Search

D- and L-5-aminohex-2-enedioic acid (AHED) and the DL-2-bromo derivative, which are conformationally restricted analogues of the excitatory amino acid antagonist D-alpha-aminoadipic acid (D alpha AA), were tested microelectrophoretically on cat spinal neurones. D-AHED reduced the excitatory action of N-methyl-D-aspartate (NMDA) to a greater extent than that of L-glutamate and the potency of this action was a half to a third that of D alpha AA. The DL-2-bromo derivative excited neurons, an effect greater than that of L-glutamate and not blocked by either D alpha AA or L-glutamic acid diethyl ester.

Systemic injection of GDEE (glutamate diethyl ester), an antagonist of glutamate and aspartate receptors, induces stretching and yawning in rats. This was not accompanied by excessive grooming. Coupled with previous work these findings give evidence that a glutamatergic mechanism is involved in stretching and yawning.

The synthesis of the above-mentioned compounds, starting from the diethyl ester of 2,5-pyrrolidine dicarboxylic acid, is reported. The cis and trans isomers od the 2-phenylsubstituted acid were separated, and the trans form was resolved into the two chiral forms. Some amides were also prepared from these acids. The thio analogs (XIII) and (XVI) and the partially reduced derivatives (XIV) were synthesized. Some amides (VI) showed an interesting anti-anxiety effect in pharmacological models.

The synthesis and antibacterial activities of 4-hydroxyquinoline-3-carboxylic acid and 1,4-dihydro-1-ethyl-4-oxoquinoline-3-carboxylic acid containing a pyrrole or 2,5-dimethylpyrrole group at 6 position are reported. Reaction of 1-(4-aminophenyl)pyrrole or 2,5-dimethyl-1-(4-aminophenyl)-pyrrole with ethoxymethylenemalonate diethyl ester (EMME) afforded the related pyrroleanilinomethylenemalonates, which were subjected to thermal cyclization to give the required quinoline derivatives. These compounds on ethylation furnished at last the quinolonecarboxylic analogs of nalidixic acid.

The treatment of 4-(2-aminophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinecarboxylic acid diethyl ester (III) with refluxing toluene or pyridine afforded 1,2,3,6-tetrahydro-2,4-dimethyl-2,6-methano-1,3-benzodiazocine-5,11-dicarboxylic acid diethyl ester (IV) as the major product. In addition, the following minor products were isolated: 2-methyl-3-quinolinecarboxylic acid ethyl ester (V), 3-(2-aminophenyl)-5-methyl-6-azabicyclo[3,3,1]-hept-1-ene-2,4-dicarboxylic acid diethyl ester (VI), and 5,6-dihydro-2,4-dimethyl-5-oxobenzo[c][2,7]naphthyridine-1-carboxylic acid ethyl ester (VII). In contrast, acidic conditions caused the conversion of III into V in a 95% yield. The formation of the latter appears to involve IV as an intermediate, since IV degraded rapidly in acid to give V in a quantitative yield.

Addition of 1,8-diaminonaphthalene1 to dimethylacetylene dicarboxylate (DMAD) leads to the perimidine4a and the naphthodiazepine3a. A similar reaction with the diethyl ester (DEAD) gave rise to3b and4b. The latter product has been incorrectly formulated as naphthodiazepine2b in the literature. 1,8-Dihydroxynaphthalene8 and DMAD gives rise to the naphthodioxane9, which is hydrolysed to the diacid11. 8-Hydroxy-1,2,3,4-tetrahydroquinoline (14) and acetylenic esters form pyridobenzoxazines15, which exist as equilibrium mixture of15 and16 in solution. The ethyl ester is hydrogenated to the dihydroderivative18b.1H and more particularly13C NMR spectra are used to assign structures to various products.

Squaric acid diethylester and squaric acid dibutylester have been used in contact sensitization therapy of alopecia areata. This study investigated the application of these esters or squaric acid alone to hairless mouse and human skin in vitro to determine squaric acid flux from the various preparations. Measurable amounts of squaric acid were delivered through skin by squaric acid itself, but flux was lower than for that delivered by the two esters. These results support the proposal by Noster that the esters combine with a protein to form an antigen while squaric acid can not and that this explains why the esters are active in contact sensitization and the acid is not. We suggest that the results of previous studies showing that the diethyl ester of squaric acid was a less effective sensitizer than the dibutyl ester may have been due to decomposition of the ethyl ester to squaric acid.

The diethyl ester of bis[6-(2-phenylcinchoninic acid)] sulfone, the corresponding sulfide and disulfide derivatives, and the disulfide acid were prepared. The results of chemotherapeutic testing for antimalarial activity are reported.

A synthesis of the phosphonic acid analogues of L-α- and D-α-glycerophosphoric acid, viz. L- and D-dihydroxypropylphosphonic acid, is described. The L-dihydroxypropylphosphonic acid was obtained by treating acetone α-iodo-L-propylene glycol with triethyl phosphite at 120–125° for 24 h, hydrolyzing the condensation product acetone L-dihydroxypropylphosphonic acid diethyl ester with 2 N sulfuric acid at 100° for 48 h, and isolating the L-dihydroxypropylphosphonic acid as barium salt. The D-dihydroxypropylphosphonic acid was prepared in the same manner from acetone α-iodo-D-propylene glycol. The barium salts are readily soluble in cold water, much less soluble in hot water, and insoluble in the more common organic solvents. Dihydroxypropylphosphonic acid and α-glycerophosphoric acid can be distinguished from each other by their different behaviors towards hot mineral acids, and by the infrared spectra, n.m.r. spectra, and optical rotations of their barium salts.

When 2, 5-dianitino-3, 6-dihydroterephthalic acid diethyl ester (1) was heated in toluene, reaction proceeded according to eq. [1]._??_-N-H-_??_-O=C-EtO-N-H-_??_-C=O-OEt→step1 _??_-O=C-N-H-_??_-C=O-OEt→step2 _??_-O=C-N-H _??_-N-H-O=C-_??_… [1] (1) (2) (3) (1)(2)(3)The activation energy of step-1 was 42.1 kcal/mol and that of step-2 was 86.0 kcal/mol. The half cyclized product (2) can be synthesized with high purity when the reaction temperature is controlled at around 230°C.The reaction occurs only in nonpolar solvents. The presence of alcohol in the solvent strongly inhibited the reaction and gave ester-exchanged products. Since the reaction is not catalized by acids or bases and is not affected by the substituents on the aromatic ring of (1), ionic transition state is probably not involved in the rate determining step.Large difference in activation energy between step-1 and step-2 can be explained by the transition state of highly strained bond angle in step-2; the increase of rigidity of cyclohexadiene ring in (2) as a result of half cyclization requires high energy to form the transition state.

The title compound was synthesized via its diethyl ester from 1-pyrroline trimer and diethyl phosphite. The 3-mercaptopropanoyl derivative inhibited angiotensin converting enzyme with I 50 = 1.7 μM.

Hydantoin-5-malonic acid diethyl ester was synthesized by reduction of parabanic acid (oxalyl urea) to 5-hydroxy-hydantoin, conversion to 5-chlorohydantoin and condensation with malonic ester. Alkaline hydrolysis gave d,l -β-carboxyaspartic acid.

The preparation of 6,6′-[(2-hydroxy-1,3-propanediyl)]bis(oxy)]bis(3-hydroxy)]-2-benzofurancarboxylic acid) diethyl ester trisodium salt trihydrate (6), a compound structurally related to disodium cromoglycate (DSCG), is described.

Treatment of compound N,N-(dithiobis(3-chloro-2,1-phenylene)dicarbonylbis (N-cyclopentylglycine)diethyl ester (3) with methanolic sodium hydroxide does not produce the expected hydrolysis product N,N-(dithiobis-(3-chloro-2,1-phenylene)dicarbonylbis (N-cylcopentylglycine) (4) but yields a mixture of compounds 8-chloro-3-cyclopentyl-3,4-dihydro-4-oxo-2H-1,3-benzothiazine-2-carboxylic acid (6) and N-(3-chloro-2-mercaptobenzoyl)-N-cyclopentylglycine (7). This unexpected observation has the potential of a new heterocyclic synthesis method for the 4-oxo-2H-1,3-benzothiazine class of compounds.

1. The dipole moments of the dichlorides and diethyl esters of the styryl- and p-chlorostyrylphosphonic acids were determined. In the diethyl ester of p-chlorostyrylphosphonic acid the diethoxyphosphono group takes a substantial part in the common conjugation chain. 2. The diethoxyphosphono group and the phenyl ring in the diethyl esters of the p-halo- and p-nitro-α-cyanostyrylphosphonic acids are found in the trans-position.

1. A study was made of the reaction of p-dimethylaminobenzyldiethylamine, p-dimethyiaminobenzyl ethyl ether, p-methoxybenzyl ethyl ether and p-methoxybenzyl acetate with triethyl phosphite. The compounds, containing the dimethylamino group in the p-position, react with triethyl phosphite in the presence of acetic acid to give the diethyl ester of p-dimethylaminobenzylphosphonic acid. The other analogs do not react with triethyl phosphite. 2. The methiodides of p-dimethylaminobenzyldiethylamine and diethylbenzylamine react with triethyl phosphite to give respectively the p-dimethylaminobenzyl- and benzylphosphonates.

1. The EPR spectra of the anion radicals ofα,α′-azoisobutyrodinitrile and the diethyl ester of azoacetic acid were studied. 2. In the formula describing the interaction of the unpaired electron with the nitrogen nucleus, the value of the polarization parameter for the 2s-electrons of the nitrogen atoms, due to the spin density on the nitrogen atom, possesses a value of 9.8 Oe for the sp2-hybridized carbon atom next to the nitrogen, and 5.3 Oe for the sp3-state.

Durch Umsetzung von Cyclohexanon-2-carbonsaureathylester bzw. 1,4-Cyclohexandion-2,5-dicarbonsaurediathylester mit mehrwertigen Phenolen konnten Verbindungen der 1,2,3,4-Tetrahydroxanthon-Reihe und der 3,4-Cyclohexenylcumarin-Reihe erhalten werden, die antioxidative Eigenschaften besitzen. Durch Einfuhrung einer Carboxylgruppe konnte neben der Fettloslichkeit eine gewisse wasserlosliche Eigenschaft dieser Verbindungen erreicht werden. Die Autoxidationsversuche durch Begasung mit Luftsauerstoff wurden vorwiegend an ungesattigten Fettsauren und Fettsaureestern bei verschiedenen Temperaturen durchgefuhrt. Bei den untersuchten Verbindungen zeigte es sich, das die o-Dihydroxyverbindungen bei niedrigen Temperaturen eine langer anhaltende Inhibitorwirkung besitzen, wahrend die p-Dihydroxyverbindungen eine maximale inhibierende Wirkung gegenuber Luftsauerstoff erst bei hoheren Temperaturen aufweisen. New Antioxidants and Their Properties Compounds of the 1,2,3,4-tetrahydroxanthone series and the 3,4-cyclohexenyl cumarine series, all having antioxidative properties, were prepared by reacting the ethyl ester of cyclohexanone-2-carboxylic acid and the diethyl ester of 1,4-cyclohexanedione-2,5-dicarboxylic acid with polyvalent phenols. The fat-solubility and a certain watersolubility of these compounds were achieved by the introduction of a carboxyl group. Autoxidation tests using atmospheric oxygen were carried out mainly on unsaturated fatty acids and their esters at various temperatures. Among the substances studied the o-dihydroxy compounds showed inhibitor action for long periods at low temperatures, whereas the p-dihydroxy compounds had a maximum inhibiting action towards atmospheric oxygen only at high temperatures.

A method for the synthesis of isoprenoid acids is proposed, based on the reaction of isoprenoid ketones with the diethyl ester of carbethoxymethylphosphonic acid.

The dichloride of β-ethoxyvinyl-, β-isooctyloxyvinyl-, and 2-chloro-3-methylbut-3-enylphosphonous acids have been synthesized and characterized for the first time. The diethyl ester of β-ethoxyvinylphosphonous acid has been-obtained from the dichloride of β-ethoxyvinylphosphonous acid.

Reaction of trans-2,3-dichloro-1,4-dioxan with dimethyl (+)-tartrate yields dimethyl (–)-1,4,5,8-tetraoxadecalin-2,3-dicarboxylate in which the ring fusion is cis. The diethyl ester has been obtained similarly, and the dihydrazide and a monoamide monoethyl ester have been prepared.The assignment of the ring-fusion as cis in these compounds is made from n.m.r. studies at 100 MHz.

3H-Pyrrolizine reacts with dimethyl ordiethylacetylenedicarboxylate to give the 3-[alkoxycarbonyl(alkoxycarbonyl-methyl)methylene]-3H-pyrrolizines (5) and (8). 1-Methyl-3H-pyrrolizine and 6,7-dimethylpyrrolizine give the similar compounds (6) and (7) with the dimethyl ester; with the diethyl ester 1-methyl-3H-pyrrolizine gives a 3H-pyrrolizin-5-ylmaleate (13) shown to be an intermediate in the production of the expected compound (10). A mechanism for the reaction has been proposed, and tested by deuterium-labelling experiments. 3-Diphenyl-methylene-3H-pyrrolizine undergoes cycloaddition with dimethyl acetylenedicarboxylate to give a dihydrocycl-[3,2,2]azine (dimethyl 5,6-dihydro-5,5-diphenylpyrrolo[2,1,-cd]indolizine-6,7-dicarboxylate)(14).

The synthesis of porphins by cyclisation of the dihydrobromides of 1-bromo-19-methyl-1,19-dideoxybiladienes-ac in boiling o-dichlorobenzene has been extended to the preparation of certain rhodoporphyrins and related compounds. Dimethyl sulphoxide–pyridine can be used as an alternative solvent and the cyclisation then proceeds at room temperature. The effect on the yield of porphin of the proximity of the nuclear ester group to the point of cyclisation has been determined and the results have been used in a synthesis of rhodoporphyrin XV diethyl ester, previously obtained only in a yield of 0·1%, and now obtained in 31% yield. Pyrroporphyrin XV methyl ester, containing an unsubstituted β-position, has also been synthesised (27%).