Showing papers on "Substituent published in 1994"

New type of linkage between a carbohydrate and a protein: C-glycosylation of a specific tryptophan residue in human RNase Us

Abstract: We report a new type of linkage between a carbohydrate and a protein, involving the rarely modified side chain of a tryptophan residue. An aldohexopyranosyl residue was found to be linked via a C-C bond to the indole ring of the tryptophan residue at position 7 of human RNase Us. Mass spectrometric analysis of peptides containing this residue showed a molecular mass 162 Da higher than that expected for tryptophan. The fragmentation pattern of the modified amino acid side chain was reminiscent of that of aromatic C-glycosides, suggesting a direct attachment of a hexose residue to a C-position of the tryptophan indole moiety. 1H and 13C NMR spectroscopic data confirmed this inference and unequivocally demonstrated the substituent to be an aldohexopyranosyl residue, C-glycosidically linked to the C2 atom of the indole. This mode of attachment differs from the ones known so far, in which carbohydrates are linked to an amino acid side chain by N- or O-glycosidic bonds.

Dibenzopyrrometheneboron difluoride dyes

Abstract: The invention relates to fluorescent dyes that are substituted or unsubstituted derivatives of 1-[isoindolyl]methylene-isoindole that are bound through both isoindole nitrogens to a boron difluoride moiety, forming a fluorescent dibenzopyrrometheneboron difluoride compound ##STR1## whose fluorescence properties are modified by the selection of appropriate chemical substituents. The dibenzopyrrometheneboron difluoride compound is optionally substituted by hydrogen, halogen cyano, sulfo, alkali or ammonium salts of sulfo, carboxy, substituted or unsubstituted alkyl, perfluoroalkyl, alkoxy, alkylthio, nitro, amino, monoalkylamino, dialkylamino, substituted or unsubstituted aryl substituents, substituted or unsubstituted heteroaryl substituents, or additional substituted or unsubstituted fused benzo rings or substituted or unsubstituted fused heteroaromatic rings. Any alkyl substituent present on the subject dye is optionally further substituted by a reactive site, or a functional group that can be readily converted into a reactive site.

Cyclic-substituted unsymmetrical cyanine dyes

Abstract: The invention describes the preparation and use of fluorescent stains for nucleic acids derived from unsymmetrical cyanine dyes comprising a substituted benzazolium ring system linked by a methine bridge to a pyridinium or quinolinium ring system having at least one substituent that is a saturated or unsaturated cyclic substituent. Superior fluorescent characteristics when complexed with nucleic acids give the dyes utility for the detection of oligonucleotides and nucleic acids in cells, gels, and solutions. The presence of the cyclic substituent results in improved permeability in a wide range of cells and gels, resulting in improved detection of nucleic acids. Combination with additinal dyes permits analysis of cell membrane integrity, Gram sign, or cell structure and function.

Structure-Activity Relationships in the Oxidation of Benzylamine Analogs by Bovine Liver Mitochondrial Monoamine Oxidase B

Abstract: The influence of para and meta substitution of benzylamine on its interaction with bovine liver mitochondrial monoamine oxidase B (MAO B) has been investigated by steady-state and reductive half-reaction anaerobic stopped-flow kinetic approaches. Steady-state kinetic properties of each benzylamine analogue suggest that para or meta substitution does not alter the mechanistic pathway of catalysis [Husain, M., et al. (1982) Biochemistry 21, 595-600]. All analogues tested exhibited Dkcat values ranging from 5.5 to 8.9 and D[kcat/Km(amine)] values ranging from 3.3 to 8.1 D[kcat/Km(O2)] values of approximately 1 are observed for all substrate analogues. Values for Kd were calculated from steady-state isotope effect data [Klinman, J.P., & Matthews, R.G. (1985) J. Am. Chem. Soc. 107, 1058-1060] and are in good agreement with Ks values determined from analysis of the rate of MAO B reduction as a function of benzylamine analogue concentration in reductive half-reaction experiments. A linear correlation of benzylamine analogue Kd values with the hydrophobicity parameter (phi) is observed for the para-substituted analogues where the binding affinity increases with increasing hydrophobicity of the substituent. Statistical treatment of the correlation shows a small negative contribution to binding by the van der Waals volume (VW) of the para substituent. meta-Substituted benzylamine analogues show a decreased binding affinity with the VW of the substituent and no correlation with the hydrophobicity value of the substituents tested. No spectral evidence was found for any flavin radical intermediates during the time course of MAO B flavin reduction in anaerobic reductive half-reduction stopped-flow experiments with any of the alpha,alpha-diprotio- or alpha,alpha-dideuteriobenzylamine analogues tested. The limiting rates of enzyme reduction exhibit large Dk values (6.5-14.1) for all of the analogues tested. para-Substituted benzylamine analogues reduce MAO B with limiting rates that correlate with the steric influence (Es value) of the substituent. Statistical analysis shows the rate of MAO B reduction by para-substituted analogues to be retarded by increased values of Es and, with a smaller contribution, by the hydrophobicity value of the substituent. The rate of MAO B reduction by meta-substituted benzylamine analogues is essentially independent of the nature of the substituent. No evidence was found for any electronic contribution to the rate of MAO B flavin reduction by any of the analogues tested. These data demonstrate the steric orientation of the substrate to be important in the rate of amine oxidation by MAO B and that ring meta substituents favor this orientation.(ABSTRACT TRUNCATED AT 400 WORDS)

Diels-Alder Reactions in Water. Effects of Hydrophobicity and Hydrogen Bonding

Abstract: In order to check whether the activated complex for the Diels-Alder reactions of 5-substituted 1,4-naphthoquinones with cyclopentadiene is more polar in water than in other solvents, we have determined the substituent effects in seven different solvents. The substituent effects gradually decrease with increasing rate of the reaction in a specific solvent, indicating that the charge separation in the activated complex in water is not much different from that in the other solvents. We also compared solvent effects on the Diels-Alder reaction of methyl vinyl ketone with cyclopentadiene with effects on the corresponding reaction of methyl vinyl sulfone. The medium effects were separated into effects on initial state and activated complex. The destabilization of the initial state by water and the stabilization of the activated complex by 2,2,2-trifluoroethanol were less pronounced for the sulfone than for the ketone. These results further underline the importance of enforced hydrophobic interactions and changes in hydrogen bonding during the activation process in explaining the acceleration of Diels-Alder reactions in water.

Chemistry of Enoxysilacyclobutanes - Highly Selective Uncatalyzed Aldol Additions

Abstract: O(Silacyclobuty1) ketene acetals derived from esters, thiol esters, and amides underwent facile aldol addition with a variety of aldehydes at room temperature without the need for catalysts. The uncatalyzed aldol addition reaction of O(silacyclobuty1) ketene acetals displayed the following characteristics: (1) the rate of reaction was highly dependent on the spectator substituent on silicon and the geometry of the ketene acetal, (2) the 0,O-ketene acetal of E configuration afforded the syn aldol products with high diastereoselectivity (93/7 to 99/1), (3) conjugated aldehydes reacted more rapidly than aliphatic aldehydes, and (4) the reaction was mildly sensitive to solvent. In addition, the aldol reaction was found to be efficiently catalyzed by metal alkoxides. Labeling experiments revealed that the thermal aldol reaction proceeds by direct intramolecular silicon group transfer, while the alkoxide-catalyzed version probably proceeds via in situ generated metal enolates. Computational modeling of the transition states suggests that the boat transition structures are preferred, supporting the observed syn selectivity of the thermal aldol reaction. Both thermal and alkoxide-catalyzed Michael additions were investigated, revealing a competition between 1,2- and 1 ,Caddition favoring the former.

.pi.-Conjugated Soluble Poly(aryleneethynylene) Type Polymers. Preparation by Palladium-Catalyzed Coupling Reaction, Nonlinear Optical Properties, Doping, and Chemical Reactivity

Abstract: Palladium-catalyzed polycondensation between dihalo aromatic compounds X-Ar-X (3-hexyl-2,5-diiodothiophene, 2,5-dibromoselenophene, and 3,4-dinitro-2,5-dibromothiophene) and diethynyl aromatic compounds HC≡C-Ar'-C≡CH (2,5-diethynylpyridine, 3-hexyl-2,5-diethynylthiophene, and p-diethynylbenzene) in the presence of triethylamine gives soluble π-conjugated poly(aryleneethynylene) (PAE) type polymers (-Ar=C≡C-Ar'-C≡C-) n when Ar and/or Ar' contains the long alkyl substituent and/or pyridine ring

Design of inhibitors of glycogen phosphorylase: a study of alpha- and beta-C-glucosides and 1-thio-beta-D-glucose compounds.

Abstract: alpha-D-Glucose is a weak inhibitor of glycogen phosphorylase b (Ki = 1.7 mM) and acts as a physiological regulator of hepatic glycogen metabolism. Glucose binds to phosphorylase at the catalytic site and results in a conformational change that stabilizes the inactive T state of the enzyme, promoting the action of protein phosphatase 1 and stimulating glycogen synthase. It has been suggested that, in the liver, glucose analogues with greater affinity for glycogen phosphorylase may result in a more effective regulatory agent. Several alpha- and beta-anhydroglucoheptonic acid derivatives and 1-deoxy-1-thio-beta-D-glucose analogues have been synthesized and tested in a series of crystallographic and kinetic binding studies with glycogen phosphorylase. The structural results of the bound enzyme-ligand complexes have been analyzed, together with the resulting affinities, in an effort to understand and exploit the molecular interactions that might give rise to a better inhibitor. This work has shown the following: (i) Similar affinities may be obtained through different sets of interactions. Specifically, in the case of the alpha- and beta-glucose-C-amides, similar Ki's (0.37 and 0.44 mM, respectively) are obtained with the alpha-anomer through interactions from the ligand via water molecules to the protein and with the beta-anomer through direct interaction from the ligand to the protein. Thus, hydrogen bonds through water can contribute binding energy similar to that of hydrogen bonds directly to the protein. (ii) Attempts to improve the inhibition by additional groups did not always lead to the expected result. The addition of nonpolar groups to the alpha-carboxamide resulted in a change in conformation of the pyranose ring from a chair to a skew boat and the consequent loss of favorable hydrogen bonds and increase in the Ki. (iii) The addition of polar groups to the alpha-carboxamide led to compounds with the chair conformation, and in the examples studied, it appears that hydration by a water molecule may provide sufficient stabilization to retain the chair conformation. (iv) The best inhibitor was N-methyl-beta-glucose-C-carboxamide (Ki = 0.16 mM), which showed a 46-fold improvement in Ki from the parent beta-D-glucose. The decrease in Ki may be accounted for by a single hydrogen bond from the amide nitrogen to a main-chain carbonyl oxygen, an increase in entropy through displacement of a water molecule, and favorable van der Waals contacts between the methyl substituent and nonpolar protein residues.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of the substituent pattern of heterogeneously and homogeneously synthesized carboxymethyl cellulose by using high-performance liquid chromatography

Abstract: A rapid and convenient procedure was developed for the determination of the substituent pattern of carboxymethyl cellulose (CMC) by means of high-performance liquid chromatography. The hydrolysates of CMC are separated on a polystyrene-based strong cation-exchange resin into glucose, 2,3,6-tri-O-carboxymethyl glucose and groups of 2-, 3-and 6-mono-O- and 2,3-, 2,6-, and 3,6-di-O-carboxymethyl glucoses. By this method the determination of the average degree of substitution as well as the substituent pattern is possible. In this way we found that CMC samples which were synthesized in LiCl/N,N-dimethylacetamide as a cellulose solvent, contain a significantly higher amount of both tricarboxymethylated and unsubstituted units than those obtained in a slurry of cellulose in isopropanol/water at comparable DS values. The substituent pattern of heterogeneously synthesized CMC is mainly determined by statistics.

Stereo- and enantioselective alternating copolymerization of [alpha]-olefins with carbon monoxide -- Synthesis of chiral polymers

Abstract: Palladium(II) compounds of the type [PdL[sub 2](MeCN)[sub 2](MeCN)[sub 2]](BF[sub 4])[sub 2](L[sub 2] = chiral bidentate ligand) have been used as catalysts for the synthesis of chiral alternating [alpha]-olefin-carbon monoxide copolymers. For the synthesis of the chiral propylene-carbon monoxide copolymer and the ethylene-propylene-carbon monoxide terpolymer, chiral bidentate phosphines were employed as the ligand. The alternating styrene-carbon monoxide copolymers made thus far have been highly syndiotactic and since isotactic segments in the polymer backbone were required for chirality, a new ligand system was needed. When 2-pyridinecarboxaldehydeimine derivatives were used as the bidentate ligand, the ratio of isotactic to syndiotactic segments in the styrene-carbon monoxide copolymers was found to increase with increasing steric size of the substituent on the imine nitrogen, and when the enantiomerically pure 2-pyridinecarboxaldehyde-N-[alpha]-methylbenzylimine was employed, chiral alternating styrene-carbon monoxide copolymers were obtained. Finally, it appears that the optical rotations of the chiral copolymers were primarily due to the presence of stereogenic tertiary carbon centers in the polymer backbone with only minimal contribution from polymer conformation.

Synthesis of polyphenylenes and polynaphthalenes by thermolysis of enediynes and dialkynylbenzenes

Abstract: : Described are the syntheses of substituted enediynes and dialkynylbenzenes using Pd- or Pd/Cu-catalyzed cross coupling procedures. The products were then thermalized, generally in benzene, to afford the corresponding poly(p-phenylene)s and poly(1,4-naphthalene)s. Thirteen examples are provided that show the scope of the polymerization process based upon substituent patterns and cyclization moieties. The superb thermal resiliency of the newly derived polymers is demonstrated using thermogravimetric analysis. The polymer structure was generally confirmed using IR data correlations to small molecules that resembled the polymer's repeat unit structure. Radical trapping of dimeric intermediates, that were analyzed by GCMS, further substantiated the proposed mechanistic route. The step-growth polymerization pattern was determined by monitoring the degree of monomer consumption versus the polymer molecular weight.

Recovery of Metals from Aqueous Media by Extraction with Supercritical Carbon Dioxide

Abstract: Measurements of solubilities in supercritical CO 2 corroborated the hypothesis that the nonpolar character of a series of tetraalkylammonium dialkyldithiocarbamate ion pairs was influenced (i) primarly by the chain length of the alkyl substituent on the carbamate nitrogen and (ii) to a lesser extent, by the chain length of the alkyl substituent(s) on the ammonium counterion. Similarly, the solubility of Zn-dithiocarbamate complexes decreased in the order dibutyl (DBDTC)>diethyl >pyrrolidine. An extraction protocol in which SC-CO 2 was saturated with tetrabutylammonium DBDTC prior to dynamic complexation/mobilization of 12-20 μg/mL Zn, Cd, or Pb analyte from aqueous solution resulted in >73% and >94% analyte removal within 5 and 15 min extraction, respectively

Polyethylene compatible sulphonic acids as silane crosslinking catalysts

Abstract: A crosslinkable polymer composition contains a crosslinkable polymer with hydrolysable silane groups and at least one silanol condensation catalyst. The polymer composition is distinguished by the silanol condensation catalyst being a compound of the formula ArSO3H (I) or a precursor thereof, Ar being a substituted benzene or naphthalene ring, the substituent or substituents containing 4-20 carbon atoms, preferably 10-18 carbon atoms. The precursor may be an anhydride of the sulphonic acid of formula (I), or a sulphonic acid of formula (I) provided with a hydrolysable protective group, e.g. an acetyl group. Specific examples of compounds of formula (I) are dodecyl benzene sulphonic acid and tetrapropyl benzene sulphonic acid.

How Does the Electronegativity of the Substituent Dictate the Strength of the Gauche Effect

Abstract: The distinct conformational preferences observed for the pentofuranosyl moieties in various 3'-substituted 2',3'-dideoxythymidine derivatives are closely related to the strength of the 3'-gauche effect, which is directly dictated by the electronegativity of the 3'-substituent. The efficiency of the 3'-gauche effect can now be quantitatively calculated with the help of simple linear calibration curves that correlate the gauche effect enthalpy AH^^") and the group electronegativity (x) of the 3'-substituent.

Carbon-13 NMR Chemical Shifts in Structural and Stereochemical Analysis

Abstract: Substituent effect correlations on the origin and stereochemical connections of the substituent effects conformational and configurational analysis and substituent effects on the 13C NMR chemical shifts of alicyclic compounds structural and stereochemical analysis of four- and five-, and seven-membered cyclanes and some other systems on the origin of stereoelectronic substituent effects 13C chemical shifts as probes in configurational and conformational analysis dynamic NMR spectroscopy and frozen spectra application of 13C NMR spectroscopy to the configurational and conformational analysis of natural products, organometallic compounds, and synthetic polymers application of other NMR parameters in combination with the 13C chemical shift in conformational and configurational analysis.

Hypolipidaemic condensed 1,4-thiazepines

Abstract: The invention provides a compound of formula (I), wherein n is an integer of from 0 to 2; R is an optional substituent; R1 is hydrogen or C?1-6?alkyl; R?2? is an atom or group selected from hydrogen, C?1-6?alkyl (including cycloalkyl and cycloalkylalkyl), C1-4alkoxy, pyrryl, thienyl, pyridyl, 1,3-benzodioxolo, phenyl and naphthyl, which groups are optionally substituted; R?3? is hydrogen, OH, C?1-6?alkyl, C1-6alkoxy or -OC1-6acyl; R?4? is a group independently selected from C?1-6?alkyl (including cycloalkyl and cycloalkylalkyl), C2-6alkenyl, and C2-6alkynyl which groups are optionally substituted; R?5? is a group independently selected from C?2-6?alkyl (including cycloalkyl and cycloalkylalkyl), C2-6alkenyl and C2-6alkynyl, which groups are optionally substituted; or R?4 and R5?, together with the carbon atom to which they are attached, form a C?3-7?spiro cycloalkyl group which is optionally substituted; R?6 and R7? are independently selected from hydrogen and C?1-6?alkyl; and X is an aromatic or non-aromatic monocyclic or bicyclic ring system having from 5 to 10 carbon atoms (including the two carbon atoms forming part of the thiazepine ring) wherein optionally one or more of the carbon atoms is/are replaced by heteroatom(s) independently selected from nitrogen, oxygen and sulphur; or X is an aromatic or non-aromatic monocyclic or bicyclic ring system having from 5 to 10 carbon atoms (including the two carbon atoms forming part of the thiazepine ring) wherein one or more of the carbon atoms is/are replaced by heteroatom(s) independently selected from nitrogen, oxygen and sulphur; and salts, solvates and physiologically functional derivatives thereof, pharmaceutical formulations comprising such compounds, processes for their preparation and their use in reducing bile acid uptake and hence as hypolipidaemic compounds.

A remarkable substituent effect on the enantioselectivity of tandem asymmetric epoxidation and enantiospecific ring expansion of cyclopropylidene alcohols: a new enantiocontrolled synthesis of (-)-debromoaplysin and (-)-aplysin

Abstract: A remarkable substituent effect by the tert-butyldimethylsiloxy group on the enantioselectivity of the tandem asymmetric epoxidation and enantiospecific ring expansion of 2-[2-(tert-butyldimethylsiloxy)-4-methylphenyl]-2-cyclopropylideneethanol (18), affording (S)-(-)-2-[2-(tert-butyldimethylsiloxy)-4-methylphenyl]-2-hydroxymethylcyclobutanone (21) in high yield and high enantiomeric excess, was observed. This enabled us to accomplish a concise and highly enantioselective total synthesis of (-)-debromoaplysin (2) and (-)-aplysin (1), providing a new and general strategy for the enantioselective synthesis of biologically important substances having the dihydrobenzofuran framework

Retinobenzoic Acids. 6. Retinoid Antagonists with a Heterocyclic Ring

Abstract: Several candidate retinoid antagonists were designed on the basis of the ligand superfamily concept and synthesized. Retinoidal activities of these benzimidazole and benzodiazepine derivatives were examined by assay of differentiation-inducing activity on human promyelocytic leukemia cell line HL-60. The parent benzimidazole derivative, 4-(5,6,7,8-tetrahydro-5,5,8,8- tetramethylnaphth-[2,3-d]imidazol-2-yl)benzoic acid (7a), and related compounds with a small alkyl group instead of the hydrogen on the nitrogen (1N) atom of the imidazole ring exhibited retinoidal activity, and the potency strongly depended on the bulkiness of the substituent. The compounds having a phenyl or benzyl group on the nitrogen lacked differentiation-inducing activity on HL-60 cells and acted as antagonists to the potent retinoid 4-[(5,6,7,8-tetrahydro-5,5,8,8- tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid (Am80). Among the compounds possessing a seven-membered heterocyclic ring as a linking group, 4-(5H-7,8,9,10-tetrahydro-5,7,7,10,10- pentamethylbenzo[e]- naphtho[2,3-b][1,4]diazepin-13-yl)benzoic acid (16) also exhibited the antagonistic activity. The binding abilities of these compounds to retinoic acid receptors alpha and beta were consistent with their potency for the inhibition of HL-60 cell differentiation induced by the retinoid Am80.

Process for the preparation of baccatin iii analogs bearing new c2 and c4 functional groups

Abstract: Process for the preparation of a derivative or analog of baccatin III or 10-desacetyl baccatin III having a C2 substituent other than benzoate and/or a C4 substituent other than acetate in which the C2 benzoate substituent and/or the C4 acetate substituent of a derivative of baccatin III or 10-desacetyl baccatin III is/are selectively reduced or hydrolyzed to the corresponding hydroxy group(s) and converted to R31COO- and/or R30COO-, respectively, wherein R30 and R31 are independently H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, monocyclic aryl or monocyclic heteroaryl.

The Chloroperoxidase-Catalyzed Oxidation of Phenols. Mechanism, Selectivity, and Characterization of Enzyme-Substrate Complexes

Abstract: The reactivity of a series of para-substituted phenolic compounds in the peroxidation catalyzed by chloroperoxidase was investigated, and the results were interpreted on the basis of the binding characteristics of the substrates to the active site of the enzyme. Marked selectivity effects are observed. These operate through charge, preventing phenolic compounds carrying amino groups on the substituent chain to act as substrates for the enzyme, and through size, excluding potential substrates containing bulky substituents to the phenol nucleus. Also, chiral recognition is exhibited by chloroperoxidase in the oxidation of N-acetyltyrosine, where only the L isomer is oxidized. Kinetic measurements show that, in general, the efficiency of chloroperoxidase in the oxidation of phenols is lower than that of horseradish peroxidase. Paramagnetic NMR spectra and relaxation rate measurements of chloroperoxidase-phenol complexes are consistent with binding of the substrates close to the heme, in the distal pocket, with the phenol group pointing toward the iron atom. On the other hand, phenolic compounds which are not substrates for chloroperoxidase bind to the enzyme with a much different disposition, with the phenol group very distant from the iron and probably actually outside the active-site cavity.

Nonpeptidic inhibitors of human leukocyte elastase. 3. Design, synthesis, X-ray crystallographic analysis, and structure-activity relationships for a series of orally active 3-amino-6-phenylpyridin-2-one trifluoromethyl ketones.

Abstract: A series of nonpeptidic inhibitors of human leukocyte elastase (HLE) is reported. These trifluoromethyl ketone-based inhibitors contain a 3-amino-6-phenylpyridone group as a central template. The effect of varying the N-3 substituent in these inhibitors on in vitro potency, physical properties, and oral activity in a hamster based, HLE-induced lung damage model is described. The variety of substituents at this position that have little effect on in vitro potency supports the idea that this region of the molecule does not interact strongly with the enzyme. One exception to this generality is 13k, which is substituted with a (4-acetamidophenyl)sulfonyl group. This compound has a K(i) of 0.7 nM and is, in vitro, the most potent inhibitor in the series. In contrast, variation of the N-3 substituent was found to have a dramatic effect on activity after oral administration. Several analogs, including the parent amine, 7, formamide, 2u, benzyl sulfamide, 13e, and benzyl sulfonamide, 13f, show significant activity when administered at an oral dose of 2.5 mg/kg. Support for the modeling-based design concepts was obtained through in vitro SAR results and X-ray crystallographic analysis of the complex between 13d and porcine pancreatic elastase (PPE), a closely related enzyme.

Guanidine derivatives as inhibitors of na+/h+ exchange in cells

Abstract: Guanidine derivatives of formula (I), wherein Y is N or C-R1 (in which R1 is hydrogen, lower alkyl, hydroxy, protected hydroxy, etc.), R2 is hydrogen, aryl which may have one suitable substituent, aryloxy, etc., R3 is hydrogen, lower alkoxy, hydroxy, protected hydroxy, etc., Z is N or C-R4 (in which R4 is hydrogen, carboxy, protected carboxy, nitro, halogen, hydroxy(lower)alkyl, etc.), and W is N or C-R12 (in which R12 is hydrogen, lower alkoxy, nitro, hydroxy or protected hydroxy), and pharmaceutically acceptable salts thereof which are useful as a medicament.

Comparative Cumulene Substituent Effects: Ketenes, Allenes, Diazomethanes, Diazirines, and Cyclopropenes by ab Initio Molecular Orbital Calculations

Abstract: Ab initio calculations of the effect of substituents on the structures and energies of ketenes (1), diazomethanes (3), diazirines (4), allenes (5), and cyclopropenes (6) reveal that the isodesmic substituent stabilization energies of 1, 3, and 5 relative to alkenes are correlated with group electronegativities with slopes of -15.1, -10.6, and -1.8, respectively, at the HF/6-31G * +ZPVE/HF/6-31G * level, corresponding to a successive decrease in polar character of the cumulenes in this order. Isomerization energies of 3 to 4 show that the relative stabilities of substituted diazomethanes and diazirines are dominated by the stabilization of diazomethanes by electropositive substituents

Electrostatic vs Hyperconjugative Effects as Stereoinductive Factors in the Adamantane Ring System

Abstract: A series of 5-substituted (X) adamant-2-yl derivatives 1 (Y=O and CH 2 ) have been synthesized and their 13 C NMR spectra measured. The carbonyl and ethylenic 13 C substituent chemical shifts (SCS) are shown to be proportional to substituent field effects (σ F ). By use of the polar field susceptibility parameter (ρ F ) for the former shifts, polar field parameters (Δσ F values) have been calculated for a series of p-SC 6 H 4 substituents