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Design and Novel Synthesis of a Nonpeptide Cholecystokynin Antagonist(PDF)

《南京理工大学学报》(自然科学版)[ISSN:1005-9830/CN:32-1397/N]

Issue:
2000年02期
Page:
177-180
Research Field:
Publishing date:

Info

Title:
Design and Novel Synthesis of a Nonpeptide Cholecystokynin Antagonist
Author(s):
WeiYunyang JosephP.Konopelski ①
School of Chemical Engineering,NUST,Nanjing 210094)
Keywords:
pharmaceutical chemistry organic synthesis asparagine cholecystokynin condensat ion
PACS:
O629
DOI:
-
Abstract:
Cholecystoky nin( cck) is a poly pept ide hormone w hich plays an important role in the digest ive t ract w here it predominant ly interact s w ith cck-A receptor, and also in the central nervous system where it essentially act s as a neurotransmitter throug h cck-B type receptors. Some non-pept ide compounds also possess the aff inity for cck receptors and become the subject of intense research. Herein the design and sy nthesis of similar compounds of the non-pept ide cck antagonist ( + ) RP66803 containing tet rahydropyrimidinone ring instead of pyrrolidine ring w ere reported. T he sy nthesis started w ith asparagine t-butyl ester, w hich reacted w ith benzaldehyde toform an imine. Treat ing the imine w ith glycine chloride led to coupling and cyclization to form an intermediate, 3-pheny-l 4-aminomethylcarbony-l 5-t-buty-l carbonyl tetrahydropy rimidinone, and then reacted w ith m-tolylisocyanate to form the desired product in 42 % overall yield( based on asparagine t-buty l ester) .

References:

1 Nadzan A M, Kerw in J F. Cholecystokinin agonists and antago nists. Annu Rep Med Chem, 1991,26: 191~ 200
2 Haddad M, Imogai H, Larcheveque M. T he first enant ioselective synt hesis of the cis- 2- carbox y- 5-phenylpyr rolidine. J Org Chem, 1998, 63( 16) : 5 680~ 5 683
3 Manfre F, Pulicani J P. Enantiospecific synthesis and absolute configuration of ( + ) RP66803 a new non-peptide cck antagonist. Tetrahedro n Asymmetry , 1994, 5( 2) : 235~ 238
4 Konopelski J P, Filonova L K, Olmstead M M. Dipeptide surro gates containing asparagine- derived tetrahydropy rimidines. J Am Chem Soc, 1997, 119: 4 305~ 4 306
5 Konopelski J P, Wei Y, Olmstead M M. Dipeptide surrogates containing asparagine- der ived tetr ahydropy rimidines: structur e and amide rotomer stereochemistr y o f a proline mimic. J Org Chem1999, 64( 14) : 5 148~ 5 151

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Last Update: 2013-03-25