Cholecystokinin antagonist, synthesis

Amine (S)-(+)-97 is needed for the synthesis of a gastrointestinal hormone antagonist, Merck s cholecystokinin antagonist 96, by acylation with indole-2-carboxylic acid. 

Utilizing the Eguchi aza-Wittig protocol Snider et al. achieved the total synthesis of the more complex antibiotic (-)-asperUcin 20, known also for its potent cholecystokinin antagonist activity [76-79] (Scheme 21) [242]. L-Tryptophan-derived benzodiazepinedione 94 is converted into the fused quinazolinone 95. 

Boden, P.R. et al. (1993) Cholecystokinin dipeptoid antagonists Dest, synthesis, and anxiolytic profile of some novel CCKA and CCKB selective aird mixed CCKA/CCKB antagonists. / Med. Chem.. 36. 552-565. 

G. Ratcliffe, Targeted molecular diversity, design and development of non-peptide antagonists for cholecystokinin and tachykinin receptors, Immunopharmacology 1996, 33, 68-72 D.C. Horwell, W. Howson, G.S. Ratcliffe, H.M.G. Willems, The design of dipeptide helical mimetics the synthesis, tachykinin receptor affinity and conformational analysis of... 

For the synthesis of cholecystokinin-B receptor antagonists by Lowe III and coworkers [70], the amino benzazepin-2-one (47) was resolved into single stereoisomers by the protocol shown in Scheme 5.21 (for clarity, only single stereoisomers depicted). The notable feature in this instance is the selective removal of the L-phenylalanine auxiliary by Edman degradation in the presence of additional amide linkages. 

In the synthesis of Cholecystokinin-B receptor antagonists, a benzodiazepin intermediate bearing an isocyanato group plays a key role. It is prepared from the corresponding amine 423 by carbonylation with phosgene in 98% yield [292]. 

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