Synthesis of methylated phenylalanines via hydrogenolysis of corresponding 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids. Synthesis and biological activity of oxytocin analogs with methylated phenylalanines in position 2
Language English Country Denmark Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Phenylalanine chemistry MeSH
- Isoquinolines chemistry MeSH
- Protein Conformation MeSH
- Rats MeSH
- Methylation MeSH
- Molecular Sequence Data MeSH
- Molecular Structure MeSH
- Oligopeptides chemical synthesis MeSH
- Oxytocin analogs & derivatives chemistry MeSH
- Rats, Wistar MeSH
- Amino Acid Sequence MeSH
- Stereoisomerism MeSH
- Tetrahydroisoquinolines * MeSH
- Uterus drug effects MeSH
- Hydrogen chemistry MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid MeSH Browser
- Phenylalanine MeSH
- Isoquinolines MeSH
- Oligopeptides MeSH
- Oxytocin MeSH
- Tetrahydroisoquinolines * MeSH
- Hydrogen MeSH
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.
References provided by Crossref.org
