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Chiral phenylalanine derivatives are important raw materials and building blocks for the synthesis of peptides and drug molecules. Enantiomerically pure D/L‐3‐pyridyl‐ and phenylalanine has shown wide application potential in the synthesis of various drug intermediates. This article focuses on two synthetic routes from different feedstocks. The first approach is an Erlenmeyer–Plöchl route study using N‐acetylglycine as starting material, whereas the second is an alkylation route study using diethyl acetamidomalonate as starting material. The key step is the resolution of N‐acetamido‐alanine esters using different quantities of fairly inexpensive Protamex proteinase to obtain pure enantiomeric D/L‐3‐pyridyl‐ and substituted phenylalanine or its derivative, with the ee value and purity of all products exceeding 99%. The different chiral arylalanine derivatives that can be prepared using the above two methods have good versatility. [ABSTRACT FROM AUTHOR]

A number of heterocyclic synthons of biologically active compounds were resolved into enantiomers by enzymatic kinetically controlled deracemization in organic media. High enantioselectivities (>98% ee) and good chemical yields were obtained for all substrates using the corresponding lipases. Among the lipases tested, Candida Antarctica B and Burkholderia cepacia were the most efficient enzymes for resoluting these substrates into enantiomers. These compounds were proposed as starting reactants for important bioactive drug preparation that are of interest to many chemists and pharmacologists. 1-Heteroaroethanols are structural fragments of a number of important medical drugs A method was developed that provided high enantiomeric purity of thiochromanols and 4-hydroxythiochromane 1,1-dioxides. The enantiomeric purity of the compounds was determined by derivatization with Mosher acid, as well as NMR in chiral solvating mediums. Absolute configurations were determined using X-ray diffraction analysis and chiral HPLC. [ABSTRACT FROM AUTHOR]

The hydrolase-catalyzed kinetic resolution of fluorinated racemates of 3-arylcarboxylic acids is described. Hydrolysis of ethyl esters of fluorinated acids by esterases and hydrolases in all cases resulted in the formation of hydrolyzed (S)-carboxylic acids and unreacted (R)-esters in high yields and high enantiomeric purity. The influence of separation conditions on the efficiency and enantioselectivity of biocatalytic conversion was also studied. The reactions were carried out under normal conditions (stirring with a magnetic stirrer at room temperature) and microwave irradiation in the presence of hydrolases. Amano PS showed excellent selectivity and good yields in the hydrolysis of fluorinated aromatic compounds. The absolute configuration of the resulting compounds was based on biokinetic studies and the use of chiral HPLC. A molecular modeling of the kinetic resolution of carboxylic acid esters was carried out. [ABSTRACT FROM AUTHOR]

cis-1-amino-2-indanol is an important building block in many areas of chemistry. Indeed, this molecule is currently used as skeleton in many ligands (BOX, PyBOX...), catalysts and chiral auxiliaries. Moreover, it has been incorporated in numerous bioactive structures. The major issues during its synthesis are the control of cis-selectivity, for which various strategies have been devised, and the enantioselectivity of the reaction. This review highlights the various methodologies implemented over the last few decades to access cis-1-amino-2-indanol in racemic and enantioselective manners. In addition, the various substitution patterns on the aromatic ring and their preparations are listed. [ABSTRACT FROM AUTHOR]

In this study, lipase‐catalyzed resolution of N‐acetyl‐DL‐methionine methyl ester (N‐Ac‐DL‐MetOMe) was evaluated. A lipase from Brucella thiophenivorans was prone to exhibit high activity and excellent enantioselectivity toward N‐Ac‐DL‐MetOMe to produce the key chiral intermediate N‐acetyl‐L‐methionine methyl ester (N‐Ac‐L‐MetOMe). The results showed that the enzymatic reaction was carried out in 100 g/L racemic substrate for 2 h, the conversion reached 51.3%, the enantiomeric excess value N‐Ac‐L‐MetOMe exceeded 99%, and the enantiomeric ratio value >200. Therefore, the lipase from B. thiophenivorans has potential prospects for the resolution of N‐Ac‐DL‐MetOMe to produce the important intermediate N‐Ac‐L‐MetOMe. [ABSTRACT FROM AUTHOR]

The optimization of enzymatic process for the resolution of chemically and pharmaceutically important racemic amines is described using a continuous flow bioreactor. Also described are the isolation and purification methods of the reaction products and the various parameters affecting the optimal reaction conditions for the enzymatic resolution to afford the products in high chemical purity and enantiomeric excess (ee) of over 90%. [ABSTRACT FROM AUTHOR]

In the chemical synthesis of L-syn-p-methylsulfoxide phenylserine ethyl ester (D-ethyl ester), l-tartaric acid or enzymatic resolution is employed to resolve the racemate, and thus obtain the target compound, and the remaining isomer can be recycled to obtain the raw material. In this study, high-purity L-syn-p-methylsulfoxide phenylserine (L-syn-MPS) was obtained. The kinetics of the d-threonine aldolase enzymatic hydrolysis reaction reveals that D-syn-p-sulfoxylphenylserine resolves well in [BMIM][BF4] ionic solvents. The D/L-syn-MPS racemate was resolved using a two-phase ionic solvent [BMIM][NTf2] to afford L-syn-MPS (ee (enantiomeric excess) > 99%) and a white solid in 41.7% yield. Therefore, this system is suitable for the separation of insoluble aldehydes and successfully avoids the condensation of hydroxyl aldehydes to form D-anti-MPS.

(−)‐Agelastatin A was synthetized employing a flow photorearrangement of a pyridinium salt, constructing in one step the cyclopentene core possessing the desired functionalities and relative configurations. A flow enzymatic kinetic resolution of the resulting bicyclic vinyl aziridine delivered the enantiopure precursor to the natural product. This total synthesis required the use of a single protective group. Two novel agelastatin N3‐derivatives were synthesized and their cytotoxicity evaluated against a series of cancer cell lines, which corroborated the importance of unsubstituted N3 in the biological activity of (−)‐agelastatin A. [ABSTRACT FROM AUTHOR]

A general chemo-enzymatic approach to synthesize both enantioenriched trans-3-alkoxyamino-4-oxy-2-piperidones, which are important scaffold for various naturally occurring alkaloids, is reported. To this end, a selective transition-metal-free dual C−H oxidation of piperidines mediated by the TEMPO oxoammonium cation (TEMPO+) was used, followed by enzymatic resolution of the corresponding alkoxyamino-2-piperidones with Candida antarctica lipase (CAL-B), to yield the title compounds in high enantiomeric excess (ee). The absolute configuration of both enantioenriched compounds was determined using chemical correlation and circular dichroism (CD) spectroscopy. The former method highlights the oxidative ring contraction of the trans-alkoxyamine-2-piperidone ring into its corresponding 2-pyrrolidinone. [ABSTRACT FROM AUTHOR]

(S)-Phosphonothrixin is a phosphonate natural product produced by Saccharothrix sp. ST-888 that exhibits herbicidal activity. The previously reported asymmetric synthesis of (S)-phosphonothrixin is laborious and difficult to reproduce. In this study, we developed a scalable and concise enantioselective total synthesis of (S)-phosphonothrixin via two different synthetic routes by the enzymatic resolution of a known racemic epoxy alcohol. The second-generation synthesis was more efficient in terms of the overall yield (15%) and the number of steps (7) and afforded a unique cyclic phosphonate (phostone) as the product of the C-P bond formation reaction, which was converted to (S)-cyclic phosphonothrixin. Both (S)-phosphonothrixin and (S)-cyclic phosphonothrixin induced chlorosis in the plant Arabidopsis thaliana. However, (S)-cyclic phosphonothrixin exhibited lower activity than (S)-phosphonothrixin owing to its fixed conformation, as evidenced by a structure-activity relationship study. This study paves the way for the elucidation of the detailed mode of action of (S)-phosphonothrixin. [ABSTRACT FROM AUTHOR]

[Display omitted] • A modified route to (1R,2R) and (1S,2S) 2-hydroxy-cyclobutylamines using easily available N -Cbz-2-amino-cyclobutanone. • Cbz protected (1R,2R) 2-hydroxy-cyclobutylamine was synthesized in 14 % yield over 5 steps. • The Cbz protecting group with ultraviolet absorption provides convenience for separation and detection. (1R,2R) and (1S,2S) 2-hydroxy-cyclobutylamines are important substructures in a range of bio-active molecules and pharmaceutical candidates. In view of the potential safety issues and the low reaction efficiency associated with the earlier published synthetic process, which relies on Curtius rearrangement for the synthesis of 2-amino-cyclobutanone intermediate, a more practical and efficient process to prepare (1R,2R) and (1S,2S) 2-hydroxy-cyclobutylamines using readily available N- Cbz-2-amino-cyclobutanone was developed. Cbz protected (1R,2R) 2-hydroxy-cyclobutylamine could be synthesized in 14 % yield over 5 steps. [ABSTRACT FROM AUTHOR]

A scalable approach to (2R)‐hydroxyoctadec‐3‐enoic acid ((−)‐2) is reported, which is the fatty acid constituent of numerous sphingolipids of biological significance. Key to success was the chemoselective trans‐hydrogenation of a functionalized propargylic alcohol precursor with [Cp*RuCl]4 as the catalyst, followed by lipase‐catalyzed resolution of the racemic product. (−)‐2 then served the shortest total synthesis of the marine natural product symbioramide known to date. [ABSTRACT FROM AUTHOR]

Candida antarctica lipase B-catalyzed hydrolysis of carbocyclic 5–8-membered cis β-amino esters was carried out in green organic media, under solvent-free and ball-milling conditions. In accordance with the high enantioselectivity factor (E > 200) observed in organic media, the preparative-scale resolutions of β-amino esters were performed in tBuOMe at 65 °C. The unreacted β-amino ester enantiomers (1R,2S) and product β-amino acid enantiomers (1S,2R) were obtained with modest to excellent enantiomeric excess (ee) values (ees > 62% and eep > 96%) and in good chemical yields (>25%) in one or two steps. The enantiomers were easily separated by organic solvent/H2O extraction. [ABSTRACT FROM AUTHOR]

The coconut rhinoceros beetle, Oryctes rhinoceros (Linnaeus 1758) (Coleoptera: Scarabaeidae: Dynastinae) (CRB), is endemic to tropical Asia where it damages both coconut and oil palm. A new invasion by CRB occurred on Guam in 2007 and eradication attempts failed using commonly applied Oryctes rhinoceros nudivirus (OrNV) isolates. This and subsequent invasive outbreaks were found to have been caused by a previously unrecognized haplotype, CRB-G, which appeared to be tolerant to OrNV. The male-produced aggregation pheromone of the endemic, susceptible strain of O. rhinoceros (CRB-S) was previously identified as ethyl 4-methyloctanoate. Following reports from growers that commercial lures containing this compound were not attractive to CRB-G, the aim of this work was to identify the pheromone of CRB-G. Initial collections of volatiles from virgin male and female CRB-G adults from the Solomon Islands failed to show any male- or female-specific compounds as candidate pheromone components. Only after five months were significant quantities of ethyl 4-methyloctanoate and 4-methyloctanoic acid produced by males but not by females. No other male-specific compounds could be detected, in particular methyl 4-methyloctanoate, 4-methyl-1-octanol, or 4-methyl-1-octyl acetate, compounds identified in volatiles from some other species of Oryctes. Ethyl 4-methyloctanoate elicited a strong electroantennogram response from both male and female CRB-G, but these other compounds, including 4-methyloctanoic acid, did not. The enantiomers of ethyl 4-methyloctanoate and 4-methyloctanoic acid were conveniently prepared by enzymatic resolution of the commercially-available acid, and the enantiomers of the acid, but not the ester, could be separated by gas chromatography on an enantioselective cyclodextrin phase. Using this approach, both ethyl 4-methyloctanoate and 4-methyloctanoic acid produced by male CRB-G were shown to be exclusively the (R)-enantiomers whereas previous reports had suggested male O. rhinoceros produced the (S)-enantiomers. However, re-examination of the ester and acid produced by male CRB-S from Papua New Guinea showed that these were also the (R)-enantiomers. In field trapping experiments carried out in the Solomon Islands, both racemic and ethyl (R)-4-methyloctanoate were highly attractive to both male and female CRB-G beetles. The (S)-enantiomer and the corresponding acids were only weakly attractive. The addition of racemic 4-methyloctanoic acid to ethyl 4-methyloctanoate did significantly increase attractiveness, but the addition of (R)- or (S)-4-methyloctanoic acid to the corresponding ethyl esters did not. Possible reasons for the difference in assignment of configuration of the components of the CRB pheromone are discussed along with the practical implications of these results. [ABSTRACT FROM AUTHOR]

All four possible stereoisomers of cis- and trans-2-bromo-2,3-dihydro-1H-inden-1-ols, which are important intermediates in the synthesis of biologically active compounds, were synthesized and their configurations were studied by enzymatic kinetic resolution with the application of the Kazlauskas rule, X-ray diffraction analysis, as well as NMR using NOE-NMR and Karplus equation. Biocatalytic kinetic trans-esterification was used for resolution of racemates. Lipases Burkholderia cepacia and Candida Antarctica B (Novozyme 435) were effective as biocatalysts for biocatalytic esterification of 2-bromo-2,3-dihydro-1H-inden-1-ols with isopropylidene acetate. The absolute configurations of (S,S)-, (R,R)-, (S,R)- and (R,S)-stereoisomers of 2-bromo-2,3-dihydro-1H-inden-1-ols were established. [ABSTRACT FROM AUTHOR]

Synthesis and enzymatic resolution of a new class of alicyclic and heterocyclic mandelic acid derivatives was described. The method relied on the preparation of cyanohydrins from the commercially available aldehydes followed by hydrolysis to corresponding racemic hydroxy esters that were used in the resolution with the Amano PS enzyme. An alternative approach was proposed for compounds that were not suitable for this procedure. For the selected examples, synthesis of the corresponding mandelic acid analogs using the subsequent hydrolysis of esters followed by enantiomeric enrichment via recrystallization of the diastereomeric salt was performed. [Display omitted] [ABSTRACT FROM AUTHOR]

Strigolactones are apocarotenoids known as phytohormones and rhizosphere semiochemicals. Orobanchol, originally isolated from red clover, is recognized as one of the representative canonical strigolactones. A considerable number of naturally occurring orobanchol derivatives have been identified so far, and alectrol (orobanchyl acetate), fabacyl acetate, 7-oxoorobanchol, and 7-hydroxyorobanchol are known as orobanchol derivatives that retain its entire carbon skeleton. By combining our original synthetic method for (±)-orobanchol with enzymatic kinetic resolution, we successfully achieved the synthesis of the natural enantiomer of orobanchol and its conversion to naturally occurring orobanchol derivatives such as alectrol and fabacyl acetate. [Display omitted] • The natural enantiomer of orobanchol, a representative canonical strigolactone, was synthesized. • Alectrol and fabacyl acetate, naturally occurring orobanchol derivatives, were also synthesized. • Enzymatic kinetic resolution was employed as the key methodology. • Acid-mediated cascade cyclization was crucial for the preparation of the tricyclic lactone substrate. [ABSTRACT FROM AUTHOR]

Several thousand different terpenoid structures are known so far, and many of them are interesting for applications as pharmaceuticals, flavors, fragrances, biofuels, insecticides, or fine chemical intermediates. One prominent example is camphor, which has been utilized since ancient times in medical applications. Especially (−)-camphor is gaining more and more interest for pharmaceutical applications. Hence, a commercial reliable source is needed. The natural sources for (−)-camphor are limited, and the oxidation of precious (−)-borneol would be too costly. Hence, synthesis of (−)-camphor from renewable alpha-pinene would be an inexpensive alternative. As the currently used route for the conversion of alpha-pinene to camphor produces a mixture of both enantiomers, preferably catalytic methods for the separation of this racemate are demanded to yield enantiopure camphor. Enzymatic kinetic resolution is a sustainable way to solve this challenge but requires suitable enzymes. In this study, the first borneol dehydrogenase from Pseudomonas sp. ATCC 17453, capable of catalyzing the stereoselective reduction of camphor, was examined. By using a targeted enzyme engineering approach, enantioselective enzyme variants were created with E-values > 100. The best variant was used for the enzymatic kinetic resolution of camphor racemate, yielding 79% of (−)-camphor with an ee of > 99%. Key points: • Characterization of a novel borneol dehydrogenase (BDH) from P. putida. • Development of enantioselective BDH variants for the reduction of camphor. • Enzymatic kinetic resolution of camphor with borneol dehydrogenase. [ABSTRACT FROM AUTHOR]

A general and stereoselective synthetic route for C1-C11 polyketide fragment of doliculide has been achieved in an efficient manner. The key reactions of our synthetic route are enzymatic desymmetrization of meso-diol, application of Evans auxiliary to introduce methyl group, Sharpless asymmetric epoxidation and substrate controlled nucleophilic addition reactions. [ABSTRACT FROM AUTHOR]

The use of mechanochemistry to carry out enantioselective reactions has been explored in the last ten years with excellent results. Several chiral organocatalysts and even enzymes have proved to be resistant to milling conditions, which allows for rather efficient enantioselective transformations under ball-milling conditions. The present article reports the first example of a liquid-assisted grinding (LAG) mechanochemical enzymatic resolution of racemic β3-amino esters employing Candida antarctica lipase B (CALB) to afford highly valuable enantioenriched N-benzylated-β3-amino acids in good yields. Furthermore the present protocol is readily scalable.

Furan-2-carboxylic acid was used as a starting material for the synthesis of dehydro-homopilopic acid. Esterification, hydrogenation and enzymatic hydrolysis followed by the reduction of Weinreb amides and a single-step attachment of a 1-methyl-imidazole residue allowed for the concise synthesis of both enantiomers of pilocarpine.

In this study, a newly isolated strain screened from the indoxacarb‐rich agricultural soils, Bacillus cereus WZZ006, has a high stereoselectivity to racemic substrate 5‐chloro‐1‐oxo‐2,3‐dihydro‐2‐hydroxy‐1H‐indene‐2‐carboxylic acid methyl ester. (S)‐5‐chloro‐1‐oxo‐2,3‐dihydro‐2‐hydroxy‐1H‐indene‐2‐carboxylic acid methyl ester was obtained by bio‐enzymatic resolution. After the 36‐hour hydrolysis in 50‐mM racemic substrate under the optimized reaction conditions, the e.e.s was up to 93.0% and the conversion was nearly 53.0% with the E being 35.0. Therefore, B cereus WZZ006 performed high‐level ability to produce (S)‐5‐chloro‐1‐oxo‐2,3‐dihydro‐2‐hydroxy‐1H‐indene‐2‐carboxylic acid methyl ester. This study demonstrates a new biocatalytic process route for preparing the indoxacarb chiral intermediates and provides a theoretical basis for the application of new insecticides in agricultural production. [ABSTRACT FROM AUTHOR]

Three phthalocyanine derivatives were synthesized and characterized: one modified with a racemic mixture of 1-(4-bromophenyl)ethanol and two other macrocycles modified with each one of the enantioenriched isomers (R)-1-(4-bromophenyl)ethanol and (S)-1-(4-bromophenyl)ethanol. The compounds were characterized by 1H-NMR spectroscopy, mass spectrometry, UV-Vis absorption, and excitation and emission spectra. Additionally, partition coefficient values and the quantum yield of the generation of oxygen reactive species were determined. Interestingly, the phthalocyanine containing a (R)-1-(4-bromophenyl)ethoxy moiety showed higher quantum yield of reactive oxygen species generation than other compounds under the same conditions. In addition, the obtained fluorescence microscopy and cell viability results have shown that these phthalocyanines have different interactions with mammary MCF-7 cells. Therefore, our results indicate that the photochemical and biological properties of phthalocyanines with chiral ligands should be evaluated separately for each enantiomeric species.

The first total synthesis of 16‐Methyleicos‐(4E)‐en‐1‐yn‐3‐ol, a bioactive component of the marine sponge Cribrochalina vasculum was achieved by Evans auxiliary methylation followed by resolution of the corresponding racemates using lipase formulation Novozyme 435 and Mosher's ester method. We report the asymmetric syntheses of four diastereomers (1 a‐d) of the natural compound 1 and established the absolute configuration of chiral centers, leading to the revision of the natural product configuration from 3 S to 3 R. The first total synthesis of 16‐Methyleicos‐(4E)‐en‐1‐yn‐3‐ol, a bioactive component of the marine sponge Cribrochalina vasculum was achieved by Evans auxiliary methylation followed by resolution of the corresponding racemates using lipase formulation Novozyme 435 and Mosher's ester method. We report the asymmetric syntheses of four diastereomers (1 a‐d) of the natural compound 1 and established the absolute configuration of chiral centers, leading to the revision of the natural product configuration from 3 S to 3 R. [ABSTRACT FROM AUTHOR]

The evolution route of a pharmaceutically relevant esterase Rh Est1 in the coordinate system of catalytic properties. [Display omitted] • Directed evolution and circular permutation are rationally combined to reengineer esterase Rh Est1. • A key mutation site "G282S" was identified from a directed evolution library starting with a circular permutation variant CP-176. • The beneficial mutation G282S in CP-176, equivalent to G167S in Rh Est1, was introduced back into Rh Est1-M2, improving catalytic efficiency by 80% and T m by nearly 10 ℃. A pharmaceutically relevant esterase, Rh Est1, could catalyze the hydrolysis of (R,S)-ethyl-2,2-dimethyl cyclopropane carboxylate [(R,S)-DmCpCe] with excellent enantioselectivity, producing (S)-(+)-2,2-dimethyl cyclopropane carboxylic acid [(S)-DmCpCa], which is a key chiral building block for the synthesis of Cilastatin. In our previous work, a mutant Rh Est1-M2 was identified with 6.4-fold higher activity than the wild-type. Additionally, the termini of Rh Est1 protein were altered by circular permutation (CP), resulting in a mutant CP-176 which still maintains the catalytic activity of esterase. In this work, to improve the catalytic properties of Rh Est1, the mutant CP-176 was taken as the parent of directed evolution. Consequently, a new mutant designated as CP-M1 (=CP-176 G282S) was identified, indicating 3.2-fold catalytic efficiency enhancement and nearly 7 ℃ improvement in melting temperature (T m) as compared with CP-176. Furthermore, the beneficial mutation "G282S" of CP-M1 was reversely introduced into Rh Est1-M2, generating the best mutant M3 (= Rh Est1-M2 G167S), with 1.8-fold catalytic efficiency improvement and nearly 10 ℃ improvement of T m , as compared with Rh Est1-M2. This is the first report that the circular permutation and random mutagenesis were combined to reshape a protein, affording distinctly improved activity and thermostability. [ABSTRACT FROM AUTHOR]

In the present paper, we describe several pathways employing immobilized lipase from Candida antarctica B (CAL‐B) as biocatalyst to prepare easily both enantiomers of 3‐(1‐hydroxyethyl)phenol. We have applied hydrolysis with Na2CO3 in organic media under mild conditions. The reaction parameters solvent effect, amount of lipase, and Na2CO3 were examined with 3‐(1‐acetoxyethyl)phenyl acetate as substrate. In alkaline hydrolysis, (R)‐3‐(1‐hydroxyethyl)phenol was obtained with ee = 99% and (S)‐(−)‐3‐(1‐acetoxyethyl)phenol with ee = 98% at optimal conversion (c = 50%) and high selectivity (E > 200). Two other deacylation reactions were compared: alcoholysis with MeOH and with NEt3. The acylation of 3‐(1‐hydroxyethyl)phenol with vinyl acetate was also examined. Alkaline hydrolysis gave the best results, while good regioselectivity and enantioselectivity were observed in alcoholysis and acylation reactions. Finally, (S)‐ and (R)‐3‐(1‐hydroxyethyl)phenol (ee > 98%), key intermediates for the synthesis of important drugs, were prepared from the corresponding racemic diacetate through alkaline hydrolysis. [ABSTRACT FROM AUTHOR]

A general method is presented for the preparation of homochiral 3-hydroxy fatty acid nicotinyl ester. The pyridine moiety of the esters strongly moderates the reactivity of the borane. Incomplete conversion, however, was overcome by Lewis acid catalysis. Additionally, his structural element seems to be responsible for an improvement of the enzymatic resolution compared to the respective alkyl esters. The resolved enantiomers will be the basic material for liposome building molecules of different chirality. [ABSTRACT FROM AUTHOR]

Based on bioinformatics analysis, the promiscuous (+)-γ-lactamase activity of an amidase was identified in Rhodococcus erythropolis PR4 and found to be involved in the nitrile hydratase pathway. The amidase is highly enantioselective and can be used in the kinetic resolution of the Vince lactam. The known structure provides a rare insight into the catalytic mechanism of (+)-γ-lactamase with absolute chiral selectivity. This lactamase was cloned, purified, biochemically characterized, and demonstrated to be an ideal catalyst for the preparation of carbocyclic nucleosides of pharmaceutical interest. The chiral selectivity of this enzyme was investigated by molecular docking and site-specific mutagenesis, which provides a foundation for further engineering of these versatile biocatalysts. [ABSTRACT FROM AUTHOR]

We report the asymmetric total synthesis of (+)-blennolide C and (+)-gonytolide C isolated from endophytic fungi. The synthesis involved construction of a spirochromanone with a chiral quaternary carbon by the aldol reaction of o -hydroxyacetophenones and optically active α-oxygenated cyclohexenone, followed by cyclization under acidic conditions. Oxidative cleavage of the alkene moiety of the spirochromanone furnished the chromanone diester. Through treating the diester with a Lewis acid, the first total synthesis of (+)-blennolide C was achieved by deprotecting the oxygen functionality of the diester and simultaneous Dieckmann condensation. Total synthesis of (+)-gonytolide C was also achieved by lactone formation from the deprotected diester. [ABSTRACT FROM AUTHOR]

An enzyme catalyzing the ammonia-lyase reaction for the conversion ofd-erythro-3-hydroxyaspartate to oxaloacetate was purified from the cell-free extract of a soil-isolated bacteriumPseudomonassp. N99. The enzyme exhibited ammonia-lyase activity towardl-threo-3-hydroxyaspartate andd-erythro-3-hydroxyaspartate, but not toward other 3-hydroxyaspartate isomers. The deduced amino acid sequence of the enzyme, which belongs to the serine/threonine dehydratase family, shows similarity to the sequence ofl-threo-3-hydroxyaspartate ammonia-lyase (EC 4.3.1.16) fromPseudomonassp. T62 (74%) andSaccharomyces cerevisiae(64%) and serine racemase fromSchizosaccharomyces pombe(65%). These results suggest that the enzyme is similar tol-threo-3-hydroxyaspartate ammonia-lyase fromPseudomonassp. T62, which does not act ond-erythro-3-hydroxyaspartate. We also then used the recombinant enzyme expressed inEscherichia colito produce optically purel-erythro-3-hydroxyaspartate andd-threo-3-hydroxyaspartate from the correspondingdl-racemic mixtures. The enzymatic resolution reported here is one of the simplest and the first enzymatic method that can be used for obtaining optically purel-erythro-3-hydroxyaspartate. A novel enzyme “d-erythro-3-hydroxyaspartate dehydratase” was applied to optically activel-erythro-3-hydroxyaspartate production. [ABSTRACT FROM PUBLISHER]

The total syntheses of (−)-amphirionin-4 and (+)-amphirionin-4 have been achieved in a convergent and enantioselective manner. The tetrahydrofuranol cores of amphirionin-4 were constructed in optically active form by enzymatic resolution of racemic cis -3-hydroxy-5-methyldihydrofuran-2(3 H )-one. The polyene side chain was efficiently synthesized using Stille coupling. The remote C8-stereocenter was constructed using the Nozaki-Hiyama-Kishi coupling reaction. Detailed 1 H NMR studies of Mosher esters of (−)-amphirionin-4 and (+)-amphirionin-4 were carried out to support the assignment of the absolute configurations of the C-4 and C-8 asymmetric centers of amphirionin-4. [ABSTRACT FROM AUTHOR]

Enantiomerically highly enriched unsaturated β-ketoesters bearing a quaternary stereocenter can be utilized as building blocks for the synthesis of natural occurring terpenes, i. a., trisporic acid and its derivatives. An advanced building block has been synthesized in a short reaction sequence, which involves an oxidative allylic rearrangement initiated by pyridinium dichromate (PDC) as the key step.

This work presents a preliminary screening directed to obtaining optically active glycerol derivatives. It was tested six lipases from different sources as a means for kinetic resolution.

Preparation of (S)-1-chloro-2-octanol and (S)-1-bromo-2-octanol was carried out by the enzymatic hydrolysis of halohydrin palmitates using biocatalysts. Halohydrin palmitates were prepared by various methods from palmitic acid and 1,2-octanediol. A tandem hydrolysis was carried out using lipases from Candida antarctica (Novozym® 435), Rhizomucor miehei (Lipozyme IM), and “resting cells” from a Rhizopus oryzae strain that was not mycotoxigenic. The influence of the enzyme and the reaction medium on the selective hydrolysis of isomeric mixtures of halohydrin esters is described. Novozym® 435 allowed preparation of (S)-1-chloro-2-octanol and (S)-1-bromo-2-octanol after 1–3 h of reaction at 40 °C in [BMIM][PF6].

Enantioselective syntheses of (-)-alloyohimbane and (-)-yohimbane were accomplished in a convergent manner. The key step involves a modified mild protocol for the enantioselective enzymatic desymmetrization of a meso-diacetate. This provides convenient access to an optically active monoacetate in multi-gram quantities and in high enantiomeric purity. This monoacetate was converted to (-)-alloyohimbane. Reductive amination of the derived aldehyde caused isomerization to the trans-product and, ultimately, the formation of (-)-yohimbane. [ABSTRACT FROM AUTHOR]

Starting from dimethyl (±)-2-hydroxy-3-methylenesuccinnate chemoenzymatic collective formal/total synthesis of enantiomerically pure bioactive natural products has been described via the advanced level common precursor (+)-artabotriol. An efficient enzymatic resolution with high enantiomeric purity, selective diester to diol reduction, and requisite dehydrative coupling reactions without any racemization are the significant topographies. [ABSTRACT FROM AUTHOR]

An enzymatic approach has been successfully utilized in the total synthesis of (-)-malyngolide and its C(5)-epimer. The required configuration was established by an enzymatic kinetic resolution and Sharpless asymmetric dihydroxylation. [ABSTRACT FROM AUTHOR]

2-Piperidineethanol (1) and its corresponding N-protected aldehyde (2) were used for the synthesis of several natural and synthetic compounds. The existence of a stereocenter at position 2 of the piperidine skeleton and the presence of an easily-functionalized group, such as the alcohol, set 1 as a valuable starting material for enantioselective synthesis. Herein, are presented both synthetic and enzymatic methods for the resolution of the racemic 1, as well as an overview of synthesized natural products starting from the enantiopure 1. [ABSTRACT FROM AUTHOR]

An aza-analogue of 1,1'-bi-2-naphthol (BINOL, 3), 7-hydroxy- 8-(2-hydroxynaphth-1-yl)quinoline (8-azaBINOL, 2), was prepared in 3 steps and 49% yield from N,N-diethyl O-(7-hydroxy-8-iodoquinolyl) carbamate via Suzuki coupling with 1-naphthylboronic acid followed by Sanford oxidation and saponification. 8-AzaBINOL (2) was resolved into (-)-(aS) and (+)-(aR) atropisomers via enzymatic hydrolysis of its racemic divalerate derivative with bovine pancreas acetone powder. The configurational stability of diol 2 was found to be intermediate to that of 7,7'-dihydroxy-8,8'-biquinolyl (8,8'-diazaBINOL, 1, least stable) and BINOL (3, most stable). Eyring plot analysis of the enantiomerization kinetics of 1, 2, and 3, in DMSO solution revealed activation parameters of H‡ = +27.4, +19.9, +23.2 kcal mol-1, and S‡ = +3.8, -27.9, -25.3 cal mol-1 K-1, respectively. The unique character of H‡ and S‡ values for biquinolyl 1 suggests that the enantiomerization mechanism for 1 is distinct to that for naphthalenes 2 and 3. Monohydroxy analogues of 2, 7-hydroxy-8-(naphth-1-yl)quinoline (7) and 8-(2- hydroxynaphth-1-yl)quinoline (8), were similarly prepared and their racemization half-lives at room temperature were determined; t1/2(rac) was strongly dependent on solvent for naphthol 8 [t1/2(rac) at 24 °C: in CHCl3 = 2.7 h, in MeOH = 89 h] but not for the quinol 7 [T1/2(rac) at 24 °C: in CHCl3 = 106 h, in MeOH = 120 h]. [ABSTRACT FROM AUTHOR]

Optically pure orthogonally protected trans -3-amino-4-hydroxypiperidines have been easily prepared from (±)-1-benzyl-3,4-epoxypiperidine. The key steps are a regioselective epoxide ring-opening with diallylamine and the enzymatic resolution of the resulting aminoalcohol. It is remarkable the high enantioselectivity obtained with Candida antarctica lipase B in the acetylation of (±)- trans -1-benzyl-3-(diallylamino)-4-hydroxypiperidine. The versatility of the protecting groups is showed in the subsequent transformations performed in relation to the assignment of the absolute configuration of the products. [ABSTRACT FROM AUTHOR]

The enantiomers of 2-azabicyclo[2.2.1]hept-5-en-3-one (γ-lactam) are key chiral synthons in the synthesis of antiviral drugs such as carbovir and abacavir. (+)-γ-Lactamase can be used as a catalyst in the enzymatic preparation of optically pure (−)-γ-lactam. Here, a (+)-γ-lactamase discovered from Bradyrhizobium japonicum USDA 6 by sequence-structure guided genome mining was cloned, purified and characterized. The enzyme possesses a significant catalytic activity towards γ-lactam. The active site of the (+)-γ-lactamase was studied by homologous modeling and molecular docking, and the accuracy of the prediction was confirmed by site-specific mutagenesis. The (+)-γ-lactamase reveals the great practical potential as an enzymatic method for the efficient production of carbocyclic nucleosides of pharmaceutical interest. [ABSTRACT FROM AUTHOR]

Three phthalocyanine derivatives were synthesized and characterized: one modified with a racemic mixture of 1-(4-bromophenyl)ethanol and two other macrocycles modified with each one of the enantioenriched isomers (R)-1-(4-bromophenyl)ethanol and (S)-1-(4-bromophenyl)ethanol. The compounds were characterized by 1H-NMR spectroscopy, mass spectrometry, UV-Vis absorption, and excitation and emission spectra. Additionally, partition coefficient values and the quantum yield of the generation of oxygen reactive species were determined. Interestingly, the phthalocyanine containing a (R)-1-(4-bromophenyl)ethoxy moiety showed higher quantum yield of reactive oxygen species generation than other compounds under the same conditions. In addition, the obtained fluorescence microscopy and cell viability results have shown that these phthalocyanines have different interactions with mammary MCF-7 cells. Therefore, our results indicate that the photochemical and biological properties of phthalocyanines with chiral ligands should be evaluated separately for each enantiomeric species. [ABSTRACT FROM AUTHOR]

A new esterase gene abmbh, encoding a benzoate hydrolase which can enantioselectively hydrolyze l-menthyl benzoate to l-menthol, was recently identified from the genomic library of a soil isolate Acinetobacter sp. ECU2040. The abmbh gene contains a 1080-bp open reading frame encoding a protein of 360 amino acids with a calculated molecular mass of 40.7 kDa. The corresponding enzyme AbMBH was functionally expressed in Escherichia coli BL21 (DE3), purified, and characterized. The AbMBH displayed the maximum activity towards p-nitrophenyl butyrate at 50 °C, and an optimum pH of 8.5. A K of 2.6 mM and a k of 0.26 s were observed towards dl-menthyl benzoate. The AbMBH exhibited a moderate enantioselectivity ( E = 27.5) towards dl-menthyl benzoate. It can also catalyze the enantioselective hydrolysis of a variety of racemic menthyl esters, including dl-menthyl acetate, dl-menthyl chloroacetate, and dl-menthyl butyrate. [ABSTRACT FROM AUTHOR]