Thieme E-Journals - Synlett / Abstract

On Aug 1, 2012 Contributor(s): Philip Kocienski published: Synthesis of LY500307

Rhodium-Catalyzed Asymmetric 1,4-Addition and Its …

The potent and selective compounds 2 (WAY-163909)and 3 (vabicaserin) are agonists that exhibit high affinity(Ki of ∼10 and 3 nM, respectively)and good efficacy for 5HT2C (EC50 = 8 nM each)and have been characterized extensively in preclinical drug trials.,,−In orderto overcome the synthesis challenge of carbon-11 incorporationfor 2 and 3, [11C]formaldehydewas used in a Pictet–Spengler cyclization.

This new asymmetric transformation was subsequently applied in the asymmetric formal synthesis of the drug candidate Vabicaserin. Show Navigation Hide Navigation.

He graduated from Kyoto University in 1970

The synthesis of vabicaserin analogues bearing a quaternary center or spiro substitution at the 4-position has been studied via a [6π]-acrylanilide cyclization employing flow photochemistry in a mesoscale and microfluidic flow photoreactor. The method is also used to synthesize 4,4′-disubstituted tetrahydroquinolines and, furthermore, enables the first synthesis of (±)--vabicaserin.

21/12/2017 · Asymmetric Synthesis of Vabicaserin via Oxidative Multicomponent Annulation and Asymmetric Hydrogenation of a 3,4-Substituted Quinolinium Salt

Cycloalkenes with exocyclic acceptor substituents still remain challenging substrates for enantioselective rhodium-catalyzed 1,4-addition. Cycloalkene carbonitriles and carboxylates have been investigated, and a highly diastereo- and enantioselective protocol for 1,4-addition to cyclopentene and cycloheptene carbonitrile has been developed. This new asymmetric transformation was subsequently applied in the asymmetric formal synthesis of the drug candidate Vabicaserin.

1: Dziechciejewski WJ, Weber R, Sowada O, Boysen MM. Cycloalkene Carbonitriles in Rhodium-Catalyzed 1,4-Addition and Formal Synthesis of Vabicaserin.