Carboxy Function Research Articles

Recognition sites incorporating both pyridinyl and carboxy functionalities prepared by molecular imprinting

Noncovalent molecular imprinting using simultaneously two chemically distinct functional monomers, namely the weedy basic 2-vinylpyridine and the acidic and hydrogen bonding methacrylic acid, war demonstrated in ethylene glyool dimethacrylate bared copolymers. Terpolymerizations of this type were shown to be particularly useful for the preparation of imprints against carboxylic acids, which additionally contained a complex array of other chemical functionalities. Such imprinted polymers demonstrated improved recognition capabilities as compared with polymers which were prepared using only one of the functional monomers

Enzymatic Protecting Group Techniques in bioorganic synthesis

The development and the application of enzyme-catalyzed transformations for the introduction and/or removal of protecting groups for hydroxyl-, amino-, mercapto- and carboxy functions is discussed. The various examples highlight the advantageous application of enzymes in comparison to classical chemical techniques in the chemistry of peptides, carbohydrates, alkaloids and steroids. Thus, the biocatalysts not only complement the arsenal of classical chemical methods, but offer viable and interesting alternatives to them.

Use of the chlorophyll derivative, purpurin-18, for syntheses of sensitizers for use in photodynamic therapy

Reactions of purpurin-18 methyl ester 6 with various nucleophiles have been investigated as a means for synthesis of sensitizers for use in photodynamic therapy of tumours. Use of butylamine as the nucleophile resulted in ring-opening of the purpurin-18 anhydride ring to give a monoamide-γ-carboxylic acid 8, the purpurin-imide 11, and the di-amide-γ-carboxylic acid 12. When lysine or its esters were used as nucleophile, then lysylamide-γ-carboxylic acids 18, 20 and 23 were obtained, along with the purpurin lysyl-imides 21 and 22. Esterification and hydrolysis of the various carboxy functions were investigated as a means for obtaining stable water-soluble sensitizers. Similar reactions between ornithine and purpurin-18 methyl ester gave the corresponding ornithyl-chlorin-p6 derivatives (e.g.31). The lysyl-chlorin-p618 was shown (in separate work) to be a highly effective tumour sensitizer.

Deoxyiminoalditols from Aldonolactones; I. Preparation of 1,4-Dideoxy-1,4-iminohexitols with D- and L-Allo and D- and L-Talo Configuration: Potential Glycosidase Inhibitors

1,4-Dideoxy-1,4-iminohexitols were prepared by a convenient two-step reaction from 2,6-dibromo-2,6-dideoxyhexono-1,4-lactones by treatment with aqueous ammonia and subsequent reduction of the carboxy function with sodium borohydride. By interchange of the reactions, the dibromolactones were reduced to 2,6-dibromohexitols, which by reaction with aqueous ammonia yielded the same imino compounds. Thus, from 2,6-dibromo-2,6-dideoxy-D-mannono- (1) and -D-glucono-1,4-lactone (9) the 1,4-dideoxy-1,4-imino-L-allitol (6) and -D-talitol (14) were prepared, respectively. These two compounds were also obtained from 2,6-di-bromo-2,6-dideoxy-D-mannitol (5) and -D-glucitol (13), respectively, by reaction with aqueous ammonia. The enantiomeric 1,4-dideoxy-1,4-imino-D-allitol (18) and -L-talitol (22) were prepared similarly from the new 2,6-dibromo-2,6-dideoxy-L-mannono- (16) and -L-glucono-1,4-lactone (20), via the dibromo-L-hexitols 17 and 21, respectively. The ring closure of the dibromo compounds with ammonia has been shown to proceed via epoxides.

Deoxyiminoalditols from Aldonolactones; II. Preparation of 1,4-Dideoxy-1,4-iminohexitols with D- and L-Galacto and D- and L-Ido Configuration: Potential Glycosidase Inhibitors

1,4-Dideoxy-1,4-iminohexitols were prepared by a convenient two-step reaction from 2,6-dibromo-2,6-dideoxyhexono-1,4-lactones by treatment with aqueous ammonia and subsequent reduction of the carboxy function with sodium borohydride. By interchange of the reactions, the dibromolactones were reduced to 2,6-dibromohexitols, which by reaction with aqueous ammonia yielded the same imino compounds. Thus, from 2,6-dibromo-2,6-dideoxy-D-mannono- (1) and -D-glucono-1,4-lactone (9) the 1,4-dideoxy-1,4-imino-L-allitol (6) and -D-talitol (14) were prepared, respectirely. These two compounds were also obtained from 2,6-dibromo-2,6-dideoxy-D-mannitol(5) and D-glucitol(13) respectively, by reaction with aqueous ammonia. The enantiomeric 1,4-dideoxy-1,4-imino-D-allitol(18) and -L-talitol(22) were prepared similarly from the new 2,6-dibromo-2,6-dideoxy-L-mannono-(16) and L-glucono-1,4-lactone(20) via the dibromo-L-hexitols 17 and 21, respectively. The ring closure of the dibromo compounds with ammonia has been shown to proceed via epoxides

Synthesis of Muropeptide Conjugates of 2,3-Dideoxy-β-D-manno-2-octulosonic Acid

Although an inhibitor of the bacterial lipopolysaccharide biosynthesis, the title compound 2-deoxy-β-KDO (1) cannot pass through the bacterial membrane. The coupling of the carboxy function with peptidic carriers creates conjugates (prodrugs) like 2, which can be actively transported into the cell. Their stability in vivo can be modulated by modifying the potential cleavage sites.

Studies on the reactivity of acyl glucuronides—I: Phenolic glucuronidation of isomers of diflunisal acyl glucuronide in the rat

Diflunisal (DF) is metabolized primarily to its acyl glucuronide (DAG), phenolic glucuronide (DPG) and sulphate (DS) conjugates. Whereas DPG and DS are stable at physiological pH, DAG is unstable, undergoing hydrolysis (regeneration of DF) and rearrangement (intramolecular acyl migration to the 2-, 3- and 4- O-acyl-positional isomers). We have compared the in vivo disposition of DAG with that of an equimolar mixture of its three isomers after i.v. administration at 10 mg DF equivalents/kg to conscious, bile-exteriorized rats. After dosing with DAG, excretion in urine and bile (46% as DAG), hydrolysis (as assessed by recovery of 9% DPG and 8% DS resulting from reconjugation of liberated DF) and rearrangement (17% recovery as isomers of DAG) were important pathways. Highly polar metabolites excreted almost exclusively in bile and accounting for 13% of the dose were identified as an approximate 4:1 mixture of the 2- and 3- O-isomers of DAG which had been glucuronidated at the phenolic function of the salicylate ring i.e. “diglucuronides” of DF. Evidence for trace quantities only of the phenolic glucuronides of the 4- O-isomer of DAG, and of DAG itself, was found. After dosing rats with an equimolar mixture of the isomers, 52% was recovered (as the isomers) in urine and bile in 6 hr. Hydrolysis was less important — <3% (total) of the dose was recovered as DPG and DS. The phenolic glucuronides of the 2- and 3- O-isomers (ratio ca. 3:7) accounted for 37%. Evidence for appreciable formation of the phenolic glucuronide of the 4- O-isomer was not found. In one rat dosed with DPG, there was no evidence for further glucuronidation of the salicylate ring at its carboxy function. The data suggest that the 2- and 3- O-isomers of DAG, but not the 4- O-isomer, DAG itself or DPG, are good substrates for further glucuronidation.

Synthesis of carbon‐11 labelled calcium channel antagonists

AbstractA useful synthetic approach to carbon‐11 labelled 1,4‐dihydropyridines is described. Carbon‐11 labelled calcium channel antagonists 11C‐Nifedipine, 11C‐Nisoldipine, 11C‐Nitrendipine and 11C‐CF3‐Nifedipine were synthesized by a modified Hantzsch method using protected carboxy functions. Deprotection of the carboxylic acids by alkaline hydrolysis followed by conversion into the corresponding potassium salts and subsequent methylation with 11CH3I produced the labelled compounds in very good chemical and radiochemical yields (94%).

Reactivity Parameters of the Metal Assisted 1,2-Cleavage of Penicillins

A straigtforward and smooth conversion of penicillins into 1,2-secopenicillanates is described. The thiazolidine ring opening is brought about by the co-operative effect of strong non-nucleophilic bases and thiophilic heavy metal salts. The nature of the latter and the polarity of the solvent profoundly affect the reaction rate.Best general conditions can be drawn for the conversion of numerous 6-substituted penicillanates with various protecting groups on the carboxy function.

Prodrugs of peptides: III. 5-Oxazolidinones as bioreversible derivatives for the α-amido carboxy moiety in peptides

The hydrolysis kinetics of six N-acyl 5-oxazolidinones derived from various N-benzyloxycarbonyl amino acids and aldehydes (formaldehyde, acetaldehyde and benzaldehyde) was studied to assess their suitability as prodrug forms for the α-amido carboxy moiety occurring in peptides. The degradation of the compounds was shown to take place by hydrolytic opening of the lactone ring with the formation of an N-hydroxyalkyl intermediate which subsequently decomposed to the parent N-acylated amino acid and aldehyde. For oxazolidinones derived from formaldehyde and acetaldehyde the latter reaction was rate-limiting whereas for derivatives of benzaldehyde the hydrolysis of the lactone ring was the slowest step at neutral pH. The lactone hydrolysis was catalyzed by human plasma enzymes and influenced by substituents in the 2- and 4-positions. It is suggested that 5-oxazolidinone formation may become a useful approach to bioreversible derivatization of peptides containing an α-amido carboxy function in an effort to protect peptide bonds against enzymatic cleavage and to improve absorption characteristics through increased hpophilicity. The potential utility of the N-hydroxyalkyl derivatives formed upon hydrolysis of the oxazolidinones as useful prodrug forms is also discussed.

Synthesis and Properties of Nα‐Di‐tert‐Butoxycarbonyl and Nα‐Benzyloxycarbonyl tert‐Butoxycarbonyl Amino Acids

The N-protected amino acids 1 and 2 should find universal application; they are now accessible in good to very good yields. The allyl group has proven to be the best protecting group for the carboxy function. The preparative use of 1 and 2 has been demonstrated by the synthesis of some dipeptides related to Leu-enkephalin.

The hydrolytic reactivity of homoprostacyclin: implications for the physiological control of bleeding

Rates of hydrolysis of the vinyl ether group of homoprostacyclin (2), which differs from prostacyclin only in that it has four instead of three carbon atoms in the chain joining this group to a carboxy function, were measured in H2O solution over the pH range 1–9 and in D2O solution in D2PO4––DPO42– buffers. The rate profile so obtained shows that homoprostacyclin is eight times more reactive in its carboxylate than in its carboxylic acid form, and an isotope effect on the accelerated reaction indicates that this rate increase is the result of intramolecular catalysis by the carboxylic acid group. This eight-fold acceleration is significantly less than the 100-fold increase produced by intramolecular catalysis in the case of prostacyclin itself, and that suggests that natural evolution has given prostacyclin the correct lifetime it needs to be effective in the physiological mechanism for the control of bleeding by adjusting the length of the carbon chain joining its vinyl ether and carboxy groups.

Membrane formation and characterization of semi-permeable magnetic polyhexamethyleneterephthalamide microcapsules containing polyethyleneimine (PEI) for trapping carcinogens.

The membrane characteristics were studied of semi-permeable magnetic polyhexamethyleneterephthalamide microcapsules containing polyethyleneimine (PEI) in order to optimize their use for trapping carcinogens in vivo. The microcapsules were prepared by interfacial polymerization techniques from an aqueous mixture of hexamethylenediamine, PEI and ferrofluid EMG 705 dispersed in an organic phase containing terephthaloyl chloride and trimesoyl chloride. The resulting microcapsule membranes had a complex structure consisting of a polyamide component (70-84 per cent by weight) with chain-terminating carboxy functions and the remainder were PEI incorporated throughout the membrane having residual amine functions. Substantial variation in preparative conditions had little effect upon membrane incorporation of PEI which cross-linked the polyamide chains. However, both TEM and SEM data indicated structural differences when lower concentrations of hexamethylenediamine were used, there being a more uniform formation to give a distinct outer membrane layer (18-45 nm) visible on cross-section and appearing as a smooth outer surface. Magnetite particles appeared to be present throughout the membrane. During membrane formation, no PEI was present in the organic phase, indicating that the microcapsule membrane had formed inwards contrary to the membranes formation reported previously in other systems. The inward transfer of reactive acid chlorides into the aqueous phase resulted in a core of modified PEI. Microcapsule binding of probe substances [14C]N-methyl-N-nitrosourea and eosin varied with the microcapsule preparative conditions used, and appeared to be critically dependent upon the membrane characteristics, especially the incorporation of PEI into the membrane. Characterization of membrane formation and properties allows the optimization of microcapsule binding properties.

Chromium(II) reduction of trichloromethyl carbinols and their corresponding ethers: one-step synthesis of Z-vinyl chlorides

Secondary trichloromethyl carbinols and their corresponding ethers can be reduced by chemically or electrochemically generated chromium(II) chloride to form Z-monochlorovinyl compounds in one step. In the presence of a carboxy function in the α-position an E-double bond is formed. Tertiary carbinols favour the formation of dichlorovinyl compounds and rearranged carbonyl compounds. Product ratios can be altered drastically by a change in the reaction conditions; this sheds light on the reaction mechanism.

ChemInform Abstract: SYNTHESIS OF THE GLYCOPEPTIDE PARTIAL SEQUENCE A80‐A84 OF HUMAN FIBROBLAST INTERFERON

AbstractDas Glykopentapeptid (IVc), das die Teilsequenz A80‐A84 von menschlichem Fibroblasten‐Interferon darstellt, wird ausgehend vom bekannten vollgeschützten N4‐glykosylierten Asparagin‐allylester (Ia) wie im Formelschema angegeben synthetisiert.

Synthesis of the Glycopeptide Partial Sequence A80–A84 of Human Fibroblast Interferon

AbstractThe glycopentapeptide H‐(GlcNAcβ1‐)Asn‐Glu‐Thr‐Ile‐Val‐OH (10) representing the partial sequence A80–A84 of human fibroblast interferon was synthesized using the newly developed allyl‐ester protection of carboxy functions. The allyl esters, which are stable to acids and to bases, can be cleaved under very mild, neutral conditions using tris(triphenylphosphine)rhodium(I) chloride or tetrakis(triphenylphosphine)palladium(0) as a catalyst. This synthetic method opens up a preparative route to glycopeptide model structures of glycoproteins of high biological interest.

Molybdenum(VI) complexes with malic acid: their inter-relationships, and the crystal structure of dicaesium bis[(S)-malato(2–)]-cis-dioxomolybdate(VI)–water (1/1)

The complex anions obtainable in salts crystallising from aqueous solutions of molybdate and malic acid (H3mal) are of the types (i)[MoO2(Hmal)2]2–, (ia)[MoO2(mal)2]4–, and (ii)[Mo4O11(mal)2]4– The formation of each type is dependent primarily upon the reactant ratio, M+ : Mo : H3mal. With the structure of the type (ii) anion already known, the structure of the (simpler) anion (i) was determined by X-ray analysis of its salt, Cs2[MoO2(Hmal)2]·H2O. The complex is mononuclear, with each malato-ligand co-ordinated through the deprotonated hydroxy group and the vicinal carboxy group to form a five-membered chelate ring. The second carboxylate group is not co-ordinated, but there is inter-anion H-bonding between the two carboxy functions. The structural features of class (i) and (ii) anions show the importance of ligand characteristics in determining the type of molybdenum-oxygen core which forms. Compositional and i.r. evidence relating to class (ia) indicates it to be derived from (i) through proton replacement.

1,3‐Dithian‐2‐yl Methyl Ester as Two‐Step Protecting Group for the Carboxy Function in Peptide Synthesis

Angewandte Chemie International Edition in EnglishVolume 22, Issue 1 p. 62-62 Communication 1,3-Dithian-2-yl Methyl Ester as Two-Step Protecting Group for the Carboxy Function in Peptide Synthesis† Prof. Dr. Horst Kunz, Corresponding Author Prof. Dr. Horst Kunz Institut für Organische Chemie der Universität, Johann-Joahim-Becher. Weg 18—20, D-6500 Mainz (Germany)Institut für Organische Chemie der Universität, Johann-Joahim-Becher. Weg 18—20, D-6500 Mainz (Germany)Search for more papers by this authorHerbert Waldmann, Herbert Waldmann Institut für Organische Chemie der Universität, Johann-Joahim-Becher. Weg 18—20, D-6500 Mainz (Germany)Search for more papers by this author Prof. Dr. Horst Kunz, Corresponding Author Prof. Dr. Horst Kunz Institut für Organische Chemie der Universität, Johann-Joahim-Becher. Weg 18—20, D-6500 Mainz (Germany)Institut für Organische Chemie der Universität, Johann-Joahim-Becher. Weg 18—20, D-6500 Mainz (Germany)Search for more papers by this authorHerbert Waldmann, Herbert Waldmann Institut für Organische Chemie der Universität, Johann-Joahim-Becher. Weg 18—20, D-6500 Mainz (Germany)Search for more papers by this author First published: January 1983 https://doi.org/10.1002/anie.198300621Citations: 10 † This work was supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie.—H. W. thanks the Adolf-Todt-Stiftung for a grant. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume22, Issue1January 1983Pages 62-62 RelatedInformation

Oxidative Cleavage of Benzyl Esters with Triarylamine Cation Radicals—Selective Deblocking of Protected Carboxy Functions

AbstractThe complete manuscript of this communication appears in: Angew. Chem. Suppl. 1982, 1730. DOI:10.1002/anie.198217300

Masking the carboxy group as a 2,6,7-trioxabicyclo[2.2.2]octane: application to the synthesis of alkylcobaloximes containing ester and carboxy groups

The hydrolytic stability of 2,6,7-trioxabicyclo-[2.2.2]octanes towards aqueous acid is intermediate between that of 1,1,1-triethoxyethane and 1-methyl-2,8,9-trioxa-adamantane; a synthetic application of this trioxabicyclo-octane group as a masked carboxy function is described.