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Convenient synthesis of 3,4-methano-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and its derivatives as doubly constrained nonproteinogenic amino acid derivatives

par Czombos, József;Aelterman, Wim;Tkachev, Alexey;Martins, José;Tourwe, Dirk ;Péter, Antal;Tóth, Géza;Fülöp, Ferenc;De Kimpe, Norbert
Référence Journal of organic chemistry, 65, 18, page (5469-5475)
Publication Publié, 2000-09

Article révisé par les pairs

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Résumé :

Three strategies for the synthesis of the novel, doubly constrained, 3,4-methano-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and its derivatives were evaluated. Only cyclocondensation of the mono(triphenyl)phosphonium salt derived from 1,2-bis(bromomethyl)benzene with N-alkoxycarbonyloxamates in 1,2-dimethoxyethane in the presence of potassium carbonate and subsequent cyclopropanation with dimethylsulfoxonium methylide in dimethyl sulfoxide furnished suitable O- and N-protected derivatives of 3,4-methano-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid in a convenient way. A detailed 2D DQF-COSY and 2D NOESY NMR analysis of the rotational isomerism of the latter bicyclic amino acid derivatives was performed. Various O- and N-protection protocols were worked out to afford access to a whole range of new derivatives of the title amino acid, suitable for peptide synthesis.