Synthesis of Ribavirin, Tecadenoson, and Cladribine by Enzymatic Transglycosylation

Despite the impressive progress in nucleoside chemistry to date, the synthesis of nucleoside analogues is still a challenge. Chemoenzymatic synthesis has been proven to overcome most of the constraints of conventional nucleoside chemistry. A purine nucleoside phosphorylase from <i>Aeromonas hy...

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Main Authors:	Marco Rabuffetti, Teodora Bavaro, Riccardo Semproli, Giulia Cattaneo, Michela Massone, Carlo F. Morelli, Giovanna Speranza, Daniela Ubiali
Format:	Article
Language:	English
Published:	MDPI AG 2019-04-01
Series:	Catalysts
Subjects:	Ribavirin Tecadenoson Cladribine purine nucleoside phosphorylase transglycosylation reaction 7-methylguanosine iodide 7-methyl-2′-deoxyguanosine iodide 7-methylguanine arabinoside iodide
Online Access:	https://www.mdpi.com/2073-4344/9/4/355

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spelling	doaj-5a7096f3f360488d832863459766e0662020-11-25T02:18:08ZengMDPI AGCatalysts2073-43442019-04-019435510.3390/catal9040355catal9040355Synthesis of Ribavirin, Tecadenoson, and Cladribine by Enzymatic TransglycosylationMarco Rabuffetti0Teodora Bavaro1Riccardo Semproli2Giulia Cattaneo3Michela Massone4Carlo F. Morelli5Giovanna Speranza6Daniela Ubiali7Department of Chemistry, University of Milan, via Golgi 19, I-20133 Milano, ItalyDepartment of Drug Sciences, University of Pavia, viale Taramelli 12, I-27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, viale Taramelli 12, I-27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, viale Taramelli 12, I-27100 Pavia, ItalyDepartment of Chemistry, University of Milan, via Golgi 19, I-20133 Milano, ItalyDepartment of Chemistry, University of Milan, via Golgi 19, I-20133 Milano, ItalyDepartment of Chemistry, University of Milan, via Golgi 19, I-20133 Milano, ItalyDepartment of Drug Sciences, University of Pavia, viale Taramelli 12, I-27100 Pavia, ItalyDespite the impressive progress in nucleoside chemistry to date, the synthesis of nucleoside analogues is still a challenge. Chemoenzymatic synthesis has been proven to overcome most of the constraints of conventional nucleoside chemistry. A purine nucleoside phosphorylase from <i>Aeromonas hydrophila</i> (<i>Ah</i>PNP) has been used herein to catalyze the synthesis of Ribavirin, Tecadenoson, and Cladribine, by a “one-pot, one-enzyme„ transglycosylation, which is the transfer of the carbohydrate moiety from a nucleoside donor to a heterocyclic base. As the sugar donor, 7-methylguanosine iodide and its 2′-deoxy counterpart were synthesized and incubated either with the “purine-like„ base or the modified purine of the three selected APIs. Good conversions (49–67%) were achieved in all cases under screening conditions. Following this synthetic scheme, 7-methylguanine arabinoside iodide was also prepared with the purpose to synthesize the antiviral Vidarabine by a novel approach. However, in this case, neither the phosphorolysis of the sugar donor, nor the transglycosylation reaction were observed. This study was enlarged to two other ribonucleosides structurally related to Ribavirin and Tecadenoson, namely, Acadesine, or AICAR, and 2-chloro-<i>N</i><sup>6</sup>-cyclopentyladenosine, or CCPA. Only the formation of CCPA was observed (52%). This study paves the way for the development of a new synthesis of the target APIs at a preparative scale. Furthermore, the screening herein reported contributes to the collection of new data about the specific substrate requirements of <i>Ah</i>PNP.https://www.mdpi.com/2073-4344/9/4/355RibavirinTecadenosonCladribinepurine nucleoside phosphorylasetransglycosylation reaction7-methylguanosine iodide7-methyl-2′-deoxyguanosine iodide7-methylguanine arabinoside iodide
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Marco Rabuffetti Teodora Bavaro Riccardo Semproli Giulia Cattaneo Michela Massone Carlo F. Morelli Giovanna Speranza Daniela Ubiali
spellingShingle	Marco Rabuffetti Teodora Bavaro Riccardo Semproli Giulia Cattaneo Michela Massone Carlo F. Morelli Giovanna Speranza Daniela Ubiali Synthesis of Ribavirin, Tecadenoson, and Cladribine by Enzymatic Transglycosylation Catalysts Ribavirin Tecadenoson Cladribine purine nucleoside phosphorylase transglycosylation reaction 7-methylguanosine iodide 7-methyl-2′-deoxyguanosine iodide 7-methylguanine arabinoside iodide
author_facet	Marco Rabuffetti Teodora Bavaro Riccardo Semproli Giulia Cattaneo Michela Massone Carlo F. Morelli Giovanna Speranza Daniela Ubiali
author_sort	Marco Rabuffetti
title	Synthesis of Ribavirin, Tecadenoson, and Cladribine by Enzymatic Transglycosylation
title_short	Synthesis of Ribavirin, Tecadenoson, and Cladribine by Enzymatic Transglycosylation
title_full	Synthesis of Ribavirin, Tecadenoson, and Cladribine by Enzymatic Transglycosylation
title_fullStr	Synthesis of Ribavirin, Tecadenoson, and Cladribine by Enzymatic Transglycosylation
title_full_unstemmed	Synthesis of Ribavirin, Tecadenoson, and Cladribine by Enzymatic Transglycosylation
title_sort	synthesis of ribavirin, tecadenoson, and cladribine by enzymatic transglycosylation
publisher	MDPI AG
series	Catalysts
issn	2073-4344
publishDate	2019-04-01
description	Despite the impressive progress in nucleoside chemistry to date, the synthesis of nucleoside analogues is still a challenge. Chemoenzymatic synthesis has been proven to overcome most of the constraints of conventional nucleoside chemistry. A purine nucleoside phosphorylase from <i>Aeromonas hydrophila</i> (<i>Ah</i>PNP) has been used herein to catalyze the synthesis of Ribavirin, Tecadenoson, and Cladribine, by a “one-pot, one-enzyme„ transglycosylation, which is the transfer of the carbohydrate moiety from a nucleoside donor to a heterocyclic base. As the sugar donor, 7-methylguanosine iodide and its 2′-deoxy counterpart were synthesized and incubated either with the “purine-like„ base or the modified purine of the three selected APIs. Good conversions (49–67%) were achieved in all cases under screening conditions. Following this synthetic scheme, 7-methylguanine arabinoside iodide was also prepared with the purpose to synthesize the antiviral Vidarabine by a novel approach. However, in this case, neither the phosphorolysis of the sugar donor, nor the transglycosylation reaction were observed. This study was enlarged to two other ribonucleosides structurally related to Ribavirin and Tecadenoson, namely, Acadesine, or AICAR, and 2-chloro-<i>N</i><sup>6</sup>-cyclopentyladenosine, or CCPA. Only the formation of CCPA was observed (52%). This study paves the way for the development of a new synthesis of the target APIs at a preparative scale. Furthermore, the screening herein reported contributes to the collection of new data about the specific substrate requirements of <i>Ah</i>PNP.
topic	Ribavirin Tecadenoson Cladribine purine nucleoside phosphorylase transglycosylation reaction 7-methylguanosine iodide 7-methyl-2′-deoxyguanosine iodide 7-methylguanine arabinoside iodide
url	https://www.mdpi.com/2073-4344/9/4/355
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Synthesis of Ribavirin, Tecadenoson, and Cladribine by Enzymatic Transglycosylation

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