Puromycin analogs. Studies on ribosomal binding with diastereomeric carbocyclic puromycin analogs

Article abstract of DOI:10.1021/jm00252a003

A direct and convenient route to the antimicrobial carbocyclic puromycin analog, 6 dimethylamino 9 [(R) [(2R) hydroxy (3R) (p methoxyphenyl L alanylamino)]cyclopentyl]purine is described. Epoxidation of 3 acetamidocyclopentene gave exclusively cis 3 acetamido 1,2 epoxycyclopentane. Opening of the epoxide with NaN₃, followed by reduction of the resulting azido alcohol 5, gave a high yield of 2α acetamido 5β aminocyclopentan 1α ol. 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 1α ol. Resolution at an early point allows for the conversion of these to a wide variety of diastereomeric aminoacyl derivatives. Studies on protein synthesis inhibition with diastereomeric carbocyclic puromycin analogs indicate that 2 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.