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Synthesis of 3,4‐Fused γ‐Lactone‐γ‐Lactam Bicyclic Moieties as Multifunctional Synthons for Bioactive Molecules
Author(s) -
Shaameri Zurina,
Azib Nur Aini,
Mohamat Mohd Fazli,
Hamzah Ahmad Sazali
Publication year - 2016
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.2433
Subject(s) - chemistry , bicyclic molecule , diastereomer , synthon , ketone , sodium borohydride , lactam , stereochemistry , lactone , hydrolysis , nuclear magnetic resonance spectroscopy , organic chemistry , catalysis
A short approach for the synthesis of 3,4‐fused γ‐lactone‐γ‐lactam bicyclic systems ( 1 ) in diastereomeric mixtures from chiral D ‐alanine methyl ester hydrochloride is described. The key step towards lactonisation is the reduction of the carbonyl ketone of the 5 R ‐configured 3,5‐dimethylpyrrolidine‐2,4‐dione diastereomers ( 8 ) via sodium borohydride in the presence of hydrochloric acid . With the presence of ethyl acetyl functionality at C3‐position, ester hydrolysis of 8 occurred concomitantly with keto reduction leading to lactonisation and eventually affording the anticipated (3 S ,4 S , 5R ), (3 R ,4 R , 5R ), (3 R ,4 S , 5R ) and (3 S ,4 R , 5R ) bicyclic moieties. The formation of the fused systems was confirmed by mass spectroscopy (MS) and nuclear magnetic resonance (NMR) analyses.