First Synthesis and Anti-HIV Evaluation of 4′-Methyl-Cyclopentanyl 9-Deazaadenosine

Abstract

The first synthesis of a 4'-methylated carbocyclic C-nucleoside 16 was achieved via the mesylate intermediate 10, which was prepared using ring-closing metathesis and S(N)2 alkylation from acetol 5. When antiviral evaluation of synthesized compound 16 was performed against various viruses such as HIV, HSV-1, HSV-2, and HCMV, it showed moderate anti-HIV activity in MT-4 cell line (EC(50) = 14.7 micromol).

Nucleosides with Transposed Base or 4′-Hydroxymethyl Moieties and Their Corresponding Oligonucleotides

“…Lewis acid-catalyzed glycosylation of acetylated lactols 225 and 227 with persilylated nucleobases led to the formation of the corresponding 3′-hydroxymethyl and 3′-vinyl branched apionucleosides, respectively. Besides, similar chemical transformations enabled the preparation of 3′-phenyl, 2′-methyl-3′-(hydroxymethyl) ( 42 and 43 ), and 4′-methyl-3′-(hydroxymethyl) ( 44 and 45 ) branched-chain analogues, as well as 3′-(hydroxymethyl)-4′-thioapiosyl isosteres 41 , l -apio-C-nucleosides 129 and 130 , and carbocyclic products 131 and 132 . , …”

“…Both analogues exhibit moderate to poor activity against HSV-1, HSV-2, and HCMV (EC 50 = 97.2–209 μM). Compounds 131 and 132 show moderate activity against HIV-1 (EC 50 = 25.1 and 14.7 μM, respectively) in MT-4 cells, without any cytotoxicity up to a concentration of 100 μM. , Kim et al synthesized the ribavirin-type apionucleoside 133 and its thiazole analogue 134 . Both compounds were devoid of notable activity against a panel of viruses.…”

A review of methods to synthesise 4′-substituted nucleosides

“…The Grubbs catalyst based approach has also been used to access a range of 4′-substituted 2′,3′-dideoxy carbocyclic nucleosides, a selection of which is detailed in Scheme 29. [53][54][55]…”