Robert A. Earl

Synthesis of Pyrrolo[2,3-d]pyrimidines that are Structurally Related to Methylated Guanosines from tRNA and the Nucleoside Q Analogs, PreQ0 and PreQ1

Abstract The N-3- and N-2-methylated analogs of several 5-substituted 2 amino-7-(β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidin-4-ones were synthesized from 5-cyano-2,4-dichloro-7-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine (10). These compounds are analogs of nucleoside Q that are methylated in a manner similar to some of the naturally occurring methylated guanosines. Present Address: 663 Moorpark Way, Mountain View, CA 94041 Present Address: Pharmacy Building, Purdue University, West Lafayette, IN 47907-1333 Present Address: Department of Chemist, North Island College 2300 Ryan Road, Courtenay, BC V9N 8N6, Canada

Pyrazolopyrimidine nucleosides. Part III. Synthesis of 1- and 2-(β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidines from pyrazole nucleo-side derivatives

The trimethylsilyl derivative (6) of 3-(3,3-dimethyl-1-triazeno)pyrazole-4-carboxamide (4) was condensed with 2,3,5-tri-O-acetyl-D-ribofuranosyl bromide (7) to give a mixture of nucleosides that were subsequently established as isomers rather than anomers. Removal of the blocking groups from one of the isomers furnished 5-(3,3-di-methyl-1-triazeno)-1-(β-D-ribofuranosyl)pyrazole-4-carboxamide (12) which was catalytically hydrogenated to afford the pyrazole analogue, 5-amino-1-(β-D-ribofuranosyl)pyrazole-4-carboxamide (13), of AICA riboside. Ring closure of (13) with formic acid-acetic anhydride followed by treatment with base furnished a mixture of nucleosides which were separated and characterized as 1-(β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4-one (16; allopurinol riboside) and 6-methyl-1-(β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4-one (17). The other isomer (8) furnished 3-(3,3-dimethyl-1-triazeno)-1-(β-D-ribofuranosyl)pyrazole-4-carboxamide (11) which was converted by a similar series of reactions into 2-(β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidin-4-one (15).