Synthesis of novel peptidyl adenosine antibiotic analogs

Nucleosides Nucleotides Nucleic Acids. 2014;33(2):53-63. doi: 10.1080/15257770.2013.866243.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemical synthesis*
  • Adenosine / chemistry
  • Adenosine / pharmacology
  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry
  • Antimalarials / pharmacology
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Humans
  • Molecular Structure
  • Parasitic Sensitivity Tests

Substances

  • Antimalarials
  • Antineoplastic Agents
  • Adenosine