Bayesian Self-Optimization for Telescoped Continuous Flow Synthesis.

The optimization of multistep chemical syntheses is critical for the rapid development of new pharmaceuticals. However, concatenating individually optimized reactions can lead to inefficient multistep syntheses, owing to chemical interdependencies between the steps. Herein, we develop an automated continuous flow platform for the simultaneous optimization of telescoped reactions.

Structure-Activity Relationship Studies of Cyclopropenimines as Enantioselective Brønsted Base Catalysts.

We recently demonstrated that chiral cyclopropenimines are viable Brønsted base catalysts in enantioselective Michael and Mannich reactions. Herein, we describe a series of structure-activity relationship studies that provide an enhanced understanding of the effectiveness of certain cyclopropenimines as enantioselective Brønsted base catalysts. These studies underscore the crucial importance of dicyclohexylamino substituents in mediating both reaction rate and enantioselectivity.

A two-directional approach to pyrrolizidines: total syntheses and biological evaluation of alkaloid cis-223B and (±)-xenovenine.

Total syntheses of alkaloid cis-223B and xenovenine are reported in 3 and 4 steps respectively using a two-directional synthesis/triple reductive amination strategy, and their neurotoxic properties assessed.

Combining two-directional synthesis and tandem reactions: a short formal synthesis of halichlorine.

A short and efficient synthesis of an advanced intermediate (1) in the Clive route to halichlorine has been achieved in 12 steps and 13.2% yield by a combined two-directional synthesis/tandem reaction strategy.

[Nasal and auricular inverted papillomas].

We report a rare case of an inverted papilloma with an unusual clinical course: development in the middle ear, multiples recurrences, and invasion of the temporal bone.