Highly Enantioselective Transfer Hydrogenation of α‐Imino Esters by a Phosphoric Acid

Chiral phosphoric acids have been identified as highly efficient organocatalysts for the asymmetric transfer hydrogenation of α‐imino esters and amide. Utilizing Hantzsch esters as the hydrogen donor, versatile highly enantioenriched α‐amino esters and their derivatives were obtained with up to 98 % ee.     

Hydriodic Acid Reduction of α-Ketol and α-Diketo Fatty Acids

The hydriodic acid reduction of α-ketol and α-diketo derivatives of three monoethenoid fatty acids, oleic, petroselinic and erucic acids, has been studied. The formation of an isomeric mixture of monoketo acids in each has been established by characterization of monocarboxylic or dicarboxylic acids, the hydrolysed fragments of Beckmann rearrangement of the corresponding oximes of monoketo acids, by thin-layer chromatography (TLC). Hydriodic acid has been found to be a satisfactory reagent for the synthesis of monoketo acids from the α-ketol and α-diketo acids.     

Enantioselective Phase‐Transfer Catalytic α‐Benzylation and α‐Allylation of α‐tert‐Butoxycarbonyllactones

A new enantioselective α‐benzylation and α‐allylation of α‐tert‐butoxycarbonyllactones was devloped. α‐Benzylation and α‐allylation of α‐tert‐butoxycarbonylbutyrolactone and α‐tert‐butoxycarbonylvalerolactone under phase‐transfer catalytic conditions (50% cesium hydroxide, toluene, −60 °C) in the presence of (S,S)‐3,4,5‐trifluorophenyl‐NAS bromide (1 mol%) afforded the corresponding α‐substituted α‐tert‐butoxycarbonyllactones in very high chemical yields (up to 99%) and optical yields (up to 99% ee). The synthetic potential of this method has been successfully demonstrated by the asymmetric synthesis of unnatural α‐quaternary homoserines, 3‐alkyl‐3‐carboxypyrrolidine and 3‐alkyl‐3‐carboxypiperidine.     

DL-homoserinehydroxamic Acid,DL-homo-cystinedihydroxamic Acid,and Derivatives by Hydroxylaminolysis of γ-Hydroxy- and γ-Thio-Lactones

The reaction of α-amino-, α-carbamoylamino-, α-benzamido-, and α-benzyloxycarbonyl-amino-γ-butyrolactone with hydroxylamine led to the formation of DL-homoserinehydroxamic acid and α-N-acyl derivatives. α-N-Benzoyl-DL-homoserine-N-methyl-hydroxamic acid and O-benzylhydroxamic acid ester were prepared by reacting α-benzamido-γ-butyrolactone with N-methylhydroxylamine and with O-benzylhydroxylamine, respectively. Hydroxyl-aminolysis of DL-homocysteinethiolactone and of N-acyl-DL-homocysteinethiolactones gave homocystinedihydroxamic acid and N,N′-disubstituted derivatives. Relative reactivities of O- and S-lactones were compared.     

Efficient Synthesis of β,γ‐Alkynyl α‐Amino Acid Derivatives by Ag(I)‐Catalyzed Alkynylation of α‐Imino Esters

The first catalytic synthesis of β,γ‐alkynyl α‐amino acid derivatives was achieved by direct addition of terminal alkynes to α‐imino esters in the presence of an Ag(I) salt under mild reaction conditions.     

Poly(α,α,α′,α′-tetrafluoro-p-xylylene)

Poly(α,α,α′,α′-tetrafluoro-p-xylylene) was prepared by the pyrolysis of cyclo-di-(α,α,α′,α′-tetrafluoro-p-xylylene) and by the pyrolysis of α,α′-bis(alkylsulfonyl)-α,α,α′,α′-tetrafluoro-p-xylene. The pyrolysis of α,α′-dibromo-α,α,α′,α′-tetrafluoro-p-xylylene also gave the polymer, but the method is less satisfactory. Poly(α,α,α′,α′-tetrafluoro-p-xylylene) shows remarkable thermal and oxidative stability at elevated temperatures. Useful mechanical and electrical properties are retained after aging for 3000 hr at 250° in air. After initial change due to crystallization, tensile strength remains near 10,000 psi, elongation above 5%, and dielectric constants and dissipation factors at approximately 2.4 and .001, respectively.     

Photochemistry of α,α′-Disubstituted Azoalkanes. I. Photosolvolytic Inversion and Substitution of α,α′-Dichloro- and α,α′-Dialkoyloxyazoalkanes

A series of α,α′-dichloro (α DClA), α,α′-dialkoyloxy- (αDAlA) and α,α′-dibenzoxy-azoalkanes (αDBeA) without α-aryl substituents was found to undergo meso ? dl photointerconversion upon direct irradiation through Pyrex in the presence of oxygen in a number of solvents. Furthermore, irradiation of α,α′-dipropionoxy-azoalkanes in benzene in the presence of excess acetic acid leads to substitution of the propionoxy groups by acetoxy groups in addition to meso ? dl photointerconversion. Similar irradiation in the presence of CH₃CO₂D does not lead to deuterium substitution of the β-hydrogens. The presence of benzenethiol radical scavenger does not affect the course of these photoreactions. Photosolvolysis schemes involving heterolysis (in the case of αDAlA and αDBeA) or an unstable intermediate (in the case of αDClA) are proposed.     

Catalytic Asymmetric Synthesis of Functionalized α,α‐Disubstituted α‐Amino Acid Derivatives from Racemic Unprotected α‐Amino Acids via in‐situ Generated Azlactones

Masked and activated highly enantioenriched α,α‐disubstituted α‐amino acids with an additional adjacent stereocenter were formed by a tandem reaction involving five steps using racemic unprotected amino acid substrates. Key step is the 1,4‐addition of in‐situ generated azlactones to a broad number of enones. The products of this step‐economic route can, e.g., be useful for a divergent and rapid access to biologically interesting unnatural glutamic acid derivatives.     

Asymmetric Synthesis of 3,4‐Dihydrocoumarins Bearing an α,α‐Disubstituted Amino Acid Moiety

An organocatalytic approach for the stereoselective synthesis of 3,4‐dihydrocoumarins with an α,α‐disubstituted amino acid moiety incorporated is presented. The developed methodology is based on the cascade reaction between α‐substituted azlactones and 2‐hydroxychalcones. It is initiated by a chiral Brønsted base‐catalyzed enantio‐ and diastereoselective Michael reaction followed by the azlactone ring opening to construct a 3,4‐dihydrocoumarin framework. Products bearing two adjacent stereogenic centers, one being quaternary, were formed with high enantioselectivities and excellent diastereoselectivities. Furthermore, the complete regioselectivity of the new cascade reactivity is worthy of notice.

     

Stereo‐Controlled Asymmetric Bioreduction of α,β‐Dehydroamino Acid Derivatives

α,β‐Dehydroamino acid derivatives proved to be a novel substrate class for ene‐reductases from the ‘old yellow enzyme’ (OYE) family. Whereas N‐acylamino substituents were tolerated in the α‐position, β‐analogues were generally unreactive. For aspartic acid derivatives, the stereochemical outcome of the bioreduction using OYE3 could be controlled by variation of the N‐acyl protective group to furnish the corresponding (S)‐ or (R)‐amino acid derivatives. This switch of stereopreference was explained by a change in the substrate binding, by exchange of the activating ester group, which was proven by ²H‐labelling experiments.     

Structure Determination of Derivatives of α-Amino-α, α-Diphenylacetamide by Mass Spectrometry

The mass spectral fragmentation pattern of a series of derivatives of α-amino-α,α-diphenylacetamide of the types A and B is described. The fragmentation of some related benzhydryl ureas (C) is also included.     

Combined Biocatalytic and Chemical Transformations of Oleic Acid to ω‐Hydroxynonanoic Acid and α,ω‐Nonanedioic Acid

A practical chemoenzymatic method for the synthesis of 9‐hydroxynonanoic acid and 1,9‐nonanedioic acid (i.e., azelaic acid) from oleic acid [(9Z)‐octadec‐9‐enoic acid] was investigated. Biotransformation of oleic acid into 9‐(nonanoyloxy)nonanoic acid via 10‐hydroxyoctadecanoic acid and 10‐keto‐octadecanoic acid was driven by a C‐9 double bond hydratase from Stenotrophomonas maltophilia, an alcohol dehydrogenase from Micrococcus luteus, and a Baeyer–Villiger monooxygenase (BVMO) from Pseudomonas putida KT2440, which was expressed in recombinant Escherichia coli. After production of the ester (i.e., the BVMO reaction product), the compound was chemically hydrolyzed to n‐nonanoic acid and 9‐hydroxynonanoic acid because n‐nonanoic acid is toxic to E. coli. The ester was also converted into 9‐hydroxynonanoic acid and the n‐nonanoic acid methyl ester, which can be oxygenated into the 9‐hydroxynonanoic acid methyl ester by the AlkBGT from P. putida GPo1. Finally, 9‐hydroxynonanoic acid was chemically oxidized to azelaic acid with a high yield under fairly mild reaction conditions. For example, whole‐cell biotransformation at a high cell density (i.e., 10 g dry cells/L) allowed the final ester product concentration and volumetric productivity to reach 25 mM and 2.8 mM h⁻¹, respectively. The overall molar yield of azelaic acid from oleic acid was 58%, based on the biotransformation and chemical transformation conversion yields of 84% and 68%, respectively.

     

Separation of α‐Lactalbumin and β‐Lactoglobulin by a Convenient Liquid‐Solid Extraction System: Application to Milk Whey

A liquid‐solid extraction system based on Tween 80/phosphate was developed. Under the optimized conditions (9 wt % Tween 80, 1.6 : 1 (molar ratio) K₂HPO₄ : NaH₂PO₄, 1.25 mol/L total phosphate, pH = 7.4), α‐Lactalbumin (α‐La) and β‐Lactoglobulin (β‐Lg) were separated with recovery rates of 87.6 % (in the solid polymeric phase) and 98.2 % (in the salt aqueous phase), respectively. Under the effects of water and salt, the solid phase had the ability to form a new liquid‐solid extraction system, and 85.1 % of α‐La could be reversely extracted into the new salt aqueous phase. Following dialysis against water, proteins obtained through extraction and reverse extraction, were analyzed by polyacrylamide gel electrophoresis (PAGE) and thin‐layer scanning. The method was applied successfully to separate α‐La and β‐Lg from milk whey.     

Kinetic Resolution of Aliphatic β‐Amino Acid Amides by β‐Aminopeptidases

Access to enantiopure β‐amino acids : β‐Aminopeptidases are hydrolases that possess the unique ability to cleave N‐terminal β‐amino acids from peptides and amides. Hydrolysis of racemic β‐amino acid amides catalyzed by these enzymes displays enantioselectivity with strong preference for substrates with the L ‐configuration, and gives access to various aliphatic β‐amino acids of high enantiopurity.

     

Prostaglandins and prostaglandin intermediates. XIV. Synthesis of rac-9α, 11α, 13α-trihydroxy- and rac-9α, 11α, 13β-Trihydroxy-5(Z)-prosten-15-ynoic Acid

Attempts to rearrange a β-hydroxy-alkyne with a secondary hydroxy group into an α,β-unsaturated ketone failed in the case of a potential prostaglandin intermediate. However, it was possible to convert this intermediate into 13-hydroxy-5(Z)-prosten-15-ynoic acids, which are interesting prostaglandin analogues with a modified alkyl side chain.     

Synthesis of α, α′, β-trideuterovinyl acetate

Reaction conditions for the synthesis of α, α′, β-trideuterovinyl acetate by the continuous vapour phase catalytic reaction of deuteroacetylene and acetic acid-d (CH₃COOD) are described.     

Radiation-induced copolymerization of α,β,β-trifluoroacrylonitrile with α-olefin

Homopolymerization and copolymerization of α,β,β-trifluoroacrylonitrile (FAN) with γ-olefins were carried out in bulk by γ-ray irradiation at 25°C. FAN gives very small quantities of brown and greasy low molecular weight polymer. Cyano groups in FAN polymer were found to be readily hydrolyzed to acid amide groups in the atmosphere. FAN was found to copolymerize with ethylene, propylene, and isobutylene via a radical mechanism to form equimolar copolymers in a wide range of monomer compositions. The polymerization rate increases linearly with FAN fraction in the monomer mixture. These copolymers are also hydrolyzed in the atmosphere, and the hydrolysis proceeds with more difficulty for the copolymer with higher α-olefin. The reactivity ratios r₁ (FAN) and r₂ (α-olefin) were determined to be 0.01 and 0.12 for the FAN/ethylene copolymerization and 0.01 and 0.07 for the FAN/propylene copolymerization. These results confirm that an alternating copolymerization takes place in the FAN/α-olefin system.