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Ribavirin is an unnatural nucleoside exhibiting broad spectrum of antiviral and antitumor activities, still very widely studied particularly in a repositioning approach. C-triazolyl nucleoside analogues of ribavirin have been synthesized, as well as prodrugs and glycosylated or peptide conjugates to allow a better activity by vectorization into the liver or by facilitating uptake into the cells. The antiviral properties of all synthesized compounds have been evaluated in vitro against two important human viral pathogens belonging to the Flaviviridae family: hepatitis C virus (HCV) and Zika virus (ZIKV). There are no therapeutic options for Zika virus, whereas those available for HCV can be still improved. Our results indicated that compound 2 carrying an N-hydroxy carboxamide function exhibits the most inhibitory activities against both viruses. This compound moderately inhibited the propagation of HCV with an IC

Because of the emergence of new viruses, the need for new antiviral broad-spectrum compounds remains important. In this context, herein the synthesis of C-nucleosides, structurally close to ribavirin, a nucleoside presenting various biological activities and used until now particularly for its broad-spectrum antiviral properties, is reported. The compounds were designed in order to increase their stability and the number of hydrogen bond donor or acceptor in comparison to ribavirin, and to investigate the role of the carboxamide group on the biological activity. The efficient synthesis of 11 C-nucleosides is based on an indium-mediated alkynylglycosylation as the key step, followed by the construction of the triazole heterocycle. Amidation was performed with primary and secondary amines in yields up to 85%. An analogue nucleoside with a triazole without carboxamide group was also prepared in order to compare its activity. Finally, the carboxamide group was moved to the N-1 triazole position to mimic ribavirin.

This study reports the high enantiomeric preference of whole cell lipase from Aspergillus flavus wild-type that allows the preparation of a chiral secondary alcohol. Whole cells prepared from a wild-type Aspergillus flavus strain were used as biocatalysts to prepare (R)-1-phenylethyl acetate. (R)-1-Phenylethanol was esterified into (R)-1-phenylethyl acetate with a 94.6% enantiomeric excess (ee) within 24 h at 40 °C and (S)-1-phenylethanol remained in the reaction medium with a >99%ee. Besides, this biocatalyst allows the preparation of ethyl laurate and a mixture of 2-chloro-1-(chloromethyl)ethyl acrylate and 2,3-dichloro-1-propyl acrylate. The ethyl laurate yield was 96%, whereas the synthesis of a mixture of the acrylate regioisomers, 2-chloro-1-(chloromethyl)ethyl acrylate and 2,3-dichloro-1-propyl acrylate gave similar yields to those obtained using commercial lipases.

The anticipated worldwide increase in biodiesel production will result in an accumulation of glycerol for which there are insufficient conventional uses. The surplus of this by-product has increased rapidly during the last decade, prompting a search for new glycerol applications. We describe here the synthesis of dissymmetric chlorohydrin esters from symmetric 1,3-dichloro-2-propyl esters obtained from glycerol. We studied the influence of two solvents: 1,4-dioxane and 1-butanol and two bases: sodium carbonate and 1-butylimidazole, on the synthesis of dissymmetric chlorohydrin esters. In addition, we studied the influence of other bases (potassium and lithium carbonates) in the reaction using 1,4-dioxane as the solvent. The highest yield was obtained using 1,4-dioxane and sodium carbonate. This work was supported by a Grant-in-Aid from the Secretaría de Estado de Política Cientifíca y Tecnológica of the Spanish Ministry of Education and Culture (contract Grant No.: CTQ2009-14699- C02-01). The authors are grateful to the Comissionat per a Universitats i Recerca del Departament d’Innovació, Universitats i Empresa de la Generalitat de Catalunya and to the European social Fund (EFS) for the FI grant of Carmen Solarte Orozco.

Following our preparation of dissymmetric chlorohydrin esters from glycerol, we have used several lipases and whole cells to examine the kinetic resolution (KR) and dynamic kinetic resolution (DKR) of 3-chloro-2-hydroxypropyl esters. Regarding the KR, PS-IM, MmL and CALB lipases and whole cells of Aspergillus flavus showed the best selectivity and activity, depending on the compound studied. PS-IM allowed the isolation of (R)-3-chloro-2-hydroxypropyl pivaloate in 34% yield and with >99% enantiomeric excess (ee). DKR was carried out combining the biocatalysts that performed best for KR and suitable reaction conditions for racemization. Whole cells of A. flavus allowed the preparation of enantioenriched (S)-3-chloro-2-acetoxypropyl-2-methyl-2-phenyl propanoate in 43% yield and with 79% ee. Lipozyme from Mucor miehei used in a reaction subsequent to DKR allowed the purification of the corresponding enantioenriched (S)-3-chloro-2-acetoxypropyl pivaloate.