Mass spectrometric investigation of minor products in the radiolysis of liquid cyclopentane

The following substances have been identified as minor products in the gamma radiolysis of liquid cyclopentane at 3 X 10(22) eV total dose: 1,4-pentadiene; 2-pentene; cyclopentadiene; 1,3-pentadiene; ethyl cyclopentane; vinyl cyclopentane; n-heptane; n-octane; propyl cyclopentane; propenyl cyclopentane or propyl cyclopentene; n-decane; pentenyl cyclopentane or n-pentyl cyclopentene; n-pentyl cyclopentane; and cyclopentyl cyclopentene. The determination of these products was by parent mass number, gas chromatographic retention times, and/or boiling points of the compounds. Ultraviolet spectroscopic studies of the radiolysis of solutions of cyclopentadiene in cyclopentane are also described.     

Cyclopentene dialdehydes from Tabebuia impetiginosa

The isolation of two cyclopentene dialdehydes, 2-formyl-5-(4'-methoxybenzoyloxy)-3-methyl-2-cyclopentene-1-acetal dehyde, and 2-formyl-5-(3', 4'-dimethoxybenzoyloxy)-3-methyl-2-cyclopentene-1-acetaldehyde, from the bark of Tabebuia impetiginosa is reported. The structures were established by analysis of spectroscopic data. These compounds showed anti-inflammatory activity.     

Thrombomodulin induction in cultured human endothelial cells by 9-cis-locked retinoic acid analogues

9-cis-Retinoic acid (RA) analogues devised to lock the 9-cis double bond by ring formation were synthesized using two stereoselective carbon-carbon bond formation reactions as key steps. The palladium-mediated Suzuki reaction was adopted to construct a 7E-double bond (RA numbering) and the Horner-Emmons olefination was employed for stereoselective 11E-double bond (RA numbering) formation. The synthesized 9-cis-RA analogues that are locked by five-membered ring systems (cyclopentene, dihydrofuran, and dihydrothiophene) were shown to have comparable thrombomodulin induction activities to that of 9-cis RA. Conformational analysis of these compounds showed their similarity to 9-cis RA in the spatial orientation of the side chain and the terminal carboxy group.     

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 (K2CO3, 18-Crown-6, DMF) afforded the target nucleosides 12, 13, 14, and 15. In addition, the antiviral evaluations against various viruses were performed.     

Isolation and characterization of naturally occurring cyanogenic compounds

The literature dealing with the detection, isolation, purification and characterization of cyanogenic glycosides has been integrated with spectral and chemical data as well as other techniques from our laboratory to establish a method for the positive identification of glycosides of this type. The compounds are arranged into biosynthetically related groups (those derived from l-phenylalanine; l-tyrosine; l-leucine, l-valine; l-isoleucine; those with cyclopentene rings and pseudocyanogenic glycosides) and features of each of the above procedures are critically reviewed and spectral data for each group presented (IR, MS, UV and NMR). The NMR spectra of TMS ethers of cyanogenic glycosides have proven especially useful in chemical structure determination. This information is sufficient to permit identification of any of the 26 known glycosides as well as certain uncharacterized ones.     

Synthesis and structural study of pyrimidyl carbocyclic analogues of nucleosides based on cyclopentene rings

A series of 1,2-disubstituted carbonucleoside analogues of pyrimidine and 5-halopyrimidines with the unsaturated carbocycle cyclopentene was synthesized. AIM theory was applied to analyse the conformational and electronic effects of 5-halogenation.     

SAR, species specificity, and cellular activity of cyclopentene dicarboxylic acid amides as DHODH inhibitors

Novel DHODH inhibitors were developed based on a previously described series by introduction of heteroatoms into the cyclopentene ring and hydroxyl groups attached to it. Also, the hydrophobic biphenyl side chain was replaced with benzyloxy phenyl groups. Activities on human, rat, and mouse enzymes indicate a species specificity of these inhibitors.     

SYNTHESIS AND STRUCTURAL STUDY OF PYRIMIDYL CARBOCYCLIC ANALOGUES OF NUCLEOSIDES BASED ON CYCLOPENTENE RINGS

A series of 1,2-disubstituted carbonucleoside analogues of pyrimidine and 5-halopyrimidines with the unsaturated carbocycle cyclopentene was synthesized. AIM theory was applied to analyse the conformational and electronic effects of 5-halogenation.     

Synthesis and conformational analysis of a locked analogue of carbovir built on a bicyclo[3.1.0]hex-2-enyl template

The synthesis and biological evaluation of a carbovir analogue (5) built on a bicyclo[3.1.0]hex-2-enyl template is described. A conformational analysis using density functional theory at the B3LYP/6-31G* level has been carried out on the rigid pseudosugar template of 5, the cyclopentene moiety of carbovir and the bicyclo[3.1.0]hex-2-yl pseudosugars of two isomeric carbonucleosides (12 and 13) containing exo- and endo-fused cyclopropane rings. The results show that while the planar configuration of the fused cyclopentane ring of compound 5 helps retain weak anti-HIV activity, the ability of the cyclopentene ring of carbovir to easily adopt a planar or puckered conformation with little energy penalty may prove to be a crucial advantage. The bicyclo[3.1.0]hex-2-yl nucleosides 12 and 13 that were inactive against HIV exhibited stiffer resistance to having a planar, fused cyclopentane moiety.     

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 of novel hydroxymethyl substituted analogues related to carbovir and neplanocin A

Two enantiomerically pure hydroxymethyl substituted cyclopentene nucleoside analogues (42 and 53) related to carbovir and neplanocin A, respectively, were prepared from the chiral pool of iridoid glucosides. In addition two saturated hydroxymethylated analogues (44 and 45) were obtained from a protected intermediate.     

Synthesis and SAR of 1,3-disubstituted cyclohexylmethyl urea and amide derivatives as non-peptidic motilin receptor antagonists

A series of 1,3-disubstituted cyclohexylmethyl urea and amide derivatives were synthesized as motilin receptor antagonists. Starting from known motilin antagonists, 1a and 1b, the cyclopentene scaffold was replaced and the four recognition elements optimized to arrive at a potent novel series.     

One-dimensional structure of a photochromic coordination polymer composed of 1,2-bis[2-methyl-5-(4-pyridyl)-3-thienyl]cyclopentene and Zn(II) chloride

The crystal structure of the coordination polymer composed of 1,2-bis[2-methyl-5-(4-pyridyl)-3-thienyl]cyclopentene and Zn(II) chloride has been determined at 293 K. The photochromic ligand coordinates to the Zn cations adopting a C₂ symmetry geometry. The distance between the central reaction carbons is short enough to undergo photochromic reaction.     

Occurrence and biosynthesis of cyclopentenyl fatty acids in leaves and chloroplasts of flacourtiaceae

Cyclopentenyl fatty acids, the unusual fatty acids occurring naturally in certain Flacourtiaceae, have been detected for the first time in leaves of various plants belonging to the tribes Pangieae, Oncobeae and Flacourtieae. In leaves and chloroplasts of Caloncoba echinata (Oncobeae) cyclopentenyl fatty acids are synthesized from aspartate plus pyruvate or glutamate plus acetate. The biogenesis of the cyclopentene ring occurs from a C₇, compound, that may be formed by either pair of substrates.     

Synthesis and Anti-HCV Activity of 4-Methoxy-7H-Pyrrolo[2,3-d] Pyrimidine Carbocyclic Nucleosides

The present study includes the exploration of new possible nucleoside mimetics based on 4-methoxy-7H-pyrrolo[2,3-d]pyrimidine carbocyclic nucleosides (4a–g), which were synthesized by 10–15 synthetic steps and characterized adequately. We report the anti-HCV activities and cytotoxicities of 4a–g. Compound 4a was analyzed by single crystal X-ray diffraction which showed some puckering in the cyclopentene ring with a 2′-endo conformation and anti-base disposition (χ = ?125.7°).     

Synthesis and Conformational Analysis of a Locked Analogue of Carbovir Built on a Bicyclo[3.1.0]-hex-2-enyl Template

Abstract

The synthesis and biological evaluation of a carbovir analogue (5) built on a bicyclo[3.1.0]hex-2-enyl template is described. A conformational analysis using density functional theory at the B3LYP/6-31G* level has been carried out on the rigid pseudosugar template of 5, the cyclopentene moiety of carbovir and the bicyclo[3.1.0]hex-2-yl pseudosugars of two isomeric carbonucleosides (12 and 13) containing exo- and endo-fused cyclopropane rings. The results show that while the planar configuration of the fused cyclopentane ring of compound 5 helps retain weak anti-HIV activity, the ability of the cyclopentene ring of carbovir to easily adopt a planar or puckered conformation with little energy penalty may prove to be a crucial advantage. The bicyclo[3.1.0]hex-2-yl nucleosides 12 and 13 that were inactive against HIV exhibited stiffer resistance to having a planar, fused cyclopentane moiety.     

Enzymatic synthesis of Q* nucleoside containing mannose in the anticodon of tRNA: isolation of a novel mannosyltransferase from a cell-free extract of rat liver

The Q nucleosides isolated from rabbit liver tRNA are known to have sugars (mannose or galactose) linked to their cyclopentene diol moiety. A Q nucleoside containing mannose (manQ) was synthesized by a cell-free system from rat liver, using purified E. coli tRNAAsp as an acceptor and GDP-mannose as a donor molecule. The novel mannosyltransferase catalyzing this reaction was purified from a particulate-free soluble enzyme fraction and found to be strictly specific for tRNAAsp. These results, together with the anomeric configuration of mannose in Q nucleoside, indicate that no lipid intermediate is involved in the biosynthesis of Q nucleoside.     

Substrate and inhibitor specificity of tRNA-guanine ribosyltransferase

We have tested as inhibitors or substrates of tRNA-guanine ribosyltransferase (EC 2.4.2.29) a number of compounds, including derivatives of 7-deazaguanine, pteridines, purines, pyrimidines and antimalarials. Virtually all purines and pteridines that are inhibitors or substrates of the rabbit reticulocyte enzyme have an amino nitrogen at the 2 position. In addition the 9 position and the oxygen at the 6 position may be important for recognition by the enzyme. Saturation of the double bond in the cyclopentenediol moiety of queuine reduces substrate activity and queuine analogs that lack the cyclopentenediol moiety, such as 7-deazaguanine and 7-aminomethyl-7-deazaguanine, are relatively poor substrates for the enzyme. While adenosine is not an inhibitor, neplanocin A (an adenosine analog in which a cyclopentenediol replaces the ribose moiety) is a poor inhibitor. The incorporation of 7-aminomethyl-7-deazaguanine into the tRNA of L-M cells results in a novel chromatographic form of tRNAAsp, indicating that L-M cells cannot modify this Q precursor (in Escherichia coli) to queuosine. The specific incorporation of 7-deazaguanine and 8-azaguanine into tRNA by L-M cells also results in novel chromatographic forms of tRNAAsp. With intact L-M cells, the enzyme-catalyzed insertion into tRNA of queuine, dihydroqueuine, 7-aminomethyl-7-deazaguanine, or 7-deazaguanine is irreversible, while guanine or 8-azaguanine incorporation is reversible; suggesting that it is the substitution of C-7 for N-7 which prevents the reversible incorporation of queuine into tRNA.     

Rational design of conformationally restricted quinazolinone inhibitors of poly(ADP-ribose)polymerase

A successful design of conformationally restricted novel quinazolinone derivatives linked via a cyclopentene moiety as potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors has been developed. One selected member of the new series, 8-chloro-2-[(3S)-3-(4-phenylpiperidin-1-yl)cyclopent-1-en-1-yl]quinazolin-4(3H)-one (S-16d), was found to be highly potent with IC(50)=8.7 nM and good brain penetration.     

Diazo- and azido-functionalized glutaraldehydes as cross-linking reagents and potential fixatives for electron microscopy

The synthesis of diazo and perfluorophenyl azide (PFPA) functionalized glutaraldehydes 7 and 13a-d as new cross-linking reagents for bioconjugation and potential fixatives for electron microscopy is reported. A key step is the generation of the 1,5-dialdehyde structures by oxidative cleavage of the corresponding cyclopentene epoxide using HIO4 in aqueous tetrahydrofuran. A model reaction between 3-substituted glutaraldehyde 14 and 6-aminohexanoic acid resulted in the formation of pyridinium ion containing products with UV spectra comparable to those observed with glutaraldehyde itself. Thus modification of glutaraldehyde in the 3-position most probably did not significantly change its reactivity with amines under chemical-fixation conditions. Fixation of red blood cells by 7 demonstrates that as a fixative, 7 is comparable to glutaraldehyde.