Synthesis, Stereochemistry and Antiparasitic Activity of Derivatives of (4R)-4,6-Dihydroxy-N-methyl-1,2,3,4-tetrahydroisoquinoline
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...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
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Wiley - V C H Verlag GmbH & Co. KGaA
2017
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| Online Access: | http://hdl.handle.net/20.500.11937/52521 |
| _version_ | 1848758947317547008 |
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| author | Cullen, Danica Pengon, J. Rattanajak, R. Chaplin, J. Kamchonwongpaisan, S. Massera, C. Mocerino, Mauro Rohl, Andrew |
| author_facet | Cullen, Danica Pengon, J. Rattanajak, R. Chaplin, J. Kamchonwongpaisan, S. Massera, C. Mocerino, Mauro Rohl, Andrew |
| author_sort | Cullen, Danica |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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 1H 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 IC50 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 IC50 values in the low micromolar range. |
| first_indexed | 2025-11-14T09:52:05Z |
| format | Journal Article |
| id | curtin-20.500.11937-52521 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:52:05Z |
| publishDate | 2017 |
| publisher | Wiley - V C H Verlag GmbH & Co. KGaA |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-525212017-09-13T15:48:32Z Synthesis, Stereochemistry and Antiparasitic Activity of Derivatives of (4R)-4,6-Dihydroxy-N-methyl-1,2,3,4-tetrahydroisoquinoline Cullen, Danica Pengon, J. Rattanajak, R. Chaplin, J. Kamchonwongpaisan, S. Massera, C. Mocerino, Mauro Rohl, Andrew 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 1H 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 IC50 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 IC50 values in the low micromolar range. 2017 Journal Article http://hdl.handle.net/20.500.11937/52521 10.1002/slct.201602036 Wiley - V C H Verlag GmbH & Co. KGaA restricted |
| spellingShingle | Cullen, Danica Pengon, J. Rattanajak, R. Chaplin, J. Kamchonwongpaisan, S. Massera, C. Mocerino, Mauro Rohl, Andrew Synthesis, Stereochemistry and Antiparasitic Activity of Derivatives of (4R)-4,6-Dihydroxy-N-methyl-1,2,3,4-tetrahydroisoquinoline |
| title | Synthesis, Stereochemistry and Antiparasitic Activity of Derivatives of (4R)-4,6-Dihydroxy-N-methyl-1,2,3,4-tetrahydroisoquinoline |
| title_full | Synthesis, Stereochemistry and Antiparasitic Activity of Derivatives of (4R)-4,6-Dihydroxy-N-methyl-1,2,3,4-tetrahydroisoquinoline |
| title_fullStr | Synthesis, Stereochemistry and Antiparasitic Activity of Derivatives of (4R)-4,6-Dihydroxy-N-methyl-1,2,3,4-tetrahydroisoquinoline |
| title_full_unstemmed | Synthesis, Stereochemistry and Antiparasitic Activity of Derivatives of (4R)-4,6-Dihydroxy-N-methyl-1,2,3,4-tetrahydroisoquinoline |
| title_short | Synthesis, Stereochemistry and Antiparasitic Activity of Derivatives of (4R)-4,6-Dihydroxy-N-methyl-1,2,3,4-tetrahydroisoquinoline |
| title_sort | synthesis, stereochemistry and antiparasitic activity of derivatives of (4r)-4,6-dihydroxy-n-methyl-1,2,3,4-tetrahydroisoquinoline |
| url | http://hdl.handle.net/20.500.11937/52521 |