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Synthesis, Stereochemistry and Antiparasitic Activity of Derivatives of (4 R )‐4,6‐Dihydroxy‐ N ‐methyl‐1,2,3,4‐tetrahydroisoquinoline
Author(s) -
Cullen Danica R.,
Pengon Jutharat,
Rattanajak Roonglawan,
Chaplin Jason,
Kamchonwongpaisan Sumalee,
Massera Chiara,
Mocerino Mauro,
Rohl Andrew L.
Publication year - 2017
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201602036
Subject(s) - chemistry , stereochemistry , derivative (finance) , tetrahydroisoquinoline , amine gas treating , selectivity , organic chemistry , financial economics , economics , catalysis
Condensation of phenylephrine with different aldehydes, under Pictet‐Spengler cyclisation conditions, afforded a series of tetrahydroisoquinoline derivatives as mixtures of cis/trans isomers. Single crystal X‐ray analysis of the dibenzoate derivative of one of the 4‐nitrophenyl isomers confirmed it to be the trans isomer. The conformation of the cis isomer was determined through computational experiments and comparison of the predicted and observed 1 H NMR spectra, particularly the magnitude of the coupling constants. Fourteen tetrahydroisoquinoline derivatives were then evaluated for their activity towards T. b. rhodesiense , two strains of P. falciparum , and mammalian cells. The most promising derivative, the undecyl derivative, showed good activity towards T. b. rhodesiense with an IC 50 value in the sub‐micromolar range and good selectivity over mammalian cells. The same derivative also showed activity against both strains of P. falciparum with IC 50 values in the low micromolar range.