meeting

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