Improved High-Fat Diet-Induced Glucose Intolerance by an Oral Administration of Phytosphingosine

The optical resolution of (±)-2,2,2-trifluoro-1-(1-pyrenyl)ethanol was achieved by using lipases. In particular, Pseudomonas aeruginosa lipase (lipase LIP) showed high enantioselectivity (E = > 100) and reactivity in the alcoholysis of the chloroacetyl ester of the title compound. The reactivity of the lipase LIP-catalyzed enantioselective alcoholysis of the chloroacetate with 1-hexanol was much higher than that of the acetylating the alcohol with vinyl acetate.     

Synthesis and Antimalarial Activity of Some New 1,2-Dioxolane Derivatives

The synthesis of 1,2-dioxolane derivatives in two different acetophenone series, as simplified models of natural coumarins is described. 2-Acetyl-3-acetoxy-4-(3-hydroperoxy-3-methylbut-1-enyl)phenyl acetate and 2-acetyl-5-acetoxy-4-(3-hydroperoxy-3-methylbut-1-enyl) phenyl acetate synthons are used as precursors to these structures. In vitro antimalarial activity of the 1,2-dioxolane derivatives has been investigated.     

Lipase-catalyzed optical resolution of trifluoro(aryl)ethanols

Optical resolutions of racemic 2,2,2-trifluoro-1-(aryl)ethanols — (1-naphthyl), (2-naphthyl), (4-methylnaphthyl), (phenyl), (1-pyrenyl) — were achieved by lipase-catalyzed enantioselective acetylations with vinyl acetate as an acetyl donor in octane, and (S)-acetates and (R)-alcohols were obtained. Among the lipases tested, lipase from Pseudomonas aeruginosa (lipase LIP, Toyobo) showed good enantioselectivity for above ethanols. However, no acetylation occurred with sterically hindered alcohols — (9-phenanthryl), (9-anthryl), (2-methylnaphthyl), (2, 4, 6-trimethylphenyl) — by various lipases. The resolutions of the three alcohols were carried out by the enantioselective alcoholysis or hydrolysis of their chloroacetates by lipase LIP.     

Specificity of Candida antarctica lipase B (SP 435) in the presence of lipase A in a double enantioselective transesterification

Summary In the lipase-catalyzed double enantioselective transesterification between the meso-diol 1 and the racemic 2,2,2-trifluoroethyl 2-chloropropanoate (rac-2) by the immobilized lipase preparation SP 382 from Candida antarctica, consisting of the components A and B, component B only is responsible for the enantioselectivity.     

Long-chain ethers as solvents can amplify the enantioselectivity of the Carica papaya lipase-catalyzed transesterification of 2-(substituted phenoxy)propanoic acid esters

The enantioselectivity of the transesterification of the 2,2,2-trifluoroethyl esters of 2-(substituted phenoxy)propanoic acids, as catalyzed by the lipase from Carica papaya, was greatly improved by using long-chain ethers, such as di-n-hexyl ether, as solvents instead of the conventional diisopropyl ether. Thus, for example, the E value was enhanced from 21 [in diisopropyl ether (0.8 ml)] to 57 [in di-n-hexyl ether (0.8 ml)] in the reaction of 2,2,2-trifluoroethyl(RS)-2-phenoxypropanoate (0.1 mmol) with methanol (0.4 mmol) in the presence of the plant lipase preparation (10 mg); it was also improved from 13 (in diisopropyl ether) to 44 (in di-n-hexyl ether) in the reaction of 2,2,2-trifluoroethyl(RS)-2-(2-chlorophenoxy)propanoate with methanol under the same reaction conditions.     

Halo lipids, 8. Synthesis of O-alkyl-O-alkyl-O-(2,2,2-trifluoroethyl)glycerols and O-alkyl-O-(2,2,2-trifluoroethyl)glycero-phosphocholines

The syntheses and structure determination of 3 positional isomers of O-alkyl-O-(2,2,2,-trifluoroethyl)glycerols and their conversion into the corresponding O-alkyl-O-(2,2,2-trifluoroethyl)glycerophosphocholines via the [O-alkyl-O-(2,2,2-trifluoroethyl)glycero]-2-bromoethyl hydrogen phosphates are described.     

Lipase catalyzed polytransesterification in an organic solvent

Summary Lipase-catalyzed polytransesterification ofbis(2,2,2-trifluoroethyl) dodecanedioate with aliphatic diols (from 1,2-ethanediol to 1,6-hexanediol) was studied with 4 enzymes and a number of solvents. The effects of experimental parameters were investigated with the purpose of obtaining a polyester of as high as possible average molar mass. The highest mass average molar mass (M _w) of 34,750 g mol^-1 (DP = 122) was obtained under vacuum with 1,4-butanediol,Mucor miehei lipase, and diphenyl ether as solvent.     

Regio- and enantio-selective acetylation of 3,3,3-trifluoro-2-arylpropane-1,2-diols using Candida antarctica lipase

Of nine commercially available lipases, lipase SP 435 from Candida antarctica, showed moderate enantioselectivity (E=17) for acetylation of racemic 3,3,3-trifluoro-2-phenylpropane-1,2-diol, 2, with vinyl acetate in diisopropyl ether (S selectivity). The other eight had low selectivities, with E values below 10. The selectivity and reactivity of SP 435 for 2 was markedly improved in dichloroethane (E=41). Moreover, SP 435 had moderate to high selectivity for the related compounds 3,3,3-trifluoro-2-(1-naphthyl)-propane-1,2-diol, 4, (E=20), 3,3,3-trifluoro-2-(indol-3-yl)propane-1,2-diol, 6, (E=80), and 3,3,3-trifluoro-2-(pyrrol-2-yl)-propane-1,2-diol, 8, (E=17).     

Hydrolytic resolution of (R,S)-naproxen 2,2,2-trifluoroethyl thioester by Carica papaya lipase in water-saturated organic solvents

For the first time, the Carica papaya lipase (CPL) stored in crude papain is explored as a potential enantioselective biocatalyst for obtaining chiral acids from their racemic thioesters. Hydrolytic resolution of (R,S)-naproxen 2,2,2-trifluoroethyl thioester in water-saturated organic solvents is employed as a model system for studying the effects of temperature and solvents on lipase activity and enantioselectivity. An optimal temperature of 60 degrees C, based on the initial rate of (S)-thioester and a high enantiomeric ratio (i.e., E-value defined as the ratio of initial rates for both substrates) of >100 at 45 degrees C in isooctane, is obtained. Kinetic analysis, considering product inhibition and enzyme deactivation, is also performed, showing agreement between the experimental and best-fit conversions for (S)-thioester. A comparison of the kinetic and thermodynamic behaviors of CPL and Candida rugosa lipase (CRL) in isooctane and cyclohexane indicates that both lipases are very similar in terms of thermodynamic parameters DeltaDeltaH and DeltaDeltaS, initial rate of (S)-substrate, and E-value when (R,S)-naproxen 2,2,2-trifluoroethyl thioester or ester is employed as substrate.     

Oxiranylphenyl esters from Pimpinella diversifolia

The major components of the essential oil from roots of Pimpinella diversifolia, gathered in the Kumaun Region of India, have been identified as the (+)-Z-2-methyl-2-butenoate (angelate) and (+)-isobutyrate esters of 4-methoxy-2-(E-3-methyloxiranyl)phenol. Aromatic ¹³C NMR resonances of these compounds and their synthetic acetate analog, as well as those of 2-methoxy-4-(E-3-methyloxiranyl)phenyl acetate prepared from isoeugenol, were found to be in excellent agreement with calculated values. Comparison of the EIMS of the natural and synthetic products with those reported for compounds previously identified as 2-methoxy-4-(E-3-methyloxiranyl)phenyl esters indicates that they also have the 4-methoxy-2-(E-3-methyloxiranyl)phenyl structure.     

Syntheses of Four Methyl-branched Secondary Acetates and a Methyl-branched Ketone as Possible Candidates for the Female Pheromone of the Screwworm Fly,Cochliomyia hominivorax

6-Acetoxy-19-methylnonacosane (1), 7-acetoxy-19-methylnonacosane (2), 8-acetoxy-19-methylnonacosane (3), 7-acetoxy-15-methylnonacosane (4), and 21-methyl-7-hentriacontanone (5) were synthesized as racemic and diastereomeric mixtures. These are new compounds isolated from an HPLC fraction of the female hexane extract which elicited mating responses in the male screwworm fly, Cochliomyia hominivorax.     

Synthesis and antimalarial activity of some new 1,2-dioxolane derivatives

The synthesis of 1,2-dioxolane derivatives in two different acetophenone series, as simplified models of natural coumarins is described. 2-Acetyl-3-acetoxy-4-(3-hydroperoxy-3-methylbut-1-enyl)phenyl acetate and 2-acetyl-5-acetoxy4-(3-hydroperoxy-3-methylbut-1-enyl) phenyl acetate synthons are used as precursors to these structures. In vitro antimalarial activity of the 1,2-dioxolane derivatives has been investigated.     

Polyethylene glycol-modified lipase catalyzes asymmetric alcoholysis of δ-decalactone in n-decanol

Summary Lipase from Pseudomonas cepacia was modified with 2,4-bis[O-methoxypoly(ethylene glycol)]-6-chloro-s-triazine(activated PEG₂) to form PEG-lipase. The PEG-lipase, soluble and active in organic solvents, catalyzes asymmetric alcoholysis of racemic -decalactone in alcohols to form (R)-5-hydroxydecanoic acid alkyl esters. The yield was 69% with 83% enantiomeric excess after 3 hr-reaction in n-decanol at 50°C. The advantage of this reaction is that the alcoholysis proceeds efficiently in straight hydrophobic substrates without any organic solvents.     

Enantioselective enzymatic acetylation of racemic [4-[4α,6β (E)]]-6-[4,4-bis(4-fluorophenyl)-3-(1-methyl-1H-tetrazol-5-yl)-1,3-butadienyl]-tetrahydro-4-hydroxy-2H-pyran-2-one

Summary A chiral compound [4R-[4,6ß(E)]]-6-[4,4-bis(4-fluorophenyl)-3-(1-methyl-1H-tetrazol-5-yl)-1,3-butadienyl]-tetrahydro-4-hydroxy-2H-pyran-2-one (R-(+)-1) was prepared by the lipase-catalysed stereoselective acetylation of racemic 1 in an organic solvent. Chiral R-(+)-1 is a hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase inhibitor and a potential anticholesterol drug candidate. Among various lipases evaluated, lipase PS-30 from Pseudomonas species efficiently catalysed acetylation of the undesired enantiomer of racemic 1 to yield the S-(–)-acetylated product 2 and unreacted desired R-(+)-1. A reaction yield of 48 mol% and an optical purity of 98% were obtained for R-(+)-1 when the reaction was conducted in toluence as solvent in the presence of isopropenyl acetate as acyl donor. Lipase PS-30 was immobilized on Accurel polypropylene (PP) and the immobilized enzyme was reused (five cycles) in the acetylation reaction without loss of enzyme activity, productivity, or optical purity of the R-(+)-1. The enzymatic acetylation process was scaled-up to 501 and a 640-l volume (preparative batches) at a substrate concentration of 4 g/l. R-(+)–1 was recovered from the preparative batches in 68–71% recovery yield with 98.5% gas chromatography homogeneity index and 98.5% optical purity. The S-(–) acetate 2 produced by the acetylation reaction was enzymatically hydrolysed by lipase PS-30 in a biphasic system to prepare the corresponding S-(–)-1.Correspondence to: R. N. Patel     

Determination of the optical purity of threonine and hydroxyproline by capillary gas chromatography on a chiral stationary phase

Summary Experimental conditions for the derivatization and resolution by GLC of all stereoisomers of threonine and 4-hydroxyproline are reported. Threonine was in two steps converted toN,O-bisisobutoxycarbonyl 2,2,2-trifluoroethyl ester derivatives, the second of which was performed under anhydrous conditions. As such the enantiomers could pairwise be separated by capillary gas chromatography on a Chirasil-Val column. SinceL- andD-threonine eluted much earlier than the corresponding allo forms, quantitative determination of the allothreonine content inD- orL-threonine down to the one percent level could be simply accomplished but also enantiomeric impurities could be determined. Unlike for threonine, the corresponding 4-hydroxyproline isomers could not all be resolved asN,O-bisisobutoxycarbonyl 2,2,2-trifluoroethyl esters on this column. Although diastereomers could still be separated, the allo pair cochromatographed and the resolution for theL- andD-isomers was low. Complete separation of the 4-hydroxyproline isomers could be accomplished asN,O-bisprotected isobutyl amides, the formation of which required three derivatization steps. These were used for the determination of allohydroxyproline.     

Heterocycles 32. Efficient kinetic resolution of 1-(2-arylthiazol-4-yl)ethanols and their acetates using lipase B from Candida antarctica

In this paper we describe the chemoenzymatic synthesis of new enantiomerically enriched (R)- and (S)-1-(2-arylthiazol-4-yl)ethanols and their acetates by enzymatic enantioselective acetylation of the racemic alcohols rac-2a–d and by methanolysis of the corresponding racemic esters rac-3a–d mediated by lipase B from Candida antarctica (CaL-B) in non-aqueous media. In terms of stereoselectivity and activity, both procedures, acylation and alcoholysis, gave similar good results (50% conversion, E ≫ 200). The absolute configuration of the kinetic resolution products was determined by a detailed ¹H NMR study of the Mosher's derivatives of (S)-2b.     

Synthesis of 2-amino-6-(4-[11C]methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester as a novel potential PET gene reporter probe for HBV and HSV-tk in cancers

Acyclic nucleoside 2-amino-6-(4-methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (ABE, 1) is a new hepatitis B virus (HBV) specific antiviral reagent and shows high anti-HBV activity. Carbon-11 labeled ABE may serve as a novel reporter probe for positron emission tomography (PET) to image HBV and herpes simplex virus thymidine kinase (HSV-tk) in cancers. The radiolabeling precursors 2-amino-6-(4-hydroxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (10) and 2-N-Boc protected analogue 2-N-bis(Boc)amino-6-(4-hydroxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester (12), and the reference standard ABE were synthesized from bis(trifluoroethyl) (2-iodoethoxy)methylphosphonate (5), guanine (6), and 2-amino-6-chloropurine (8). The target radiotracer 2-amino-6-(4-[11C]methoxyphenylthio)-9-[2-(phosphonomethoxy)ethyl]purine bis(2,2,2-trifluoroethyl) ester ([11C]ABE, [11C]1) was prepared by O-[11C]methylation of the unprotected HO-precursor 10, or 2-N-Boc protected HO-precursor 12 with [11C]methyl triflate followed by a quick deprotection reaction, and isolated by solid-phase extraction (SPE) purification in 40-55% radiochemical yields.     

Design,Synthesis, and Insecticidal Activities of Novel meta-Diamide Compounds Containing Ethyl Acetate and Their Derivatives

In this study, a series of meta-diamide compounds containing ethyl acetate group and their derivatives were designed and synthesized. Their insecticidal activities against Plutella xylostella, Spodoptera frugiperda and Alfalfa sprouts were evaluated. Preliminary bioassays showed that some of the title compounds exhibited excellent insecticidal activities. Especially compound ethyl N-(3-((2-bromo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)-2-fluorophenyl)-N-(4-cyanobenzoyl)glycinate and ethyl N-(3-((2-bromo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)-2-fluorophenyl)-N-(6-fluoronicotinoyl)glycinate showed 100 % mortality at 0.1 mg/L against Plutella xylostella and Spodoptera frugiperda, same to broflanilide. Their LC₅₀ against Plutella xylostella is 0.286 mg/L and 0.0218 mg/L, respectively. Moreover, compound ethyl N-(3-((2-bromo-4-(perfluoropropan-2-yl)-6-(trifluoromethyl)phenyl)carbamoyl)-2-fluorophenyl)-N-(6-fluoronicotinoyl)glycinate displayed faster control efficacy than broflanilide at 0.1 mg/L. The results indicated that meta-diamide compounds containing ethyl acetate group could be developed as novel and promising insecticides.     

Synthesis of (2S,2’R,3R,4E,8E)-N-2’-Hydroxyoctadecanoyl-1-O-(β-d-glucopyranosyl)-9-methyl-4,8-sphingadienine (Pen III), a Cerebroside Isolated from Penicillium funiculosum as the Fruiting Inducer against Schizophyllum commune

(2S,2’R,3R,4E,8E)-N-2’-Hydroxyoctadecanoyl-1-O-(β-d-glucopyranosyl)-9-methyl-4,8-sphingadienine (Pen III), a cerebroside isolated from Penicillium funiculosum A-1 as the fruiting inducer against Basidiomycete Schizophyllum commune, was synthesized by starting from d-glucose, l-serine, homoprenyl acetate and stearic acid.     

A New Phosphorylating Agent,Di(2,2,2-Trifluoroethyl) Trimethylsilyl Phosphite. Its Application in Dna Synthesis by The Phosphotriester Approach

Abstract

A new phosphorylating agent, di(2,2,2-trifluoro-ethyl) trimethylsilyl phosphite, has been prepared and is proved to be a useful agent for the phosphorylation of the 3′-hydroxyl group of deoxyribonucleosides in the absence of coupling agents. The resulting deoxyribonucleoside 3′-(2,2,2-trifluoroethyl) phosphates are key intermediates for the synthesis of deoxyribooligonucleotides by the phospho-triester approach.