Keith Michael Devries

The preparation of β-substituted amines from mixtures of epoxide opening products via a common aziridinium ion intermediate

Abstract Here we describe a one-pot synthesis of a series of β-substituted amines as single enantiomers from an initial regioisomeric mixture of styrene oxide ring-opening products. We also report the isolation and characterization of a key β-chloro intermediate and provide additional insight into the mechanism of the reported alkylations. These results require that the reaction proceeds through a common aziridinium ion intermediate on two separate occasions in order to account for the observed overall net retention of configuration in proceeding from ( S )-styrene oxide to the desired β-substituted amine products.

Efficient synthesis of the κ-opioid receptor agonist CJ-15,161: four stereospecific inversions at a single aziridinium stereogenic center

Abstract An efficient four-step sequence has been developed for the synthesis of the κ-opioid receptor agonist CJ-15,161. The process features four consecutive regioselective and stereospecific inversions at a single aziridinium stereogenic center, which leads to overall retention of stereochemistry, in a single operation. The chemistry is straightforward, practical and amenable to large-scale synthesis.

Synthesis of trovafloxacin using various (1α,5α,6α)-3-azabicyclo[3.1.0]hexane derivatives

Trovafloxacin, a novel broad spectrum antibacterial, contains the unusual (1α,5α,6α)-3-azabicyclo[3.1.0]hexane ring system. The prototype of the industrial synthesis of this ring system and possible mechanistic pathways to exclusive formation of the exo or 6α-nitro derivative 4 are described, which leads to the key 6α-nitro-3-azabicyclo[3.1.0]hexane intermediate 10. The synthesis of 6α-amino-3-azabicyclo[3.1.0]hexane 16 and useful protected exo 6-amino derivatives 15 and 17 follows from 10. These can be coupled with the 7-chloronaphthyridone 18 to yield protected trovafloxacin compounds 20–22 in good yield. The ethyl ester of trovafloxacin 21 can also be accessed from the product of coupling 19, derived from 18 and the exo 6-nitro-3-azabicyclo[3.1.0]hexane compound 12. Removal of protecting groups from 20–22 with methanesulfonic acid yields trovafloxacin mesylate from which trovafloxacin zwitterion 1 can be liberated with base treatment. Zwitterion 1 can also be prepared directly from 16 tosylate salt and naphthyridone-2-carboxylic acid 26.