Ring Transformations of Pentose Glycals with Push-Pull Butadiene Functionality

Abstract

2-Formyl-D-xylal (1a) and 2-formyl-L-arabinal (1b) were reacted with alkyl cyanoacetates to furnish the 1,5-anhydro-3,4-di-O-benzyl-2-[(E)-2-cyano-2-alkoxycarbonylvinyl]-2-deoxy-D(L)-hex-1-enitols 2a and 2b, respectively. Treatment of 2a, 2b with aromatic amines afforded the 1-aryl-5-[1,2-bis(benzyloxy)-3-hydroxypropyl]-1,2-dihydro-2-oxopyridine-3-carbonitriles 3a-c. Ring transformation of 1a, 1b with N-substituted oxobutyramides, dialkyl 3-oxopentanedioate and benzimidazol-2-ylacetonitrile yielded the 3-acetyl-1-aryl-5-[1,2-bis(benzyloxy)-3-hydroxypropyl]-1,2-dihydropyridin-2-ones 6a-d, alkyl 5-[1,2-bis(benzyloxy)-3-hydroxypropyl]-2-hydroxyisophthalates 8a-d and 2-[1,2-bis(benzyloxy)-3-hydroxypropyl]benzo [4,5]imidazo-[1,2-a]-pyridine-4-carbonitriles 11a, 11b, respectively.Analogues of nucleosides in which an open-chain monosaccharide unit is linked via a C-C single bond to the heterocyclic part have received considerable attention in recent years due to their diverse biological properties. [1][2][3][4][5] We have previously reported the ring transformation reactions of 2-formyl glycals in the hexose series. 6-12 Recently, the first reactions of pentose glycals with nitrogen nucleophiles to yield acyclo-C-nucleoside analogues were described. 13 The double bond of these branched chain enesugars was push-pull activated and, therefore, susceptible to nucleophilic attack by different N-nucleophiles. Herein, we report the syntheses of C-2 branched-chain pentose glycals with an integrated push-pull butadiene unit that after reacting with different nucleophiles should give different acyclo-C-nucleoside analogues and acyclo-Cglycosides, respectively. Treatment of 1,5-anhydro-3,4-di-O-benzyl-2-deoxy-2-formyl-D-threo-hex-1-enitol (1a) 13 with ethyl cyanoacetate and 1,5-anhydro-3,4-di-O-benzyl-2-deoxy-2-formyl-L-erythro-hex-1-enitol (1b) 13 with methyl cyanoacetate under Knoevenagel conditions gave the monosaccharide push-pull butadienes 2a and 2b, respectively, in moderate to high yields (Scheme 1). The reactions were performed by using piperidinium acetate as the most efficient cataScheme 1 Reagents and conditions: (i) piperidine, AcOH, toluene, reflux (ii) EtOH, reflux; (iii) piperidine, AcOH, chlorobenzene, refluxR 2 R 1 O BnO O NHR 4 NC N R 4 CN O HO OBn R 2 R 1 2 a : R 1 = H, R 2 = BnO, R 3 = Et (92%) 2 b : R 1 = BnO, R 2 = H, R 3 = Me (56%) R 2 R 1 O BnO 3 a : R 1 = H, R 2 = BnO, R 4 = p-MeOC 6 H 4 (2a, ii: 62%; 1 a , iii: 95%) 3 b : R 1 = BnO, R 2 = H, R 4 = Ph (2b, ii: 41%) 3 c : R 1 = BnO, R 2 = H, R 4 = p-MeOC 6 H 4 (2b, ii: 65%; 1 b , iii: 63%) 3 d : R 1 = BnO, R 2 = H, R 4 = H (1b, iii: 57%) COOR 3 NC (ii) 1 a , 1 b (iii) R 3 = Me R 3 = Et R 4 = Ph R 4 = p-MeOC 6 H 4

Synthesis, Antiviral, and Antimicrobial Evaluation of Benzyl Protected Diversified C-nucleosides

“…Presumably, the reaction proceed by the nucleophilic attack of hydrazine which acts as dinucleophiles at C-1 which resulted in the ring opening of glycals followed by the cyclization involving formyl group (Scheme 3). The products were confirmed by 1 H and 13 C NMR spectroscopy in which the spectra of these compounds showed the absence of signals for formyl group instead the typical long range coupling of pyrazole protons were observed confirming the successful ring transformation (Montero et al, 2004; Bari et al, 2005b). The products were purified by column chromatography and were obtained in quantitative yield with no side products formed.…”