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ChemInform Abstract: Synthesis of the Alkaloid Homaline in (.+-.) and Natural (S,S)-(-) Forms, Using Amination and Transamidative Ring Expansion in Liquid Ammonia

Authors :
Ab. Rasid Mat-Zin
Leslie Crombie
Raymond C. F. Jones
David Haigh
Source :
ChemInform. 24
Publication Year :
2010
Publisher :
Wiley, 2010.

Abstract

Synthesis of the alkaloid homaline in (±) and natural (S,S)-(–) forms is reported. Linking of 2-azacyclooctanone units either directly or successively using 1,4-dihalogenobutanes or 1,4-dihalogenobut-2-ynes is examined. (±)-5-Methyl-4-phenyl-1,5-diazacyclooctan-2-one is first made by a 2,2′-dithiodipyridine/triphenylphosphine-mediated cyclisation, and then by amination and transamidative ring expansion from N-(3-chloropropyl)-4-phenylazetidin-2-one in liquid ammonia, followed by N-methylation. Coupling through a 1,4-dihalogenobutane of either the N-methylated azalactam, or the unmethylated azalactam followed by methylation, gave homaline in (±) and meso forms.(R)-(–)-Phenylglycine was converted via(S)-β-phenyl-β-alanine into an (S)-β-lactam which was then alkylated with 1-bromo-3-chloropropane, and aminated and ring expanded in liquid ammonia. Coupling of the homochiral azalactam (2 mol) so formed with 1,4-dibromobutane, followed by N-methylation, gave (S,S)-(–)-homaline identical with the natural material.

Details

ISSN :
09317597
Volume :
24
Database :
OpenAIRE
Journal :
ChemInform
Accession number :
edsair.doi...........835b80138ffb70bc0c39699b63b4c98b