Elena N. Kalinichenko

Synthesis of 2-Chloro-2′-Deoxyadenosine by Microbiological Transglycosylation

Abstract The title compound have been synthesized by an enzymatic trans-2′-deoxyribosylation of 2-chloroadenine using the whole cells of E. coli BMT-1D/1A as a biocatalyst and 2′-deoxyguanosine as a donor of glycosyl moiety.

1-Deaza and 3-deazapurines in the reaction of microbiological transglycosylation

SummarySubstrate activity of 1- and 3-deazapurines in the reaction of microbiological ribo- 2-deoxyribosylation catalysed by purine nucleoside phosphorylase of viable cells ofE. coli BMT-1D/1A has been studied. Guanosine or 2′-deoxyguanosine were used as donors. 1-Deazapurines are good substrates in both reactions; 3-deazapurines are very effective intransdeoxyribosylation but not intransribosylation. Benzimidazole is an excellent substrate in both reactions indicating that N(1) and N(3) are not essential for transglycosylation.

Microbiological synthesis of 5-ethyl- and (E)-5-(2-bromovinyl)-2′-deoxyuridine

SummaryThe title compounds were prepared by an enzymatic transdeoxyribosylation from 2′ dGuo or 2′ dThd to the respective heterocyclic bases, 5-ethyluracil and (E)-5-(2-bromovinyl)uracil, using the whole bacterial cells ofEscherichia coli as a biocatalyst.

Synthesis of 1-Deazaadenosine Analogues of (2′→5′) ApApA

Abstract Synthesis of (2′ → 5′)ApApA analogues containing 1-deazaadenosine at different positions is described (32–34). The approach used the phosphotrieer methodology in solution and utilized 3′-O-benzoylated derivatives of the N6-protected 5′-O-monomethoxytrityl-1-deazaadenosine as starting material. Dedicated to Prof. Y. Mizuno on the occasion of his 75th birthday

Synthesis and antiviral activity of purine 2',3'-dideoxy-2',3'-difluoro-D-arabinofuranosyl nucleosides.

9-(2′,3′-Dideoxy-2′,3′-difluoro-β-D-arabinofuranosyl)adenine (20), 2-chloro-9-(2′,3′-dideoxy-2,3-difluoro-β-D-arabinofuranosyl)adenine (22), as well as their respective α-anomers 21 and 23, were synthesized by the nucleobase anion glycosylation of intermediate 5-O-benzoyl-2,3-dideoxy-2,3-difluoro-α-D-arabinofuranosyl bromide (13) starting from methyl 5-O-benzyl-3-deoxy-3-fluoro-α-D-ribofuranoside (3) and methyl 5-O-benzoyl-α-D-xylofuranoside (10). These compounds were evaluated as potential inhibitors of HIV-1 and hepatitis C virus in human PBM and Huh-7 Replicon cells, respectively. The adenosine analog 20 demonstrated potent activity against HIV-1 in primary human lymphocytes with no apparent cytotoxicity. Conformation of pentofuranose ring of nucleoside 20 in solution was studied by PSEUROT calculations.

A comparison of enzymatic phosphorylation and phosphatidylation of β- l - and β- d -nucleosides

Enzymatic 5′-monophosphorylation and 5′-phosphatidylation of a number of β-l- and β-d-nucleosides was investigated. The first reaction, catalyzed by nucleoside phosphotransferase (NPT) from Erwinia herbicola, consisted of the transfer of the phosphate residue from p-nitrophenylphosphate (p-NPP) to the 5′-hydroxyl group of nucleoside; the second was the phospholipase d (PLD)-catalyzed transphosphatidylation of l-α-lecithin with a series of β-l- and β-d-nucleosides as the phosphatidyl acceptor resulted in the formation of the respective phospholipid-nucleoside conjugates. Some β-l-nucleosides displayed similar or even higher substrate activity compared to the β-d-enantiomers.

Ability of adenosine-2'(3')-deoxy-3'(2')-triphosphates and related analogues to replace ATP as phosphate donor for all human and Drosphila melanogaster deoxyribonucleoside kinases.

Abstract Six non-conventional adenosine-2′- and 3′-triphosphate analogues of ATP were tested as potential phosphate donors for all four human, and D. melanogaster, deoxyribonucleoside kinases. With dCK (only dAdo as acceptor), TK1, TK2 and dNK only 3′-deoxyadenosine-2′-triphosphate was an effective donor (5–60% that for ATP). With dCK (dCyd as acceptor) and dGK (dGuo as acceptor), sharing 45% sequence identity, donor activities ranged from 13 to 119% that for ATP. Products were 5′-phosphates. In some instances, kinetics are dependent on the nature of the acceptor, and donor and acceptors properties are mutually interdependent. Results are highly relevant to studies on the modes of interaction with the enzymes, and to interpretations of reported crystal structures of dCK and dNK with bound ligands.

Stereospecific Synthesis and Anti-HIV Activity of (Z)2′- and (E)3′-Deoxy-2′(3′)-C-(chloromethylene) Pyrimidine Nucleosides

Abstract Reaction of 1-[2,5(and 3,5)-di-O-trityl-β-D-erythro-pentofuran-3 (and 2)-ulosyl]uracil derivatives 5 and 6 with (chloromethyl)triphenylphosphorane resulted in the stereoselective formation of (E)-3′- and (Z)-2′-chloromethylene derivatives 7 (69%) and 8 (53%), respectively, deprotection of which gave 9 and 10. Transformation of the uracil nucleoside 7 into cytosine one followed by deprotection yielded 12. The latter was converted into the arabinoside 14. The fully deprotected chloromethylene nucleosides were tested for their activity against HIV-1 and HIV-2.

Synthesis of 9-(2,3-Dideoxy-2,3-Difluoro-β-D- Arabinofuranosyl)Adenine

Convergent synthesis of 9-(2,3-dideoxy-2,3-difluoro-β-D-arabinofuranosyl)adenine is described starting from methyl 5-O-benzyl-2-deoxy-2-fluoro-α-D-arabinofuranoside.

A 2′←5′-Adenylate Trimer With a Positively Charged 2′(3′)-Terminal 8-(4-Aminobunl)Aminoadenosine Residue: Synthesis, Conformation and RNase L Binding

Abstract An analogue of the 2-5A core trimer containing an 8-(4-aminobutyl)-aminoadenosine (1; A) residue at the 2′(3′)-terminus [2; (2′,5′)A2A∗] was synthesized. The conformation of (2′,5′)A2A∗ was studied by 1H, 13C-NMR, and CD spectroscopy. The (2′,5′)A2A∗ exhibits very low binding ability to the RNase L of mouse L cells, but slightly enhanced resistance to digestion by SVPD compared to the parent trimer.