Convenient synthesis of 3,4-methano-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and its derivatives as doubly constrained nonproteinogenic aminoacid derivatives
J. Czombos et al., Convenient synthesis of 3,4-methano-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and its derivatives as doubly constrained nonproteinogenic aminoacid derivatives, J ORG CHEM, 65(18), 2000, pp. 5469-5475
Three strategies for the synthesis of the novel, doubly constrained, 3,4-me
thano-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and its derivatives
were evaluated. Only cyclocondensation of the mono(triphenyl)phosphonium sa
lt derived from 1,2-bis(bromomethyl)benzene with N-alkoxycarbonyloxamates i
n 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-tet
rahydroisoquinoline-3-carboxylic acid in a convenient way. A detailed 2D DQ
F-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 derivat
ives of the title amino acid, suitable for peptide synthesis.