Search

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]

[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]

(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]

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]

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]

• We heterologous expressed and characterized a novel borneol dehydrogenase from Arabidopsis lyrate in E. coli BL21 (DE3). • The AlBDH coupled with glucose dehydrogenase (GDH) of coenzyme regeneration can efficiently convert rac -camphor to borneol. • A single point mutation L205F could successfully be used for enzymatic resolution of 2 mM rac -camphor, yielding 95.9% of (+)-camphor with an ee s of > 99%. Arabidopsis has attracted increasing attention to biotechnology as a model plant. Among, many of studies have focused on monoterpenoids metabolism. Borneol is a typical representative of monoterpenoids and widely applied in fragrances and pharmaceuticals. And (+)-camphor also is also attracting more and more interest in the field of pharmaceutical. However, the enzyme involved the conversion of borneol and camphor in Arabidopsis is still unknown. In this study, a borneol dehydrogenase (BDH) from Arabidopsis lyrate was overexpressed in Escherichia coli BL21 (DE3). The optimum pH for reduction and oxidation were 7.5 and 9.0, respectively, and the optimum temperature was 45 ℃. The specific activity of reduction reaction for (-)-camphor and (+)-camphor were 1.09 and 0.76 U·mg−1 which were the highest so far. The AlBDH coupled with glucose dehydrogenase (GDH) of coenzyme regeneration could efficiently convert rac -camphor, yielding 4.64 mM rac -borneol within 3.5 h with a conversion of 92.8%. A single point mutation L205F could successfully be used for enzymatic resolution of 2 mM rac -camphor, yielding 95.9% of (+)-camphor with an ee s of > 99%. It also could respectively reduce (+)-camphor and (-)-camphor to optically pure (+)-borneol and (+)-isoborneol. The study of the enzymatic properties of AlBDH lay an important foundation for further studies on the conversion of borneol and camphor in Arabidopsis and provide potential industrial application value for the optically pure enantiomers borneol sustainable synthesis in the future. A novel borneol dehydrogenase from Arabidopsis lyrate for recombinant expression, characterization, exploring active site and application. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] An efficient synthesis for a new conformationally locked chiral cis -1,2-diaminocyclohexane scaffold has been developed. The conformational lock allows for convenient symmetrical derivatization of the amino groups through the reductive amination strategy. A series of optically pure chiral ligands based on the cis -DACH scaffold has been generated to demonstrate a proof-of-concept for these ligands as chiral catalysts in the asymmetric Henry reaction. Excellent yields with moderate enantioselectivity were demonstrated at room temperature, with an increase in enantioselectivity at lower temperatures, showing the potential of this new type of cis -DACH ligand. [ABSTRACT FROM AUTHOR]

d -Pantoic acid (D-PA) is an essential intermediate for the production of d -pantolactone. Here, three d -lactonohydrolases (D -Lacs), namely, Fm -Lac from Fusarium moniliforme SW-902, Fp -Lac from Fusarium proliferatum Nirenberg ECU2002, and Fo -Lac from Fusarium oxysporum AKU3702 were heterogeneously expressed in Pichia pastoris. The constructed recombinant strains produced D -Lacs of 1263 U/mL, 1025 U/mL, and 948 U/mL in a 3-L fermenter, respectively. Simultaneously, these three D -Lacs were used to resolve racemic pantolactone (DL-PL), the hydrolysis rate by Fo -Lac over 40% and the enantiomeric excesses was 99% after 4 h reaction, which outperformed Fm -Lac and Fp -Lac. Under the 800 mL scale reaction, the hydrolysis rate of DL-PL reached 39.2% with a D -PA concentration of 144.6 g/L and space-time yield of 36.2 g/L/h correspondingly. This is the highest catalytic efficiency reported so far, which shows that D -Lac heterologously expressed by P. pastoris has excellent industrial application prospects. • D -Lac was successfully expressed in Pichia pastoris for the first time. • The production of D -Lac by the recombinant P. pastoris is as high as 1000 U/mL or more. • The space-time yield of D -PA production reached 36.2 g/L/h, which is currently the highest in the resolution of DL-PL. [ABSTRACT FROM AUTHOR]