1. Synthesis of Novel Peptidyl Adenosine Antibiotic Analogs
- Author
-
Robert C. Reynolds and Omar Moukha-Chafiq
- Subjects
chemistry.chemical_classification ,Adenosine ,Molecular Structure ,Stereochemistry ,Chemistry ,Carboxylic acid ,Antineoplastic Agents ,Biological activity ,Peptide ,General Medicine ,Biochemistry ,Photo-reactive amino acid analog ,Antimalarials ,Hydrolysis ,Parasitic Sensitivity Tests ,Cell Line, Tumor ,Genetics ,medicine ,Humans ,Molecular Medicine ,Moiety ,Nucleoside ,medicine.drug - Abstract
A small library of peptidyl adenosine antibiotic analogs was synthesized, under the Pilot Scale Library Program of the NIH Roadmap initiative, from 2',3'-O-isoproylideneadenosine-5'-carboxylic acid 2 in excellent yield. The coupling of the amino terminus of L-2-aminophenylbutyric methyl ester to a free 5'-carboxylic acid moiety of 2 followed by sodium hydroxide treatment led to carboxylic acid analog 4. Hydrolysis of this latter gave unprotected nucleoside analog 5. Intermediate 4 served as the precursor for the preparation of novel peptidyl adenosine analogs 6-18 in good yields and high purity through peptide coupling reactions to diverse amine derivatives. No marked anticancer and antimalaria activity was noted on preliminary cellular testing; however these analogs should be useful candidates for other types of biological activity.
- Published
- 2014