Tryprostatins A and B were isolated from the fermentation broth of Aspergillus fumigatus BM939 by Osada in 1995. Tryprostatins act as a microtubule inhibitor which can prevent cell cycle progression at the G2/M phase through a distinctive mechanism by the interaction between microtubule-assisted proteins (MAP) and the C-terminal end of tubulin. Recently the tryprostatin has shown more potent cytotoxic activity than etoposide against three human cancer cell lines. The poor abundance of tryprostatins in nature and long, low-yielding synthesis has limited their development as viable anti-cancer therapeutics, while on the other hand, their interesting biological activity and simple structure has drawn attention from the synthetic community and several total syntheses have been reported. The concise synthesis of tryprostatins B has been achieved through a key asymmetric phase-transfer catalyzed (PTC) reaction providing protected tryptophan derivatives for incorporation into natural products of the tryprostatin family. Our previous work on asymmetric tryptophans has been modified and optimized for C2-prenyl gramine salt, leading to the development of a route to these desirable natural products. This newly generated reaction has yielded as high as 92% ee and 32% overall yield.

Asymmetric phase-transfer catalyzed reaction of prenylated gramine salt: Synthesis of tryprostatin B

256th National Meeting (2018)

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