Anila Bhan

A Short Synthesis of a Novel Ring-Expanded Purine and Its Nucleoside Analogue Containing the Imidazo[4,5-e][1,3]diazepine Ring Skeleton with Multiple Amino Substituents Attached to the 7-Membered Ring

Abstract The synthesis of 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine (1) and its nacleoside analogue (6) are reported. The heterocycle was prepared in a single step by condensation of 4,5-dicyanoimidazole with guanidine. The 5,7-fused ring structure of 1 was distinguished from the other possible 5:5-fused isomer 2 by preparing the 15N-labeled heterocycle (1∗) and exploring its 15N-1H coupling patterns in both 1H and 15N NMR spectra. These spectral patterns also enabled establishment of the triamino tautomeric form of 1 as assigned. Compound 1, a novel ring-expanded (“fat”) analogue of purine, is anticipated to be planar and aromatic as predicted by molecular modeling. The 1 -benzyl analogue (4), a protocol for the ribosyl analogue 6, was similarly prepared from 1-benzyl-4,5-dicyanoimidazole. The nucleoside 6 was prepared by the modified Vorbrulggen ribosylation of 1. The position of ribosylation was unequivocally established by an unambiguous synthesis of 6 from condensation of 1 -(2′,3′,5-tri-O-benzoyl-β...

The Synthesis of Novel Regioisomeric Ring-Expanded Xanthine Nucleosides Containing The 5:7-Fused Imidazo[4,5-e][1,2,4]Triazepine Ring System

Abstract The syntheses of novel regioisomeric ring-expanded purine nucleosides containing the imidazo[4,5-e][1,2,4]triazepine nucleus are reported. The glycosylation of the heterocycle 3,4,6,7-tetrahydroimidazo[4,5-e][1,2,4]triazepine-5,8-dione (2a) by the stannic chloride procedure gave nucleosides 3 and 4, with the sugar moiety attached at the 7-and 3-positions of the heterocycle, respectively. On the other hand, the mercuric cyanide procedure for glycosylation of 2a yielded nucleosides 4 and 5, with the sugar attached at the 1-position in the latter. In either procedure, 4 was the minor isomer and was obtained only in trace amounts. While debenzoylation of 3 and 5 provided the respective parent nucleosides 8 and 10, that of 4 resulted in ring-opening to produce 9. Attempted enzymic glycosylation of 2a with purine nucleoside phosphorylase failed to yield any nucleoside product.

The Synthesis, Structure, and Conformation of 2′-Deoxy Analogues of „Fat“ Xanthine Nucleosides, Containing the Imidazo[4,5-e][1,4]Diazepine Ring System

Abstract The syntheses of 1-(2-deoxy-β-D-erythro-pentofuranosyl)-4,5,7,8-tetrahydro-6H-imidazo[4,5-e] [1,4]diazepine-5,8-dione (9β), its 3-glycosyl regioisomer (16β), and their respective α anomers (9α and 16α), are reported. Conformational and configurational studies, employing 1H NMR NOE and CD spectroscopy, are described. The single-crystal X-ray structural analysis of 9β is presented. The attempted enzymic glycosylation of the heterocyclic base 6 with a bacterial purine nucleoside phosphorylase was not successful.

The Synthesis of Two Novel Ring-Expanded Xanthine Nucleosides Containing the Imidazo[4,5-e][1,4]Diazepine Ring System

Abstract The synthesis of two regioisomeric nucleosides, 4,5,7,8-tetrahydro-6H-3-(β-D-ribofuranosyl)imidazo[4,5-e][1,4]diazepin-5,8-dione (2) and its 1-glycosyl analogue (3) is reported. They were prepared by ribosydation of the heterocyclic aglycon 4 which in turn was synthesized in three steps from 4(5)-nitroimidazole-5(4)-carboxylic acid (5). Distinction between the two isomers was achieved by an unequivocal synthesis of 2.

Synthetic, Structural, and Conformational Studies of Methylated Ring-Expanded Nucleosides Containing the Ihidazo[4, 5-e][1, 4]Diazepine Ring System

Abstract Syntheses of 4- and 7-methyl 4, 5, 7, 8-tetrahydro-6H-3-(β-ribofuranosyl)imidazo[4, 5-e] [1, 4]diazepine-5, 8-dione, 3 and 1, respectively, are reported. Single-crystal X-ray diffraction analysis of the aglycon of 3 aided in confirming the site of methylation in 3, and that of 4 in elucidating the solid state conformation of 4. Solution conformations of 3 and 4, along with their parent nucleoside 1 and the latters 1-glycosyl regioisomer 2, were investigated by NOE and CD measurements.

Novel inhibitors of guanase

Abstract Synthesis and guanase inhibitory activity of two novel 5:7-fused heterocycles, 15 and 16 , containing the imidazo[4,5- e ][1,4]diazepine ring system, have been reported.

Inhibition of 5-α-Reductase (TYPE-II) Expression by Antisense 3′-Deoxy-(2′-5′) Oligonucleotide Chimeras

Abstract ABSTRACT: 3′-Deoxy-(2′-5′) oligonucleotides bind selectively to complementary RNA but not to DNA. 3′-Deoxy-(2′-5′) phosphorothioate ODN chimeras embedded with a short stretch of 3′-5′ phosphorothioate cassette are potent inhibitors of steroid 5-α-reductasc expression with significantly less non-specific interactions in cell culture.

A Unique Diaminomalonate Derivatve useful for Building Novel Heterocycles

Abstract The synthetic utility of a unique diaminomalonate derivative (1) for constructing novel heterocycles, e.g. 5, has been demonstrated.

Ring closure of diethyl 2-methoxy-2-[N-(5-amino-1-benzylimidazolyl-4-carbonyl)amino]malonate: Product structures and pathways of product formation

Ring closure of the title compound (1) with sodium methoxide in methanol yielded three products, one 5∶6-fused and two 5∶7-fused heterocyclic systems: 9-benzyl-2-methoxycarbonylhypoxanthine (2), 3-benzyl-4,5,7,8-tetrahydro-6-methoxy-6-methoxycarbonyl-6H-imidazo[4,5-e][1,4]-diazepine-5,8-dione (3), and 3-benzyl-4,5,7,8-tetrahydro-6-methoxy-6H-imidazo[4,5-e][1,4]-diazepine-5,8-dione (4). Structures and pathways of formation of all three products have been described. Structures of2 and3 were confirmed by single-crystal X-ray diffraction analyses.