4-Homopyrazofurin and an acyclic analogue

Article abstract of DOI:10.1016/0008-6215(93)80096-W

The synthesis of 4-hydroxymethyl-3(5)-(β-D-ribofuranosyl)pyrazole-5(3)-carboxamide (2, 4-homopyrazofurin) is described via a pathway that commences with the dipolar cycloaddition reaction of 2,5-anhydro-3,4,6-tri-O-benzyl-1-deoxy-1-diazo-D-allitol (4) and methyl 4-benzyloxy-2-butynoate (5). Preparation of 3(5)-[(2-hydrox,-ethoxy)methyl]-4-(hydroxymethyl)pyrazole-5(3)-carboxa mide (3) as a derivative of 2 possessing the truncated acyclic side chain of acyclovir has been accomplished in a similar manner beginning with the reaction of 5 with 1-diazo-2-[(2-benzyloxy)ethoxy]ethane (13). Neither compound 2 nor 3 showed any in vitro antiviral activity against human immunodeficiency virus (HIV-1), sandfly fever, Punta Toro, Japanese encephalitis, yellow fever, Venezuelan equine encephalomyelitis, and vaccinia viruses. Both compounds were also nontoxic. These results suggest that direct bonding of the hydroxyl group to the pyrazole ring is important for pyrazofurin based agents to demonstrate biological activity. The synthesis of 4-hydroxymethyl-3(5)- (β-D-ribofuranosyl)pyrazole-5(3)-carboxamide (2, 4-homo-pyrazofurin) is described via a pathway that commences with the dipolar cycloaddition reaction of 2,5-anhydro- 3,4,6-tri-O-benzyl-1-deoxy-1-diazo-D-allitol (4) and methyl 4-benzyloxy-2-butynoate (5). Preparation of 3(5)-[(2-hydrox,-ethoxy)methyl ]-4-(hydroxymethyl)pyrazole-5(3)-carboxamide (3) as a derivative of 2 possessing the truncated acyclic side chain of acyclovir has been accomplished in a similar manner beginning with the reaction of 5 with 1-diazo-2-[(2-benzyloxy)ethoxy]ethane (13). Neither compound 2 nor 3 showed any in vitro antiviral activity against human immunodeficiency virus (HIV-1), sandfly fever, Punta Toro, Japanese encephalitis, yellow fever, Venezuelan equine encephalomyelitis, and vaccinia viruses. Both compounds were also nontoxic. These results suggest that direct bonding of the hydroxyl group to the pyrazole ring is important for pyrazofurin based agents to demonstrate biological activity.