Saponification Of Esters Research Articles

Kinetic resolution of esters of amino acids in t‐butanol containing 5% water catalyzed by a stable industrial alkaline protease

AbstractWe developed a procedure for the resolution of esters of amino acids in 95% t‐butanol, followed by saponification of the unreacted esters to afford both enantiomers with high yield and optical purity. The hydrolysis, catalyzed by alkaline protease, was conducted in a mixture of t‐butanol (95%) and water (5%) at 25°C, with a pH controlled at pH 8.5 by the addition of NaOH (2 M). The hydrolyzed L‐amino acid, which was insoluble under these conditions, precipitated during the course of hydrolysis. After separation of the precipitate, the pH of the filtrate was adjusted to 11.5 to saponify the unreacted ester. The D‐antipode precipitated at pH 6.2–6.5. Both optically pure antipodes were obtained with high enantiomeric excesses and yields by simple filtration. © 1994 Wiley‐Liss, Inc.

Solid-Liquid Phase Transfer Catalysis Without Solvent Coupled with Microwave Irradiation: A Quick and Efficient Method for Saponification of Esters

Abstract Hindered esters can be easily saponified in a few minutes using microwave activation under solid-liquid PTC conditions without solvent. A monomode microwave reactor (Maxidigest MX 350 Prolabo) is the most efficient. A non thermal effect of microwaves is evidenced by reference to classical heating.

Synthesis and antitumor activity of 10-propargyl-10-deazaaminopterin.

Successive alkylation of dimethyl homoterephthalate with propargyl bromide and 2,4-diamino-6-(bromomethyl)pteridine followed by ester saponification at room temperature afforded 2,4-diamino-4-deoxy-10-carboxy-10-propargyl-10-deazapteroic acid. The 10-COOH was readily decarboxylated by heating in DMSO at a temperature of only 120 degrees C to yield the diamino-10-propargyl-10-deazapteroic acid intermediate. Coupling with diethyl L-glutamate and ester hydrolysis gave the title compound. The 10-propargyl analogue was about 5 times more potent than MTX as an inhibitor of growth in L1210 cells, but was only one-third as potent as an inhibitor of DHFR from L1210. The analogue was transported inward very effectively in L1210 cells showing a 10-fold advantage over MTX. At a dose of 36 mg/kg the 10-propargyl compound caused shrinkage of the E0771 solid murine mammary tumor to only 1% of untreated controls.

Analysis of n-3 fatty acids in fish oils by high-performance liquid chromatography

A chromatographic method has been developed for the determination of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fish oil dietary supplements containing triglycerides rich in (n−3) polyunsaturated fatty acids (PUFAs). Following the ester saponification, free fatty acids were resolved by TLC into two fractions: i) a more mobile group of saturated and monounsaturated fatty acids and ii) a less mobile group containing PUFAs. The PUFA fraction was further analyzed by HPLC to determine the levels of EPA and DHA in the fish oil sample.

Derivatives of poly(pyrrole) with deconjugated carbonyl substituents in β-position

Abstract Four ω-(3-pyrrolyl)esters were investigated by cyclic voltammetry, electron microscoy and conductivity measurements. The corresponding poly(pyrrole) derivatives exhibit enhanced conductivities compared to poly(3-acylpyrrole)s, and their electrochemical behavior resembles that of poly(3-alkylpyrrole)s rather than the poly(3-acylpyrrole) derivatives. Ester saponification occurring during electropolymerization was examined by gas chromatography.

Catalytic Effect of Aluminium Oxide in Ester Saponification Reactions

Catalytic Effect of Aluminium Oxide in Ester Saponification Reactions

A new strategy for the solid-phase synthesis of 5′-thiolated oligodeoxynucleotides

Abstract A novel procedure is described for the introduction of a masked thiol function at the 5′-terminus of oligodeoxynucleotides. An acetyl-protected thiol linker phosphoramidite has been prepared which can be coupled efficiently to fully protected oligonucleotides using standard solid-phase techniques. Our strategy is elaborated for oligothymidylates and is further illustrated for oligodeoxynucleotides which are base-protected with the 2-(acetoxymethyl)benzoyl group. Rapid base-deprotection can be accomplished in methanolic potassium carbonate which also effects saponification of the thioacetyl ester. The resultant free thiol is reacted in situ with dithiodipyridine to afford pyridyldisulfide-derivatized oligodeoxynucleotides.

Catalytic Effect of Aluminium Oxide in Ester Saponification Reactions

Catalytic Effect of Aluminium Oxide in Ester Saponification Reactions

Kondensierte 1.2‐Dithiole, I. Synthese von Thiolutin und verwandten Verbindungen

Ring‐Fused 1,2‐Dithioles, I. — Synthesis of Thiolutine and Related CompoundsThe 1,2‐dithiolopyrrole 1 (thiolutine) has been obtained on two different routes. Firstly, by synthesis of the dithiolopyrrole 6a and introduction of the acetamino function into compound 6d by nitration followed by ester saponification and decarboxylation. 6d is also available from 9k by oxidative ring contraction which occurs with simultaneous dealkylation of the benzylamino group. Secondly, by synthesis of the dithiinopyrrole 15b and introduction of the acetamino function into compound 15g by Beckmann rearrangement followed by ring contraction.

Synthesis and antifolate properties of 5,10-ethano-5,10-dideazaaminopterin

2-Carbomethoxy-4-(p-carbomethoxyphenyl)cyclohexanone was prepared in a four-step process and thermally condensed with 2,4,6-triaminopyrimidine to afford methyl 2,4-diamino-4-deoxy-7-hydroxy-5,10-ethano-5,10-dideazapteroate+ ++. Reduction of the 7-oxo function with borane gave the 7,8-dihydro pterin which was subsequently oxidized to the fully aromatic pteroate ester with dicyanodichlorobenzoquinone. Saponification of the benzoate ester, coupling with diethyl glutamate and final ester hydrolysis afforded the title compound. This novel deazaaminopterin analogue was approximately as potent as methotrexate in vitro in terms of DHFR and L1210 cell growth inhibition. There are indications of diastereomeric differences in the enzyme inhibition measurements. A significant transport advantage over MTX for influx into L1210 cells was observed. The compound was active against the E 0771 murine mammary solid tumor, but further investigation with individual diastereomers is required to define the ED50.

Efficient Synthesis of Racemic and Enantiomerically Pure 1,2,3,4-Tetrahydroisoquinoline-3-carboxylic Acid and Esters

Racemic and optically pure 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids and esters were prepared, via base-catalyzed cyclization of 1,2-bis(halomethyl)benzenes 1a or b with diethyl 2-(acetylamino)malonate (2), subsequent decarboxylation and amide cleavage. The enantiomer resolution was achieved either by esterification with (-)-menthol followed by column chromatographic separation of the diastereomeric mixture or by diasteromeric salt separation of the benzylic ester with mandelic acid and base-catalyzed saponification of both esters

Factors Influencing the Accuracy of the National Reference System Total Cholesterol Reference Method

Previous comparisons between the Reference and Definitive Methods for measuring serum cholesterol have demonstrated a small but persistent positive bias in the Reference Method, averaging about +1.6%. Here we describe the results of further investigations designed to better characterize the nature of this bias. Analysis of a well-characterized model serum sample (SRM 909) suggests that more than half of the difference in cholesterol values determined by the two methods is the result of small contributions from cholesterol precursor sterols and phytosterols, which are also measured for the Reference Method. An additional significant contribution may be from cholesterol oxidation products, particularly 7-hydroxycholesterol isomers, which are active in the Liebermann-Burchard reaction. The 7-hydroxycholesterol in SRM 909, most of which appeared to be already present in the serum rather than formed during saponification, may account for as much as 20% of the observed difference between the methods. Contributions from other possible sources, including impurities in the cholesterol standard and incomplete saponification of cholesteryl esters, are very small. Because the observed bias is both quite small and consistent among samples, the cholesterol Reference Method continues to meet all of the requirements generally expected for a dependable and effective Reference Method.

Triterpenoids form species of Abies. XI. Ready fragmentation in the side chains of the molecules of triterpene ?,?-unsaturated ?-keto acids

The structure of new trinortriterpene netural compounds formed as the result of the fragmentation of the side chains during the saponification of methyl esters of α,β-unsaturated γ-keto acids under the action of alcoholic alkali have been established by physicochemical methods.

Synthesis and antifolate properties of 9-alkyl-10-deazaminopterins

Reformatski condensation of benzyl 2-bromopropionate with 4-carbomethoxybenzaldehyde, followed by dehydration afforded benzyl 2-methyl-p-carbomethoxycinnamate (4a). Hydrogenation over a Pd catalyst gave the hydrocinnamic acid 5a. Conversion to the chloromethyl (6a) and azidomethyl ketone (7a) was followed by hydrogenation to the aminomethyl ketone (8a). Direct N-alkylation by 2,4-diamino-5-nitro-6-chloropyrimidine followed by reductive ring closure in Zn-HOAc and subsequent saponification of the benzoate ester yielded 4-amino-4-deoxy-9-methyl-10-deazapteroic acid (11a). Coupling with diethyl L-glutamate and saponification afforded 9-methyl-10-deazaminopterin (13a). The 9-ethyl analogue (13b) was similarly prepared from benzyl 2-bromobutyrate. The 9-methyl analogue (13a) was 21 times more potent than MTX as an inhibitor of cell growth in L1210 cells. The reason for this enhanced cytotoxicity in L1210 is unclear, since enzyme inhibition and transport parameters were similar to those of MTX. In human Manca leukemia cells growth inhibition was not dramatic and paralleled MTX.

Studies related to penicillins. Part 28. β-Elimination reactions of sulphones derived from penicillins leading to cis-3-acylamino-4-oxoazetidine-2-sulphinic acids

The reactions of the 3-acetyl and 3-formyl derivatives of (3S,5R,6R)-2,2-dimethyl-6-phenoxyacetamidopenam 1,1-dioxide, i.e. compounds (5e,f), and of p-nitrophenyl (3S,5R,6R)benzylpenicillinate 1,1-dioxide (1f) with 1,5-diazabicyclo[5.3.0]non-5-ene (DBN) followed by iodomethane have been studied. In the case of penam dioxide (5e), epimerisation at position 6 competes with the β-elimination at position 3 and a mixture of the trans- and cis-azetidinones (11a) and (12a) is isolated. No epimerisation is observed with compounds (5f) and (1f), which react to give the corresponding cis-azetidinones (12b,c). It is possible to avoid the epimerisation of the penam dioxide (5e), and to isolate the cis-azetidinesulphinate salt (13), by using potassium t-butoxide in place of DBN. The cis-azetidinesulphinic acid (8c) is also isolable from the reaction of the penicillinate dioxide (1f) with DBN followed by acidic work-up. It undergoes O-methylation of the sulphinic acid group in the presence of diazomethane to give the methyl sulphinate (19), as a mixture of diastereoisomers. Saponification of the p-nitrophenyl ester of the cis-azetidinesulphinic acid (8c) is effected by sodium hydroxide to give the disodium salt (18b), which undergoes methylation in the presence of iodomethane to afford the dimethyl derivative (12d).

Pyryliumverbindungen. 36. Substituierte Benzoesäureester aus 2,4,6‐Triaryl‐pyryliumsalzen und α‐Ketocarbonsäureestern

Pyrylium Compounds. 36. Substituted Benzoic Acid Esters from 2,4,6‐Triarylpyrylium Salts and α‐Ketocarboxylic Acid Esters2,4,6‐Triarylpyrylium salts 1 react with α‐ketocarboxylic acid esters 2 in the presence of two equivalents of an appropriate condensing agent (e.g. dialkylamine salts of weak acids, triethylamine/acetic acid, or sodium acetate) to give 2‐aroyl‐3,5‐diarylbenzoic acid esters 3. However, using only one equivalent of the condensing agent, the formation of 3,5‐diarylbenzoic acid esters 5 predominates. Alkaline saponification of the new esters 3 and 5 yields the corresponding substituted benzoic acids 4 and 6, respectively. – I.r., u.v., n.m.r. and mass spectroscopic data of the novel products 3–6 are reported.

4‐Methylumbelliferyl 5‐Acetamido‐3,4,5‐trideoxy‐α‐D‐manno‐2‐nonulopyranosidonic Acid: Synthesis and Resistance to Bacterial Sialidases

AbstractThe synthesis of 4‐methylumbelliferyl α‐D‐glycoside 13 of N‐acetyl‐4‐deoxyneuraminic acid and its behaviour towards bacterial sialidases is described. N‐Acetyl‐4‐deoxyneuraminic acid (1) was transformed into its methyl ester 2 and then acetylated to give the anomeric pentaacetates 3 and 4 of methyl 4‐deoxyneuraminate and the enolacetate 5 (Scheme). A mixture 3/4 was treated with HCl/AcCl to give the glycosyl chloride, which was directly converted into the 4‐methylumbelliferyl α‐D‐glycoside 9 of methyl 7‐O,8‐O,9‐O,N‐tetraacetylneuraminate and into the 2,3‐dehydrosialic acid 11. The ketoside 9 was de‐O‐acetylated to 12 with NaOMe in MeOH. Saponification (NaOH) of the methyl ester 12 followed by acidification gave the free 13, which was also converted into the sodium salt 14 by passage through Dowex 50 (Na+). The 4‐deoxy α‐D‐glycoside 13 is not hydrolyzed at significant rates by Vibrio cholerae and Arthrobacter ureafaciens sialidase. Neither the free N‐acetyl‐4‐deoxyneuraminic acid (1), nor the α‐D‐glycoside 13 inhibit the activity of these sialidases.

ChemInform Abstract: Quinazoline Antifolates Inhibiting Thymidylate Synthase: Variation of the Amino Acid.

AbstractDie neuen Ana1oga(IIIa)‐(IIId) sowie (VIIIa)‐(VIIIc) der N‐Propargy1‐ 5,8‐didesazafolsäure (VIIId) werden nach den im Formelschema angegebenen Methoden synthetisiert und als Inhibitoren der L 1210‐Thymidylat‐Synthase (TS) sowie als Hemmstoffe des Wachstums von L 1210‐Zellen geprüft.

Quinazoline antifolates inhibiting thymidylate synthase: variation of the amino acid.

Five new analogues (1c-g) of the antifolate N10-propargyl-5,8-dideazafolic acid (1a) are described in which the benzoyl-L-glutamate moiety was replaced by benzoic acid (desglutamyl-N10-propargyl-5,8-dideazafolic acid), benzoyl-L-aspartate, 4-phenylbutyrate, benzoylglycine, and benzoyl-L-alanine. The esters of the appropriate 4-aminophenyl (benzoyl) starting materials were sequentially alkylated upon nitrogen, first with a propargyl halide and then with 2-amino-6-(bromomethyl)-4-hydroxyquinazoline hydrobromide. Saponification of the antifolate esters so produced gave the desired analogues. The new derivatives (1c-g) and also the known diethyl ester of 1a (1b) were tested for their inhibition of purified L1210 thymidylate synthase (TS) and for their inhibition of the growth of L1210 cells in culture. The TS inhibition of the analogues 1b-g was estimated by calculating the inverse relative potency, defined as the ratio IC50(compound)/IC50(1a). The results obtained were as follows: greater than 62, 84, 9, 333, 21, and 5, respectively. All were thus less inhibitory than 1a. None of the compounds improved upon 1a in inhibiting the growth of L1210 cells in culture.

The chemical and enzymatic oxidation of hematohemin IX. Identification of hematobiliverdin IX alpha as the sole product of the enzymatic oxidation.

Oxidative cleavage of hematohemin IX in pyridine solution in the presence of ascorbic acid (coupled oxidation), followed by esterification of the products with boron trifluoride/methanol produced the four possible hematobiliverdin dimethyl esters in 11.1% overall yield. Transetherifications took place simultaneously with the esterification reaction and resulted in the formation of the dimethyl ester of hematobiliverdin IX gamma 8a,13a-dimethyl ether (1.8%), the dimethyl ester of hematobiliverdin IX beta 13a,18a-dimethyl ether (1.9%), the dimethyl ester of hematobiliverdin IX delta 8a-monomethyl ether (1.4%), and the dimethyl ester of hematobiliverdin IX alpha 18a-monomethyl ether (0.4%). The latter was the sole product obtained after the enzymatic oxidation of hematohemin with heme oxygenase, after esterification of the reaction product with boron trifluoride/methanol. When the esterification step was omitted hematobiliverdin IX alpha was obtained from the enzymatic oxidation. The structures of the hematobiliverdin derivatives were secured by their NMR and mass spectra data. Saponification of the dimethyl esters afforded the hematobiliverdin methyl ethers, which were excellent substrates of biliverdin reductase and were readily reduced to the corresponding bilirubins. Hematobiliverdin IX alpha was also a good substrate of biliverdin reductase. It is concluded that the enzymatic oxidation of hematohemin IX by heme oxygenase is alpha-selective, while biliverdin reductase shows no selectivity in the reduction of the four hematobiliverdin isomers.