Aihong Kim

Synthesis and anti-HCMV activity of novel cyclopropyl phosphonic acid nucleosides.

A simple synthetic route for novel acyclic phosphonate nucleosides is described. The characteristic cyclopropyl moiety 8 was constructed employing the Simmons-Smith reaction as key step starting from simple acyclic 2-butene-1,4-diol. The condensation of the mesylate 11 with natural nucleosidic bases (A,C,T,U) under nucleophilic substitution conditions (K2CO3, 18-Crown-6, DMF) and hydrolysis afforded the target nucleosides 16, 17, 18, and 19. In addition, the antiviral evaluations against various viruses were performed.

Simple synthesis and anti-HIV activity of novel cyclopentene phosphonate nucleosides.

A very simple synthetic route for novel cyclopentene phosphonate nucleosides is described. The characteristic cyclopentene moiety 6 was constructed via a ring-closing metathesis of divinyl 5 , which could be readily prepared from diethylmalonate. The condensation of the mesylate 11 with nucleobases (A,C,T,U) under nucleophilic substitution conditions (K 2 CO 3 , 18-Crown-6, DMF) afforded the target nucleosides 12 , 13 , 14 , and 15 . In addition, the antiviral evaluations against various viruses were performed.

Synthesis and anti-HIV Study of Novel Acyclic Guanine Derivatives

This paper reports a new method for synthesizing an acyclic version of 6 ′-methylene and 6 ′(α)-methylated carbovir analogues. The introduction of a methylene group to the requisite 6 ′-position was carried out employing a Mannich type reaction using Eshenmosers salt (methylene-N,N-dimethylammonium iodide). Carbonyl enolate alkylation (LiHMDS, CH3I) was used to introduce a methyl group to the 6 ′(α)-position. The guanine analogues were successfully synthesized from the bromide compound 8 and 14 via a SN2 type reaction and deprotection. When the synthesized compounds 11 and 17 were tested against HIV-1, they showed toxicity that was not related to any anti-HIV activity.

Racemic Synthesis and Antiviral Evaluation of 4′(α)-Hydroxymethyl and 6′(α)-Methyl Substituted Apiosyl Nucleosides

This article reports the novel synthesis of substituted apiosyl nucleosides. The key apiosyl intermediate 9 was constructed by sequential ozonolysis, reductions, and acetylation from the ester derivative 6. The nucleosides of uracil, thymine, cytosine, and adenine were synthesized using the glycosyl condensation procedure (silyated base and TMSOTf). The antiviral activities of the synthesized compounds against the HIV-1, HSV-1, HSV-2, and HCMV viruses were evaluated. The adenine derivative 26 showed weak anti-HIV activity (EC50 = 10.1 μg/ml) without exhibiting any cytotoxicity up to a concentration of 100 μM.

Synthesis and antiviral evaluation of novel 5'-norcarboacyclic phosphonic acid nucleosides.

This article describes a very simple route for synthesizing a novel 5′-norcarboacyclic nucleotides. The condensation of the mesylates 17 and 18 with the natural nucleosidic bases (A,U,T,C) under standard nucleophilic substitution (K2CO3, 18-Crown-6, DMF) and deprotection afforded the target nucleotide analogues 27–34. In addition, these compounds were evaluated for their antiviral properties against various viruses.

Synthesis and Anti-HCMV Activity of Novel 2′,3′,4′-Trimethyl Branched Carbocyclic Nucleosides

This article reports the synthesis of novel 2′,3′,4′-trimethyl branched carbocyclic nucleosides. The introduction of a methyl group in the 2′ and 3′-position was accomplished by sequential Horner–Wadsworth–Emmons reaction and isopropenyl magnesiumbromide addition, respectively. The construction of the 4′-quaternary carbon needed was carried out using a [3,3]-sigmatropic rearrangement. Bis -vinyls were successfully cyclized using a Grubbs’ catalyst II. The natural bases (adenine, cytosine) were efficiently coupled with the use of a Pd(0) catalyst.

Synthesis and antiviral activity of novel 2',4'-doubly branched carbocyclic nucleosides.

A series of 2′ and 4′‐doubly branched carbocyclic nucleosides 15, 16, 17 and 18 were synthesized starting from simple acyclic ketone derivatives. The required 4′‐quaternary carbon was constructed using Claisen rearrangement. In addition, the installation of a methyl group in the 2′‐position was accomplished using a Grignard carbonyl addition of isopropenylmagnesium bromide. Bis‐vinyl was successfully cyclized using a Grubbs’ catalyst II. Natural bases (adenine, cytosine) were efficiently coupled by using Pd(0) catalyst.

Synthesis and antiviral activity of novel anomeric branched carbocyclic nucleosides

Novel anomeric branched carbocyclic nucleosides were synthesized from 1,3-dihydroxy acetone. 4′-Hydroxymethyl was installed by [3,3]-sigmatropic rearrangement reaction and 1′-methyl group was introduced by carbonyl addition of methylmagnesium bromide. The coupling of nucleosidic bases and desilylation afforded a series of novel nucleosides. The synthesized compounds16–19 were evaluated for their antiviral activity against HIV-1, HSV-1, HSV-2, and EMCV. Compounds16 and19 exhibit toxicity non-related to any anti-HIV-1 activity.