Libing Yu

Strategies for the synthesis of novel indole alkaloid-based screening libraries for drug discovery

A series of diverse indole-based chemotypes were synthesized from β-tetrahydrocarboline (β-THC) scaffolds prepared from commercially and readily available tryptamines and α-ketoesters. Diversity can be generated within these chemotypes through the following strategies: (a) appendage of substituents to the β-THC scaffold, prepared in situ or as a template, through further elaboration and (b) skeletal modifications to the β-THC scaffold via ring forming or ring breaking reactions. The strategies described here are amenable to high throughput solution-phase parallel synthesis, providing access to novel indole-based screening libraries for drug discovery.