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
Jazyk angličtina Země Dánsko Médium print
Typ dokumentu srovnávací studie, časopisecké články, práce podpořená grantem
- MeSH
- fenylalanin chemie MeSH
- isochinoliny chemie MeSH
- konformace proteinů MeSH
- krysa rodu Rattus MeSH
- metylace MeSH
- molekulární sekvence - údaje MeSH
- molekulární struktura MeSH
- oligopeptidy chemická syntéza MeSH
- oxytocin analogy a deriváty chemie MeSH
- potkani Wistar MeSH
- sekvence aminokyselin MeSH
- stereoizomerie MeSH
- tetrahydroisochinoliny * MeSH
- uterus účinky léků MeSH
- vodík chemie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid MeSH Prohlížeč
- fenylalanin MeSH
- isochinoliny MeSH
- oligopeptidy MeSH
- oxytocin MeSH
- tetrahydroisochinoliny * MeSH
- vodík 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.
Citace poskytuje Crossref.org
