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.     

Stereoselective synthesis of 3-hydroxymethyl-D-cyclopentenone, the versatile intermediate for the synthesis of carbocyclic nucleosides

The preparative and stereoselective synthesis (45- 50% overall yields, >50 g scale) of the key carbasugars 7a-d was achieved from D-ribose via stereoselective Grignard reaction and oxidative rearrangement as key reactions.     

Synthesis of carbocyclic purine nucleosides using key intermediates, carbocyclic AICA-ribosides

Treating carbocyclic N1-methoxymethy-inosine and 2'-deoxy-inosine with 1N-NaOH/aq.EtOH gave the carbocyclic 5-amino-4-imidazolecarboxamide-riboside and -2'-deoxyriboside respectively. Reaction of both useful key intermediates with PhCONCS afforded the corresponding 5-(N-isothiocarbamoyl) derivatives in high yield. Methylation of the isothiocarbamoyl groups, followed by treatment with NaOH led to the purine ring-closure (guanine, isoguanine, and xanthosine) reaction.     

The latest progress in the synthesis of carbocyclic nucleosides

This review presents the latest developments in the field of carba-nucleosides (1994-1998). Special attention is paid to the synthesis of key precursors to those carba-nucleosides that possess significant biological activities or have novel structures.     

New fluorinated carbocyclic nucleosides: synthesis and bioactivity

Novel fluorinated carbocyclic nucleosides, (+-)-3'-deoxy-3'-fluoroaristeromycin and (+-)-2',3'-dideoxy-3'-fluoroaristeromycin have been synthesized. The antitumor activities of these compounds were studied.     

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.     

Novel synthesis of carbocyclic nucleosides from 2-azabicyclo[2.2.1]heptanes via the reductive N2-C3 cleavage reaction as a key step

Carbocyclic ribofuranosyl and arabinofuranosyl pyrimidine nucleosides were synthesized stereoselectively from 2-azabicyclo[2.2.1]hept-5-en-3-one via NaBH4 promoted C-N bond cleavage reaction as a key step.     

Practical Synthesis of D-Cyclopent-2-enone,the Key Intermediate of Carbocyclic Nucleosides

Abstract

An efficient and practical method for the synthesis of (4R,5R)-4,5-O-isopropylidene-cyclopent-2-enone was developed from D-ribose by using a ring-closing metathesis reaction.     

High pressure mediated Diels-Alder reaction using 2-iminomalonates as dienophiles: novel synthesis of carbocyclic nucleosides.

9-[c-4-(1,2-Dihydroxyethyl)cyclopent-2-en-r-1-yl]-9H-adenine , an isomer of BCA, has been synthesized from Diels-Alder adducts prepared by the reaction of 2-iminomalonates with cyclopentadiene under high pressure. The synthetic method involves a novel C-N bond cleavage reaction by NaBH4-K2CO3 (RRA reaction conditions) and has wide applicability for the synthesis of various carbocyclic nucleosides.     

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.     

Synthesis and biological activity of novel carbocyclic nucleosides

The syntheses of several novel carbocyclic nucleosides which incorporate the cyclopentene moiety of neplanocin A will be presented. These include modified pyrimidine derivatives of the very potent antitumor agent cyclopentenyl cytosine and carbocyclic analogues of the ketohexose nucleosides psicofuranine and psicofuranosyl cytosine.     

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.     

Synthesis of carbocyclic nucleosides bearing a cyclopropane ring.

A carbocyclic cyclopropane fused nucleoside, 9-(c-4-hydroxymethylbicyclo[3.1.0]hex-r-2-yl)-9H-adenine, has been efficiently synthesized from 2-azabicyclo-[2.2.1]hex-5-en-3-one (ABH) in 6 steps, namely cyclopropanation, -reductive amide cleavage (RAC) reaction and adenine ring construction.     

Facile synthesis of 1',2'-cis-beta-pyranosyladenine nucleosides

1',2'-cis-beta-Glycosyladenine nucleosides, such as beta-altroside, beta-mannoside, and beta-idoside, were efficiently synthesized from the corresponding 1',2'-trans-beta-6-chloropurine derivatives, beta-glucoside, and beta-galactoside. Nucleophilic substitution of the O-trifluoromethanesulfonyl groups at the C-2' and/or 3' was carried out using tetrabutylammonium acetate or cesium acetate under mild conditions. Subsequent deprotection and amidation afforded the desired compounds, 1',2'-cis-beta-pyranosyladenine nucleosides.     

Synthesis and biological evaluation of novel homochiral carbocyclic nucleosides from 1-amino-2-indanols

New chiral purinyl and 8-azapurinyl carbanucleoside derivatives based on indanol were synthesized from commercial available (1S,2S)-trans-1-amino-2-indanol and (1R,2R)-trans-1-amino-2-indanol using a linear methodology. The antiviral activity and cytotoxicity of these compounds were evaluated against herpes simplex virus type 1 (HSV-1) in Vero cells, bovine viral diarrhea virus (BVDV) in Mardin-Darby bovine kidney (MDBK) cells and hepatitis B virus (HBV) in HepG2 2.2.15 cell line. Three compounds, showed an inhibition of the HBsAg levels similar to reference drug lamivudine. One chloropurinyl nucleoside, derived from the cis-1-amino-2-indanol, was cytotoxic on MDBK cells and it could be a lead for developing anticancer agents.     

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.     

1-O-benzyl-2-O-methyl-rac-glycerol: a key intermediate for synthesis of ether glycerolipids.

A new scheme for synthesis of saturated 1-O-alkyl-2-O-methyl-rac-glycerolipids is described. The reductive cleavage of 2-O-methyl-1,3-O,O-benzylideneglycerol with BH3.THF complex leads to 1-O-benzyl-2-O-methyl-rac-glycerol, which is a key in intermediate for the facile preparation of 1-O-alkyl-2-O-methyl-rac-glycerol and derivatives.     

Squarate-based carbocyclic nucleosides: Syntheses,computational analyses and anticancer/antiviral evaluation

Squaric acid and its derivatives are versatile synthons and have demonstrated applications in medicinal chemistry, notably as non-classical bioisosteric replacements for functional groups such as carboxylic acids, alpha-amino acids, urea, guanidine, peptide bonds and phosphate/pyrophosphate linkages. Surprisingly, no reports have appeared concerning its possible application as a nucleobase substitute in nucleosides. A preliminary investigation of such an application is reported herein. 3-Amino-4-((1R,4S)-4-(hydroxymethyl)cyclopent-2-en-1-yl)amino-cyclobut-3-ene-1,2-dione, 3-((1R,4S)-4-(hydroxymethyl)cyclopent-2-en-1-yl)amino-4-methoxycyclobut-3-ene-1,2-dione, and 3-hydroxy-4-((1R,4S)-4-(hydroxymethyl)cyclopent-2-en-1-yl)amino-cyclobut-3-ene-1,2-dione sodium salt were synthesized. Computational analyses of their structures and preliminary antitumor and antiviral screening results are reported.     

Synthesis of carbocyclic nucleosides and their SAH hydrolase inhibitory activities.

The cellular enzyme S-adenosyl-L-homocysteine (SAH) hydrolase has emerged as a target enzyme for the molecular design of anti-viral agents. Recently, SAH hydrolase has been considered as an attractive target in parasite chemotherapy for malaria. We report synthesis of several carbocyclic purine nucleosides and their inhibitory activities against human and malaria recombinant SAH hydrolases.