51d977a9899787c7d63ac48ba2ce49f0 IntJouMolSci_a2022v23n17p9704iENG.pdf 643f8f83020b3e011d60aa0f3214210ae3b5db54 IntJouMolSci_a2022v23n17p9704iENG.pdf 114b5bc2765c0c0db1fca18ea8824eeeac71122b8e6a80668bdedae4108053d7 IntJouMolSci_a2022v23n17p9704iENG.pdf Title: Enantiocontrolled Preparation of -Substituted Cyclohexenones: Synthesis and Kinase Activity Assays of Cyclopropyl-Fused Cyclohexane Nucleosides Subject: The enantioselective preparation of the two isomers of 4-hydroxy-2-cyclohexanone derivatives 1a,b was achieved, starting from a common cyclohexenone, through asymmetric transfer hydrogenation (ATH) reactions using bifunctional ruthenium catalysts. From these versatile intermediates, a stereoselective route to a cytosine analogue built on a bicyclo [4.1.0]heptane scaffold is described. Nucleoside kinase activity assays with this cyclopropyl-fused cyclohexane nucleoside, together with other related nucleosides (2a–e), were performed, showing that thymine- and guanine- containing compounds have affinity for herpes simplex virus Type 1 (HSV-1) thymidine kinase (TK) but not for human cytosolic TK-1, thus pointing to their selectivity for herpetic TKs but not cellular TKs. Keywords: asymmetric synthesis; carbocyclic nucleosides; HSV-1 thymidine kinase; enzymatic assays Author: Sergio Jurado, Beatriz Domínguez-Pérez, Ona Illa, Jan Balzarini, Félix Busqué and Ramon Alibés Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Aug 29 03:49:13 2022 CEST ModDate: Mon Aug 29 04:01:16 2022 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1696823 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- YSPQJI+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 CIQLLF+VnURWPalladioL Type 1 Custom yes yes no 15 0 AGQKCM+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 TDNESP+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 QMQJLY+PazoMath Type 1 Builtin yes yes no 28 0 JVZAUB+URWPalladioL-Ital Type 1 Custom yes yes no 32 0 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Domínguez-Pérez, Ona Illa, Jan Balzarini, Félix Busqué and Ramon Alibés Subject: The enantioselective preparation of the two isomers of 4-hydroxy-2-cyclohexanone derivatives 1a,b was achieved, starting from a common cyclohexenone, through asymmetric transfer hydrogenation (ATH) reactions using bifunctional ruthenium catalysts. From these versatile intermediates, a stereoselective route to a cytosine analogue built on a bicyclo [4.1.0]heptane scaffold is described. Nucleoside kinase activity assays with this cyclopropyl-fused cyclohexane nucleoside, together with other related nucleosides (2a e), were performed, showing that thymine- and guanine- containing compounds have affinity for herpes simplex virus Type 1 (HSV-1) thymidine kinase (TK) but not for human cytosolic TK-1, thus pointing to their selectivity for herpetic TKs but not cellular TKs. 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