An efficient conversion of carboxylic acids to one-carbon degraded aldehydes via 2-hydroperoxy acids

After the formation of dianions of a carboxylic acid with lithium diisopropylamide, oxygen was bubbled into the solution to produce 2-hydroperoxy acid. Then the reaction mixture was acidified with a 2 N HCl solution and subsequently elevated to 50 degrees C to afford the aldehyde with the loss of one carbon atom. Even saturated (C(10)-C(20)) and unsaturated (C(18:1)) carboxylic acids were converted into the odd aldehydes (C(9)-C(19), C(17:1)) in high yields. This conversion was found to be an efficient method for the preparation of carboxylic acids (Cn) to one-carbon degraded aldehydes (Cn-1) via 2-hydroperoxy acids.     

An Efficient Conversion of Carboxylic Acids to One-Carbon Degraded Aldehydes via 2-Hydroperoxy Acids

After the formation of dianions of a carboxylic acid with lithium diisopropylamide, oxygen was bubbled into the solution to produce 2-hydroperoxy acid. Then the reaction mixture was acidified with a 2 N HCl solution and subsequently elevated to 50 °C to afford the aldehyde with the loss of one carbon atom. Even saturated (C₁₀–C₂₀) and unsaturated (C_18:1) carboxylic acids were converted into the odd aldehydes (C₉–C₁₉, C_17:1) in high yields. This conversion was found to be an efficient method for the preparation of carboxylic acids (Cn) to one-carbon degraded aldehydes (Cn-1) via 2-hydroperoxy acids.     

Synthesis of DL- and D-gluco-hept-3-ulose.

DL-gluco-Hept-3-ulose was synthesised by oxidation of tri-O-isopropylidene-meso-glycero-gulo-heptitol with methyl sulphoxide-phosphorus pentaoxide, and subsequent hydrolysis. D-gluco-Hept-3-ulose (3) was synthesised by oxidation of one of the two isopropylidene derivatives from perseitol (D-glycero-D-galacto-heptitol), which is presumed to have the 2,2:4,5:6,7 structure, followed by hydrolysis. The crude product from the reduction of DL-gluco-hept-3-ulose with sodium borohydride showed two peaks corresponding to meso-glycero-gulo-heptitol and perseitol on g.l.c. of the trimethylsilyl derivatives. Isolation and acetylation of the latter heptitol revealed it to be racemic perseitol. Oxodation of DL-gluco-hept-3-ulose with oxygen in alkali followed by treatment with ferric acetate-hydrogen peroxide gave products with chromatographic behaviour characteristic of arabinonolactone and erythrose. Treatment of DL-gluco-hept-3-ulose with 2,4-dinitrophenylhydrazine gave a 1-deoxy-2,4-dinitrophenylosazone.     

Stereoselective reduction of C-2 substituted steroid C-3 ketones with lithium tris-(R,S-1,2-dimethylpropyl)-borohydride and sodium borohydride

The effect of C-2 substitution on the stereoselective reduction of steroid C-3 ketones with lithium tris-(R,S-1,2-dimethylpropyl)-borohydride and sodium borohydride was investigated. The C-2 mono- and di-substituted chloro and methyl derivatives were predominantly reduced to one of the epimeric alcohols. The 2 alpha-chloro and 2 alpha-methyl derivatives of 17 beta-acetoxy-5 alpha-androstan-3-one undergo stereoselective reduction with lithium tris-(R,S-1,2-dimethylpropyl)-borohydride to the axial (3 alpha) alcohol as observed in the unsubstituted compound, whereas sodium borohydride gives predominantly the equatorial (3 beta) alcohol. The 2 beta-chloro, 2 beta-methyl, 2,2-dichloro, and 2,2-dimethyl derivatives are reduced predominantly to the equatorial (3 beta) alcohol by both reagents.     

Synthesis,Structure, and Biological Applications of α‐Fluorinated β‐Amino Acids and Derivatives

This review gives a broad overview of the state of play with respect to the synthesis, conformational properties, and biological activity of α‐fluorinated β‐amino acids and derivatives. General methods are described for the preparation of monosubstituted α‐fluoro‐β‐amino acids (Scheme 1). Nucleophilic methods for the introduction of fluorine predominantly involve the reaction of DAST with alcohols derived from α‐amino acids, whereas electrophilic sources of fluorine such as NFSI have been used in conjunction with Arndt? Eistert homologation, conjugate addition or organocatalyzed Mannich reactions. α,α‐Difluoro‐β‐amino acids have also been prepared using DAST; however, this area of synthesis is largely dominated by the use of difluorinated Reformatsky reagents to introduce the difluoro ester functionality (Scheme 9). α‐Fluoro‐β‐amino acids and derivatives analyzed by X‐ray crystal and NMR solution techniques are found to adopt preferred conformations which are thought to result from stereoelectronic effects associated with F located close to amines, amides, and esters (Figs. 2–6). α‐Fluoro amide and β‐fluoro ethylamide/amine effects can influence the secondary structure of α‐fluoro‐β‐amino acid‐containing derivatives including peptides and peptidomimetics (Figs. 7–9). α‐Fluoro‐β‐amino acids are also components of a diverse range of bioactive anticancer (e.g., 5‐fluorouracil), antifungal, and antiinsomnia agents as well as protease inhibitors where such fluorinated analogs have shown increased potency and spectrum of activity.     

An improved preparation of 3-deoxy-d-erythro-hexos-2-ulose via the bis(benzoylhydrazone) and some related constitutional studies

Sugar osazones and glycosuloses rapidly and quantitatively react with hydroxylamine to produce oximes that give trimethylsilyl derivatives suitable for g.l.c. and mass spectral analysis. The reaction of d-glucose with benzoylhydrazine to give the bishydrazone of 3-deoxy-d-erythro-hexos-2-ulose (1) [H. El Khadem et al., Carbohydr. Res., 22 (1973) 381-89] was re-investigated, together with the conversion of this compound to the hexosulose. Although by-products are produced in the reaction, including the bis(benzoylhydrazone) (osazone) of d-glucose, the major product is the monohydrate of the bis(benzoylhydrazone) of 1 (colorless). The anhydrous (yellow) form can be prepared from the monohydrate by crystallization from absolute ethanol and has quite different physical properties. Improvements of the original preparation are described that allow the preparation of the bishydrazone and its subsequent conversion to 1via transhydrazonation in 44% overall yield, and with no detectable contamination by d-glucose or d-glucosone. Evidence is presented that the previously reported cyclic form of the bis(benzoylhydrazone) of d-glucose is the bis(benzoylhydrazone) (monohydrate) of 1.     

Aromatic amino acids and their derivatives as ligands for the isolation of aspartic proteinases

Affinity chromatography was used to study an interaction of aspartic proteinases with immobilized aromatic amino acids and their derivatives. The following ligands were used: L-tyrosine, 3-iodo-L-tyrosine, 3,5-diiodo-L-tyrosine, L-phenylalanine, p-iodo-L-phenylalanine and N-acetyl-L-phenylalanine. With the exception of the last one, ligands were coupled directly to divinyl sulfone activated Sepharose 4B. For the preparation of immobilized N-acetyl-L-phenylalanine, divinyl sulfone activated Sepharose 4-B with linked ethylene diamine was used. Porcine pepsin was used for the evaluation of the capacity of the prepared affinity carriers. The capacity of the immobilized amino acid derivatives significantly increased in comparison with the non-derivatized amino acids. The prepared immobilized ligands were further used for the separation of human pepsinogens.     

Vacuum ultraviolet spectroscopy of poly-α-amino acids

Vacuum ultraviolet spectra are reported for a series of poly-α-amino acids which were film cast onto lithium fluoride discs. The solvents used for film casting were chosen such that chain conformations representative of those normally found for polypeptides were produced. Comparison of the spectra obtained suggests that the peptide group has at least one conformationally sensitive transition in the vacuum ultraviolet region at ～165 nm. For the β, or extended, form of the polymers, the intensity of this transition appears to be greater than that found for the monomer units, whereas the formation of a more compact helix results in a reduction in the intensity of this transition relative to that found for the monomers.     

食用菌鲜味物质研究进展

本文介绍了食用菌鲜味物质的研究进展,可以为食用菌调味品的开发提供理论基础和指导。文章主要综述了食用菌鲜味物质氨基酸和核苷酸的组成、呈鲜特点、提取以及食用菌在调味品中的开发现状。食用菌中氨基酸和核苷酸类的含量都比较高,是食用菌重要的鲜味物质。这些鲜味物质的酶法提取比传统方法的效果好、提取率高。当今食用菌调味品生产工艺简单,大多为粗加工品,且食用菌中的鲜味物质和其它的功能性成分没有充分释放出来,需要研发新方法来充分释放其中的鲜味物质及其它的营养成分,并且要加强食用菌抽提物产品研制的新技术。     

Human interferon-γ lacking 23 COOH-terminal amino acids is biologically active

We constructed five mutated cDNAs encoding human interferon-γ (IFN-γ) derivatives lacking 19–23 COOH-terminal residues and expressed them in Escherichia coli. All the derivatives were purified to homogeneity. They showed substantially the same order of antiviral activity in vitro as the intact molecule, and behaved as a dimer. The far- and near-UV circular dichroism spectra of the derivatives were quite similar to those of the intact one. These results indicate that the 23 COOH-terminal amino acids at least are not essential for achieving the full antiviral activity and constructing the higher structure of human IFN-γ.     

Unexpected formation of complex bridged tetrazoles via intramolecular 1,3-dipolar cycloaddition of 1,2-O-cyanoalkylidene derivatives of 3-azido-3-deoxy-D-allose

An unexpected and interesting intramolecular side reaction occurred during the attempted synthesis of glycosyl cyanides upon treatment of 1-O-acetyl-3-azido-3-deoxyallose derivatives with TMSCN and different Lewis acids. Exo-1,2-O-cyanoalkylidene derivatives formed by neighboring group participation and attack of cyanide underwent, after Lewis-acid mediated isomerization to the endo-isomer, intramolecular azide-cyanide cycloaddition leading to the formation of tetrazoles embedded in bridged tetracyclic ring systems. The efficiency of cycloaddition is dependent on the ring structure of the sugar (pyranose or furanose). Of the studied molecules, 3-azido-1,2-O-cyanoethylidene-3-deoxy-allopyranose provides the most suitable scaffold for intramolecular [2+3] cycloaddition under exceptionally mild conditions. Our results highlight the capability of carbohydrates to act as scaffolds for the precise positioning of functional groups productive for a specific chemical reaction.     

Lithium hydroxide/aqueous methanol: mild reagent for the hydrolysis of bile acid methyl esters

An efficient and convenient procedure for the hydrolysis of bile acid methyl esters is described. This is achieved by the addition of aqueous lithium hydroxide in methanol/dioxane (or tetrahydrofuran) at room temperature. Under these conditions, the formates as well as the acetate derivatives were also hydrolyzed, and the desired bile acids were isolated in 86 to 94% yield.     

A facile preparation of α-hydroxy fatty acids

A convenient, one-step synthesis of α-hydroxy long chain, very long-chain and branched chain fatty acids from non-oxygenated fatty acids is described. The procedure involves preparation of fatty acid dianion using lithium diisopropylamide and oxygenation of the dianion by molecular oxygen.     

The Schöllkopf chiron and transition metal mediated reactions,a powerful combination for stereoselective construction of cyclic α-quaternary-α-amino acid derivatives

The focus has been on the development of methodology for stereoselective preparation of spiroannulated intermediates of the Sch?llkopf chiron and further transformations to cyclic alpha-amino acids. The spiroannulations are effected by Ru(II)-catalysed ring-closing metathesis reactions, by Ru(II)- and Pd(0)-catalysed cycloisomerisations, by Rh(II)-carbenoid cyclisation reactions and by intramolecular aldol condensations. Hydrolytic reactions of the spirane intermediates have provided several groups of highly novel and functionalised five-, six- and seven-membered cyclic alpha-quaternary-alpha-amino acid derivatives as well as alicyclic derivatives. The novel cyclic amino acid derivatives can be regarded as cyclic constrained analogues of corresponding common amino acids, or in some cases as intermediates for further preparation of such amino acids. Some emphasis has been on the preparation of cyclic serine analogues. Major efforts have been on the preparation of cyclic alpha-quaternary bis(alpha-amino acid) derivatives as conformationally constrained dicarba-analogues of cystine.     

A convenient procedure for the synthesis of ceramides

A procedure for the preparation of ceramides by direct coupling of long-chain bases and fatty acids in the presence of a mixed carbodiimide is described. This method has been used to prepare ceramides containing sphing-4-enine or sphinganine and various saturated and unsaturated fatty acids as well as saturated 2-hydroxy acids. Ceramides containing 4-hydroxy sphinganine and saturated nonhydroxy acids have also been prepared. The yields were 60-75%. The characterization of these compounds by gas-liquid chromatography-mass spectrometry as trimethylsilyl derivatives has been previously reported. Some of the ceramides are further characterized in this report by infrared spectroscopy and one compound, in addition, by elementary analysis. Use of racemic constituents for 2-hydroxy acid ceramide syntheses leads to the formation of diastereoisomers which separate by thin-layer chromatography. These were characterized by gas-liquid chromatography-mass spectrometry as the trimethylsilyl derivatives and by infrared spectroscopy. Their configurations were established by syntheses with optically active constituents.     

In vitro metabolism of estrone 2,4,6,7-3H and 4-androstene-3,17-dione-1,2-3H in submandibular gland and submandibular gland cancer tumor

Tritiated estrone and 4-androstene-3, 17-dione were incubated with slices of human submandibular gland and submandibular gland cancer tumor. Metabolites were separated by paper and thin layer chromatography. Estradiol-17β and testosterone were identified as metabolites. The metabolites were identified by reverse isotope dilution and the preparation of derivatives (formation of acetates). The amounts of estradiol-17β and testosterone formed in the tumor were significantly higher than that formed in the submandibular gland.     

S,X-acetals in nucleoside chemistry. III. Synthesis of 2'- and 3'-O-azidomethyl derivatives of ribonucleosides

2'- and 3'-O-azidomethyl derivatives of ribonucleosides were obtained by splitting the corresponding methylthiomethyl derivatives of ribonucleosides with bromine or SO2Cl2 followed by lithium azide treatment.     

On‐resin conversion of Cys(Acm)‐containing peptides to their corresponding Cys(Scm) congeners

The Acm protecting group for the thiol functionality of cysteine is removed under conditions (Hg²⁺) that are orthogonal to the acidic milieu used for global deprotection in Fmoc‐based solid‐phase peptide synthesis. This use of a toxic heavy metal for deprotection has limited the usefulness of Acm in peptide synthesis. The Acm group may be converted to the Scm derivative that can then be used as a reactive intermediate for unsymmetrical disulfide formation. It may also be removed by mild reductive conditions to generate unprotected cysteine. Conversion of Cys(Acm)‐containing peptides to their corresponding Cys(Scm) derivatives in solution is often problematic because the sulfenyl chloride reagent used for this conversion may react with the sensitive amino acids tyrosine and tryptophan. In this protocol, we report a method for on‐resin Acm to Scm conversion that allows the preparation of Cys(Scm)‐containing peptides under conditions that do not modify other amino acids. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.     

The formation of 2-hydroxy-4-hydroxymethyl-3-(indol-3-yl)-cyclopent-2-enone derivatives from ascorbigens

A facile preparation is described of 3-(indol-3-yl)-2-hydroxy-4-hydroxymethylcyclopent-2-enone and its N-derivatives in 15-40% yields by the degradation of ascorbigen or its N-derivatives in a warm solution of L-ascorbic acid through a sequential domino reaction. The same cyclopentenone derivatives were obtained in 30-40% yields by the condensation of (N-alkylindol-3-yl)glycolic acids with ascorbic acid. 2,6-Dihydroxy-1-(indol-3-yl)hexa-1,4-diene-3-one and 2-hydroxy-4-hydroxymethyl-5-(indol-3-yl)cyclopent-2-enone were identified as intermediates in this reaction.     

Coenzyme A derivatives of bile acids-chemical synthesis, purification, and utilization in enzymic preparation of taurine conjugates.

Synthesis of the coenzyme A derivatives of bile acids by the mixed anyhydride method results in a product that is contaminated by unreacted CoASH and bile acid. These compounds can be purified by Sephadex LH-20 chromatography. In each case, the purified product is free of starting materials and exhibits an equimolar ratio of bile acid, coenzyme A, and thioester bond. Millimolar extinction coefficients were calculated for these compounds as A259 nm, 15.03 +/- 0.58; A232 nm, 7.60 +/- 0.17; and A232 nm for the thioester bond, 4.12 +/- 0.17. These CoA derivatives were hydrolyzed in strongly alkaline solution, but were stable at physiologic temperature and pH. Utilization of these compounds in the enzymic preparation of taurine conjugates of bile acids indicated 94% activity. These purified CoA derivatives may be useful in studying the enzymic conjugation of bile acids.