synthesis and transformations of di-endo-3-aminobicyclo-[2.2.2]oct-5-ene-2-carboxylic acid derivatives合成和转换di-endo-3-aminobicyclou2014u2014(2.2.2)oct-5-ene-2-carboxylic酸衍生品.pdf

Molecules 2011, 16, 7691-7705; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Synthesis and Transformations of di-endo-3-Aminobicyclo- [2.2.2]oct-5-ene-2-carboxylic Acid Derivatives Márta Palkó 1, Pál Sohár 2 and Ferenc Fülöp 1,* 1 Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Eötvös utca 6, Hungary 2 Institute of Chemistry, Eötvös Lóránd University, H-1518 Budapest, POB 32, Hungary * Author to whom correspondence should be addressed; E-Mail: fulop@pharm.u-szeged.hu; Tel.: +36-62-545-562; Fax: +36-62-545-705. Received: 18 July 2011; in revised form: 24 August 2011 / Accepted: 6 September 2011 / Published: 7 September 2011 Abstract: all-endo-3-amino-5-hydroxybicyclo[2.2.2]octane-2-carboxylic acid (13) and all- endo-5-amino-6-(hydroxymethyl)bicyclo[2.2.2]octan-2-ol (10) were prepared via dihydro- 1,3-oxazine or γ-lactone intermediates by the stereoselective functionalization of an N- protected derivative of endo-3-aminobicyclo[2.2.2]oct-5-ene-2-carboxylic acid (2). Ring closure of β-amino ester 4 resulted in tricyclic pyrimidinones 15 and 16. The structures, stereochemistry and relative configurations of the synthesized compounds were determined by IR and NMR. Keywords: hydroxy-β-amino acids; cyclization; heterocycles; retro Diels-Alder reaction; microwave 1. Introduction The synthesis of non-natural α-amino acids is currently an important synthetic challenge in view of their increasing role in chemistry and biology. Among th