Convenient synthesis of 3,4-methano-1,2,3, 4-tetrahydroisoquinoline-3-carboxylic acid and its derivatives as doubly constrained nonproteinogenic amino acid derivatives.
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.
Czombos
J
J
Department of Organic Chemistry, Faculty of Agricultural and Applied Biological Sciences, University of Gent, Coupure Links 653, B-9000 Gent, Belgium.
Aelterman
W
W
Tkachev
A
A
Martins
J C
JC
Tourwé
D
D
Péter
A
A
Tóth
G
G
Fülöp
F
F
De Kimpe
N
N
D000596:Amino Acids / Q000737:chemistry*; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D013057:Spectrum Analysis; D044005:Tetrahydroisoquinolines
C413845:3,4-methano-1,2,3,4,-tetrahydroisoquinoline-3-carboxylic acid; D000596:Amino Acids; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines