A Stereocontrolled Annulation of the Taccalonolide Epoxy Lactone onto the Molecular Framework of trans-Androsterone.

A robust and scalable route to the taccalonolide skeleton starting from trans-androsterone is presented. The synthesis features a cyclic hydroboration carbonylation reaction, which effectively establishes the trans-hydrindane DE ring junction in a remarkable annulation reaction, as well as a Claisen rearrangement and a catalytic Ullmann-type cyclization. This work is part of a larger effort to uncover new clinical candidates from the taccalonolide class of anticancer agents through advances in chemical synthesis.

Conjugate-base-stabilized Brønsted acids: catalytic enantioselective Pictet-Spengler reactions with unmodified tryptamine.

A conjugate-base-stabilized Brønsted acid facilitates catalytic enantioselective Pictet-Spengler reactions with unmodified tryptamine. The chiral carboxylic acid catalyst is readily assembled in just two steps and enables the formation of ß-carbolines with up to 92% ee. Achiral acid additives or in situ Boc-protection facilitate catalyst turnover.

Kinetic resolution of amines via dual catalysis: remarkable dependence of selectivity on the achiral cocatalyst.

A dual-catalysis/anion-binding approach with a chiral hydrogen bonding (HB) catalyst and an achiral nucleophilic cocatalyst was applied to the kinetic resolution of amines. Out of a structurally diverse collection of 22 nucleophilic species, 4-di-n-propylaminopyridine emerged as the most efficient cocatalyst, allowing for the kinetic resolution of benzylic amines with s-factors of up to 67.