Chemoenzymatic Synthesis of Novel 3‘- and 5‘-Carbazoyl Nucleoside Derivatives. Regioselective Preparation of 3‘- and 5‘-Alkylidencarbazoyl Nucleosides

Abstract

A chemoenzymatic procedure is described for the synthesis of 3‘- and 5‘-carbazoyl nucleoside derivatives 12a,b, 13a,b, 14b,c, and 30b, and these are prepared for the first time. This process involves the regioselective enzymatic alkoxycarbonylation of nucleosides and the subsequent transformation with hydrazine into novel carbazoyl nucleoside derivatives. Taking into account previously reported data (relative to nucleoside, hydrazone, carbazate, and aryloxyphenoxypropionate derivatives), 3‘-alkylidencarbazoyl 2‘-deoxynucleosides 15a,b−18a,b, 5‘-alkylidencarbazoyl 2‘-deoxynucleosides 19a,b−22a,b, 5‘-alkylidencarbazoyl ribonucleosides of uridine 23c−26c, and 5‘-alkylidencarbazoyl-2‘,3‘-isopropylideneadenosine 31b−34b emerge as interesting targets since they combine structural features found in both therapeutic nucleoside derivatives and fungicide/herbicide nucleoside analogues.

Biocatalytic Selective Modifications of Conventional Nucleosides, Carbocyclic Nucleosides, and C-Nucleosides

“…A chemoenzymatic procedure for the synthesis of 3‘- and 5‘-carbazoyl nucleoside derivatives prepared for the first time is shown in Scheme . This process involves the regioselective enzymatic alkoxycarbonylation of nucleosides 86 and the subsequent transformation with hydrazine into novel carbazoyl nucleoside derivatives 87 or 88 .…”

“…A chemoenzymatic procedure for the synthesis of 3′-and 5′-carbazoyl nucleoside derivatives prepared for the first time is shown in Scheme 23. 38 This process involves the regioselective enzymatic alkoxycarbonylation of nucleosides 86 and the subsequent transformation with hydrazine into novel carbazoyl nucleoside derivatives 87 or 88. Taking into account previously reported data (relative to nucleoside, hydrazone, carbazate, and aryloxyphenoxypropionate derivatives), 3′-alkylidencarbazoyl 2′-deoxynucleosides (90), 5′-alkylidencarbazoyl 2′-deoxynucleosides, and 5′-alkylidencarbazoyl ribonucleosides (89), emerge as interesting targets, since they combine structural features found in both therapeutic nucleoside derivatives and fungicide/herbicide nucleoside analogues.…”

Synthesis of some novel hydrazono acyclic nucleoside analogues

“…Acyclic nucleosides constitute a special class of nucleoside analogues which have attracted great interest due to their broad-spectrum chemotherapeutic activities against cancer and infections caused by viruses, microbes and other pathogenic microorganisms. Moreover, antitumor and antiviral activities of various hydrazone derivatives of nucleosides have also been reported [ 16 – 18 ].…”

Biocatalysis Applied to the Synthesis of Agrochemicals

“…Thus, nucleoside derivatives have been used as antitumoral and antiviral agents, notably against the human immunodeficiency virus [13,14,15]. Gotor et al [16] described a chemoenzymatic procedure for the synthesis of novel nucleoside derivatives that combines the structural features found in both therapeutic nucleoside derivatives and their analogous herbicide nucleosides. The chemoenzymatic process involves the regioselective enzymatic alkoxycarbonylation of nucleosides with acetone O-[(vinyloxy) carbonyl]oxime (VCO) as the alkoxy-carbonylating reagent at 30ºC in tetrahydrofurane (THF) with Candida antarctica lipase (CAL) as the biocatalyst, (Fig.…”