Synthesis of methylated phenylalanines via hydrogenolysis of corresponding 1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acids
- 12 January 1994
- journal article
- research article
- Published by Wiley in International Journal of Peptide and Protein Research
- Vol. 43 (1) , 62-68
- https://doi.org/10.1111/j.1399-3011.1994.tb00376.x
Abstract
A new method of synthesizing ortho-methylated phenylalanines has been developed. Phenylalanines with at least one free ortho-position undergo a Pictet-Spengler cyclization with formaldehyde followed by hydrogenolytic splitting of the endocyclic benzylic C--N bond of 1,2,3,4-tetrahydroisoquinolines and afford corresponding ortho-methyl derivatives. Repeating this reaction sequence on the ortho-substituted phenylalanines yielded ortho,ortho-disubstituted derivatives, and para-substituted phenylalanines yielded ortho,para-disubstituted analogs. Our modified method of cyclization preserved the configuration at the chiral center: hydrogenolysis, on the other hand, led to racemization. Incorporation of the methylated phenylalanines into position 2 of oxytocin led to, in the case of the D-isomers, potent uterotonic inhibitors.Keywords
This publication has 23 references indexed in Scilit:
- Conformationally biased analogs of oxytocinInternational Journal of Peptide and Protein Research, 1992
- A Facile Synthesis of 1,2,3,4-Tetrahydro-7-hydroxyisoquinoline-3-carboxylic Acid, a Conformationally Constrained Tyrosine AnalogueSynthesis, 1992
- Conformationally restricted analogs of oxytocin; stabilization of inhibitory conformation†International Journal of Peptide and Protein Research, 1990
- Synthesis and biological properties of vasopressin analogues containing 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acidCollection of Czechoslovak Chemical Communications, 1990
- Design and synthesis of somatostatin analogs with topographical properties that lead to highly potent and specific .mu. opioid receptor antagonists with greatly reduced binding at somatostatin receptorsJournal of Medicinal Chemistry, 1988
- Conformational and biological analysis of α-MSH fragment analogues with sterically constrained amino acid residuesCollection of Czechoslovak Chemical Communications, 1988
- Noninvasive continuous monitoring of solid-phase peptide synthesis by acid-base indicatorCollection of Czechoslovak Chemical Communications, 1988
- Synthesis of novel angiotensin converting enzyme inhibitor quinapril and related compounds. A divergence of structure-activity relationships for non-sulfhydryl and sulfhydryl typesJournal of Medicinal Chemistry, 1986
- Oxytocin analogues with inhibitory properties, containing in position 2 a hydrophobic amino acid of D-configurationCollection of Czechoslovak Chemical Communications, 1985
- Steric Course and Specificity of α-Chymotrypsin-catalyzed Reactions. IJournal of the American Chemical Society, 1962