The Controlled Stereospecific Reduction of Cyclopentenyl Cytosine (CPE-C) to Carbodine and Isocarbodine

Abstract

The preferential cis-addition of hydrogen to either face of the carbocyclic double bond of enantiomerically pure cyclopentenyl cytosine (1) was achieved. The resulting saturated carbocyclic nucleosides carbodine (2) and isocarbodine (3) were evaluated against human influenza virus. Carbodine showed the greater potency against this virus but the activity of isocarbodine was still substantial.     

Enantioselective Synthesis of Carbocyclic Nucleosides by Enzymatic Approach and the Anticancer Activities

Abstract

Enantioselective synthesis of carbocyclic nucleosides, aristereomycin, neplanomycin A and their homologues has been completed by a combination of enzymatic and non-enzymatic procedures starting with a bicyclic meso-diester 2. The study on anticancer activities of them showed that the cytosine homologue exhibits most remarkable activity against L1210 leukemia in mice.     

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'-quatemary 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.     

Deamination of 9-(Hydroxymethylated cycloalkyl)-9H-adenines (Carbocyclic Adenine Nucleosides) by Adenosine Deaminase: Effect of High-Pressure Upon Deamination Rate and Enantioselectivity

Abstract

The deamination of eight kinds of racemic carbocyclic adenine nucleosides by adenosine deaminase under high-pressure (400 MPa) was examined and the result was compared with that obtained from the reaction under atmospheric pressure. The deamination of all carbocyclic nucleosides irrespective to their ring size of carbocycles was facilitated remarkably high-pressure. The reaction of three and five membered carbocyclic nucleosides resulted in the very high enantioselectivity both under high- and atmospheric Plessure whereas the enantioselectivity of six membered carbocyclic nucleosides was suppressed under high-pressure. However, the enantioselectivity of four membered nucleosides was low under both conditions.

     

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(O) catalyst.     

Asymmetric Synthesis of Cyclopropyl Carbocyclic Nucleosides

Abstract

A number of nucleosides have been synthesized as potential antiviral and antitumor agents.¹ More recently, various dideoxynucleosides have been synthesized and found to be potent anti-HIV agents.² As a part of our drug discovery program for the treatment of HIV and HBV, we have initiated to synthesize cyclopropyl carbocyclic nucleosides as potential antiviral agents. Several papers regarding the synthesis of cyclopropyl carbocyclic nucleosides have appeared in the literature.^3–5 However, they are all reported as racemic mixtures. In this abstract, we wish to report the asymmetric synthesis of cylopropyl carbocyclic nucleosides from optically active common intermediates, 6 and 11.     

A facile synthesis of cis-4-amino-2-cyclopentene-1-methanol, a key intermediate for the synthesis of carbocyclic nucleosides

A number of carbocyclic nucleosides can be synthesized from (+/-)-cis-4-amino-2-cyclopentene-1-methanol (3). Carbocyclic amino alcohol 3 is a key intermediate that makes possible the efficient synthesis of the carbocyclic nucleosides. In this study we wish to report an efficient synthesis of carbocyclic amino alcohol 3 from inexpensive and readily available starting material. The synthetic route employed cyclopentadiene (4) as a starting material and proceeded in 38% overall yield through 6 steps involving a hetero Diels-Alder reaction and an aza-Claisen rearrangement.     

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 OF CARBOCYCLIC ANALOGS OF 2′,3′-DIDEOXYSANGIVAMYCIN, 2′,3′-DIDEOXYTOYOCAMYCIN,AND 2′,3′-DIDEOXYTRICIRIBINE

Syntheses and antiviral activity of new carbocyclic analogs of 2′, 3′-dideoxysangivamycin, 2′,3′-dideoxytoyocamycin and 2′,3′-dideoxytriciribine is described. The key intermediate, carbocyclic 4-chloro- 5-iodopyrrolopyrimidine, was synthesized in good yield via a novel iodination method using I₂ and CF₃COOAg. This carbocyclic 4-chloro-5-iodopyrrolopyrimidine then allowed for a concise synthesis of the desired 4,5-disubstituted carbocyclic nucleosides.     

Synthesis of S-adenosyl-L-homocysteine hydrolase inhibitors and their biological activities.

Several nucleosides have been prepared as a possible inhibitor of human S-adenosyl-L-homocysteine (SAH) hydrolase for the development of anti-viral agents. Recently, SAH hydrolase has been considered as an attractive target for parasite chemotherapy for malaria. We report synthesis of several nucleosides including carbocyclic nucleosides and their inhibitory activities against recombinant malaria and human SAH hydrolases.     

Asymmetric synthesis of carbocyclic pyrimidine nucleosides via pi-allylpalladium complex

Racemic and enantiomerically pure carbocyclic pyrimidine nucleosides were synthesized efficiently by a convergent approach using Trost nucleophilic addition of pi-allylpalladium complexes.     

Synthesis and chirality analysis of carbocyclic 5'-nor nucleosides.

Achiral carbocyclic "DL-like" 5'-nor nucleosides have been synthesized and analyzed by the chiral capillary electrophoresis to elucidate the "D-like" monomers.     

Asymmetric synthesis of cyclopropyl-fused 2'-C-methylcarbanucleosides as potential anti-HCV agents

Novel 2'-C-methyl-cyclopropyl-fused carbocyclic nucleosides as potential anti-HCV agents were stereoselectively synthesized, utilizing regioselective cleavage of the isopropylidene group and cyclic sulfate chemistry as key steps.     

Carbocyclic Nucleosides: Synthesis of Analogues of Cyclobut-G

Abstract

Several carbocyclic nucleosides structurally related to Cyclobut-G have been synthesized from pinonic acid.     

Enzymatic synthesis of 2-amino- 3-hydroxy-1,6-hexanedicar☐ylic acid using serinehydroxymethyltransferase

The scale up of earlier work from these laboratories using the enzyme serinehydroxymethyltransferase has resulted in the use of this enzyme for the synthesis of 2-amino-3-hydroxy-1,6-hexanedicar☐ylic acid (7) on a preparative scale. This compound, which has been barely described in the literature, is potentially useful for the synthesis of carbocyclic β-lactams and carbocyclic nucleosides.     

ASYMMETRIC SYNTHESIS OF CARBOCYCLIC PYRIMIDINE NUCLEOSIDES VIA π-ALLYLPALLADIUM COMPLEX

Racemic and enantiomerically pure carbocyclic pyrimidine nucleosides were synthesized efficiently by a convergent approach using Trost nucleophilic addition of π-allylpalladium complexes.     

New carbocyclic nucleosides derived from indan

Seven new carbocyclic nucleosides derived from indan (1a-g) were efficiently prepared from 1,2-indanedimethanol vía Mitsunobu reaction with 6-chloroadenine and subsequent introduction of the appropriate substituent.     

Synthesis of carbocyclic analogues of MECA and NECA 1,2-disubstituted as potential adenosine receptor agonists

A new class of 1,2-disubstituted carbocyclic nucleosides of MECA and NECA analogues was synthesized in good yield starting from (+/-) 6-azabicyclo[3.2.0]heptan-7-one.     

Chiral carbocylic nucleosides: The synthesis and antiviral activity of 4′-hydroxy and 4′-fluorocarbocyclic - 2′- deoxyguanosines

The chiral carbocyclic nucleosides 2 and 3 were prepared from aristeromycin. The 4′-hydroxy compound 2 displays good antiviral activity against HSV-1 and HSV-2 with low toxicity.     

Asymmetric synthesis of novel apio carbocyclic nucleoside analogues as potential antiviral and antitumor agent

Novel apio carbocyclic nucleosides 18-21 were asymmetrically synthesized as potential antiviral and antitumor agent, starting from D-ribose employing aldol reaction, RCM reaction and Mitsunobu reaction as key reactions.