Fiesselmann thiophene

The Fiesselmann thiophene synthesis involves the condensation reaction of thioglycolic acid derivatives with a,P-acetylenic esters, which upon treatment with base results in the formation of 3-hydroxy-2-thiophenecarboxyIic acid derivatives. 

The structure of sitaxsentan (2) is also somewhat modular and was divided into three building blocks—namely the phenyl ring, the central thiophene, and the aminoisoxazole. The isoxazole subunit 33 can be prepared by the reaction of hydroxylamine with butynenitrile (31) to form the heterocycle,30 followed by chlorination with NCS.22 The thiophene ring can be formed using a Fiesselmann thiophene synthesis starting from... 

Further investigation of anti-tubulin agents by Romagnoli et al. led to the development of a modified Fiesselmann thiophene synthesis to produce 3-amino-2-(3,4,5-trimethoxybenzoyl)-5-aryl-thiophenes. " The a-mercapto-ketone anion was generated in situ by treating 0-ethyI-5-[2-oxo-2-(3,4,5-trimethoxyphenyl)-ethyl]dithiocarbonate with piperidine. Reaction of the a-mercapto anion with P-chloro-arylcinnamonitriles under thermal conditions afforded the desired thiophene. Much like the 2-amino derivatives, these 3-amino-2-(3,4,5-trimethoxy-benzoyl)-5-aryl-thiophenes were shown to be potent anti-proliferation and anti-tubulin agents as well. 

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