Puromycin Analogs. Studies on Ribosomal Binding with Diastereomeric Carbocyclic Puromycin Analogs

Robert Vince, Susan Daluge

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

A direct and convenient route to the antimicrobial carbocyclic puromycin analog, 6-dimethylamino-9-[(n)-[(2n)- hydroxy-(3P)-(p-methoxyphenyl-L-alanylamino)]cyclopentyl]purine (la), is described. Epoxidation of 3-acetamidocyclopentene (3) gave exclusively cis-3-acetamido-1,2-epoxycyclopentane (4). Opening of the epoxide with NaN3, followed by reduction of the resulting azido alcohol 5, gave a high yield of 2α-acetamido-5β-aminocyclopentan-la-ol (6). This amine was easily resolved via tartrate formation. Introduction of the purine moiety by standard methods gave the enantiomeric carbocyclic aminonucleosides (-)- and (+)-2α-acetamido-5β-(6-dimethylamino-9-purinyl)- cyclopentan-la-ol (10a and 10b). Resolution at an early point allows for the conversion of 10a and 10b to a wide variety of diastereomeric aminoacyl derivatives. Studies on protein synthesis inhibition with diastereomeric carbocyclic puromycin analogs indicate that two distinct types of protein synthesis inhibitors may have been developed— series a which are peptidyl transferase substrates, and series b which are peptidyl transferase inhibitors.

Original languageEnglish (US)
Pages (from-to)578-583
Number of pages6
JournalJournal of Medicinal Chemistry
Volume17
Issue number6
DOIs
StatePublished - Jun 1 1974

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Peptidyl Transferases
Puromycin
Puromycin Aminonucleoside
Sodium Azide
Protein Synthesis Inhibitors
Epoxy Compounds
Amines
Alcohols
Proteins
carbocyclic puromycin
purine
tartaric acid

Cite this

Puromycin Analogs. Studies on Ribosomal Binding with Diastereomeric Carbocyclic Puromycin Analogs. / Vince, Robert; Daluge, Susan.

In: Journal of Medicinal Chemistry, Vol. 17, No. 6, 01.06.1974, p. 578-583.

Research output: Contribution to journalArticle

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