Stereoselective reduction of ketones by <Emphasis Type="Italic">Daucus carota</Emphasis> hairy root cultures

Reduction of acetophenone by Daucus carota hairy root cultures afforded (S)-phenylethanol in high yield (96%) and excellent enantiomeric excess (ee ≥ 98%). Aromatic ketones, keto esters, and a simple aliphatic ketone were reduced with good stereoselectivity (ee = 62–98%) and moderate to high chemical yields (25–90%).     

Coconut water (Cocos nucifera L.)—A new biocatalyst system for organic synthesis

A series of aliphatic and aromatic aldehydes and ketones was reduced using plant cell preparations from coconut juice, Cocos nucifera, also called ACC (água-de-coco do Ceará). The reduced products were typically obtained in excellent yields (%) and with very high enantiomeric excess. Esters, amides, and nitrobenzene, yielded acids, amines and an azoxyderivative with satisfactory results.     

Beneficial effects and mechanism of action of Momordica charantia juice in the treatment of streptozotocin-induced diabetes mellitus in rat

This study investigated the beneficial effects and mechanism of action of the juice of Momordica charantia in streptozotocin (STZ)-induced diabetes mellitus in rats. Diabetes mellitus was associated with significant (p < 0.01) time course reductions in body weight, plasma insulin and the number of insulin positive cells per islet and significant (p < 0.01) time course elevation in blood glucose and osmolarity and systolic blood pressure compared to age-matched healthy controls. Oral intake of M. charantia juice by STZ-induced diabetic rats partially reversed all the diabetes-induced effects measured. Daily oral administration of M. charantia juice to STZ-induced diabetic rates significantly (p < 0.01) reduced the Na⁺- and K⁺ -dependent absorptions of glucose by the brush border membrane vesicles of the jejunum compared to the responses obtained in STZ-induced diabetic rat. Either insulin (100 MM) or the fruit juice lyophilised extract (5 g · ml^–1) can stimulate ¹⁴C-D-glucose uptake in L6 myotubes. These effects were completely blocked by wortmannin, an inhibitor of phosphatidylinositol 3-kinase. High concentrations (10–200 g · ml^-1) of M. charantia juice extract inhibited ¹⁴C-D-glucose uptake in L6 myotubes compared to the control response. The effect of M. charantia treatment was also investigated on myelinated fibre abnormalities in the tibial nerve of STZ-induced diabetic and control rats. The results show that diabetes was associated with significant (p < 0.05) reduction in the mean cross-sectional myelinated nerve fibres, axonal area, myelin area and maximal fibre area compared to end controls. Treatment of STZ-induced diabetic rats with M. charantia juice normalised the structural abnormalities of peripheral nerves. The results indicate that M. charantia can exert marked beneficial effects in diabetic rats, and moreover, it can regulate glucose uptake into jejunum membrane brush border vesicles and stimulate glucose uptake into skeletal muscle cells similar to the response obtained with insulin. (Mol Cell Biochem 261: 63–70, 2004)     

Chiral synthesis via organoboranes. 41. The utility of B-chlorodiisopinocampheylborane for a general synthesis of enantiomerically pure drugs

A general approach to the synthesis of enantiomerically pure α-phenyl amino alcohols via the asymmetric reduction of α-phenyl haloalkyl ketones or α-phenyl aminoalkyl ketones with B-chlorodiisopinocampheylborane is described. Using this approach, an improved synthesis of a potential antipsychotic, α-(4-fluorophenyl)-4-(2-pyrimidinyl)-1-piperazinebutanol in ⩾98% ee, and the broncholdilator 1-(2-methoxy-2-phenethyl)-4-(3-hydroxy-3-phenylpropyl)piperazine (eprozinol) in ⩾99% ee is achieved. © 1995 Wiley-Liss, Inc.     

Asymmetric microbial reduction of ethyl and isoprophyl α,1,3-trioxo-2-isoindolinebutyrate

Summary Microorganisms are capable of the asymmetric reduction of various types of ketones. From a limited screening with 103 selected microbial strains two have been chosen which reduce ethyl and isopropyl ,1,3-trioxo-2-isoindolinebutyrate (1a and 1b) stereoselectively. The optically active products ethyl and isopropyl -hydroxy-1,3-dioxo-2-isoindoline butyrate (2a and 2b) are useful precursors of the cerebral insufficiency improver hydroxy-aniracetam. Up to 3% of substrates 1a or 1b can be added in the reaction medium and converted by Candida parapsilosis. The isolated (R)-enantiomers of the product alcohols 2a and 2b show an enantiomeric excess (ee) of 98%–99%. The process was successfully tested on a 200-1 scale, the transformation rate being 0.83 g/1 per day and the yield of isolated product 72%. With Torulopsis magnoliae (S)-enantiomers of the products 2a and 2b were formed with an ee of 97%–99%.Offprint requests to: Hans G. W. Leuenberger     

Highly enantioselective bioreduction of prochiral ketones by stem and germinated plant of Brassica oleracea variety italica

Abstract

An eco-friendly and environmentally benign asymmetric reduction of a broad range of prochiral ketones employing Brassica oleracea variety italica (stems and germinated plant) as a novel biocatalyst was developed. It was found that B. oleracea variety italica could be used effectively for enantioselective bioreduction in aqueous medium with moderate to excellent chemical yield and enantiomeric excess (ee). This process is more efficient and generates less waste than conventional chemical reagents or microorganisms. Both R- and S-configurations were obtained by these asymmetric reactions. The best ee were achieved for pyridine derivatives (92–99%). The ee in germinated plant reactions were significantly higher than those of stem reactions. The low cost and the easy availability of these biocatalysts suggest their possible use for large scale preparations of important chiral alcohols.     

Enzymatic resolution of rac-1,1-dimethyl-1-sila-cyclohexan-2-ol by ester hydrolysis or transesterification using a crude lipase preparation of Candida cylindracea

Summary rac-2-Acetoxy-1,1-dimethyl-1-sila-cyclohexane (rac-2) was synthesized by esterification of rac-1,1-dimethyl-1-sila-cyclohexan-2-ol (rac-1) with acetic anhydride. Enantioselective hydrolysis of rac-2 in aqueous solution, catalysed by a crude lipase preparation of Candida cylindracea (EC 3.1.1.3), led to the formation of (S)-1 (95% ee). Enantioselective transesterification of rac-1 with triacetin in isooctane, catalysed by the same enzyme preparation, yielded (S)-2 (95% ee), which was separated by chromatography from non-reacted (R)-1 (96% ee). Recrystallization led to an improvement of the enantiomeric purity of (R)-1 and (S)-1 up to >98% ee. Thus the enantiomers of rac-1 were prepared (100 mg scale) with high enantiomeric purities by the use of two different types of enzyme-catalysed reaction.     

An efficient dipeptide‐catalyzed direct asymmetric aldol reaction of equimolar reactants in solid media

The direct asymmetric aldol reactions of equivalent molar amounts of aldehydes and ketones were carried out at −20 °C over alkaline Al₂O₃ with 20 mol % of Pro‐Trp as catalyst and 20 mol % of N‐methylmorpholine or 1,4‐diazabicyclo[2.2.2]octane as additive. After simple and environmentally friendly work‐up, moderate to high isolated yields (up to 95%), good diastereoselectivities (>99:1), and enantioselectivities (up to 98% ee) have been achieved for the reactions of different kinds of ketones with various aldehydes. The catalytic system could be reused without decrease of activity by addition of 10 mol % catalyst and base in the catalytic system. Chirality 2010. © 2009 Wiley‐Liss, Inc.     

First evidence of Mespilus germanica L. (medlar) in Roman Switzerland

The Mespilus (medlar) fruit tree, non-native in Europe, is generally believed to have been introduced to central Europe during the Roman occupation of the region. Archaeobotanical remains of medlar are generally rare, resulting in a patchy knowledge of its early distribution. We here report the earliest finds of Mespilus seeds of the 2nd century a.d. in Switzerland, which were discovered in the Roman vicus of Tasgetium in Eschenz. We summarize the archaeobotanical evidence of Mespilus fruit stones in central Europe during Roman times, which indicate a wide geographical distribution of Mespilus. In addition, we give an overview of Roman sources about the use of medlar fruit and glance at medieval evidence.     

Effect of Fruit Juice on Glucose Control and Insulin Sensitivity in Adults: A Meta-Analysis of 12 Randomized Controlled Trials

Background

Diabetes mellitus has become a worldwide health problem. Whether fruit juice is beneficial in glycemic control is still inconclusive. This study aimed to synthesize evidence from randomized controlled trials on fruit juice in relationship to glucose control and insulin sensitivity.

Methods

A strategic literature search of PubMed, EMBASE, and the Cochrane Library (updated to March, 2014) was performed to retrieve the randomized controlled trials that evaluated the effects of fruit juice on glucose control and insulin sensitivity. Study quality was assessed using the Jadad scale. Weighted mean differences were calculated for net changes in the levels of fasting glucose, fasting insulin, hemoglobin A1c (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR) using fixed- or random-effects model. Prespecified subgroup and sensitivity analyses were performed to explore the potential heterogeneity.

Results

Twelve trials comprising a total of 412 subjects were included in the current meta-analysis. The numbers of these studies that reported the data on fasting glucose, fasting insulin, HbA1c and HOMA-IR were 12, 5, 3 and 3, respectively. Fruit juice consumption did not show a significant effect on fasting glucose and insulin concentrations. The net change was 0.79 mg/dL (95% CI: −1.44, 3.02 mg/dL; P = 0.49) for fasting glucose concentrations and −0.74 µIU/ml (95% CI: −2.62, 1.14 µIU/ml; P = 0.44) for fasting insulin concentrations in the fixed-effects model. Subgroup analyses further suggested that the effect of fruit juice on fasting glucose concentrations was not influenced by population region, baseline glucose concentration, duration, type of fruit juice, glycemic index of fruit juice, fruit juice nutrient constitution, total polyphenols dose and Jadad score.

Conclusion

This meta-analysis showed that fruit juice may have no overall effect on fasting glucose and insulin concentrations. More RCTs are warranted to further clarify the association between fruit juice and glycemic control.     

Asymmetric Reduction of Ketones by Biocatalysis Using Clementine Mandarin (Citrus reticulata) Fruit Grown in Annaba or by Ruthenium Catalysis for Access to Both Enantiomers

Biocatalytic reduction of prochiral ketones using freshly ripened clementine mandarin (Citrus reticulata) in aqueous medium is reported. High enantioselectivities were observed, especially for the bioreduction of indanone 3 , tetralone 4 , and thiochromanone 5 with respectively 95%, 99%, and 86% enantiomeric excess (ee). Enantioselective bio‐ and metal‐catalyzed reactions were compared. Chiral ruthenium catalysts afforded good asymmetric inductions (>75% ee) in most cases, enantiomeric excesses depending on the nature of substrate and ligand. N‐aminoindanol prolinamide L³ was revealed as the best ligand for most ketones. Interestingly, for several substrates both enantiomers could be obtained using either Citrus reticulata or ruthenium complex. Chirality 27:205–210, 2015. © 2014 Wiley Periodicals, Inc.     

Lens culinaris: A new biocatalyst for reducing carbonyl and nitro groups

A series of aliphatic and aromatic aldehydes and ketones, as well as some nitrocompounds were reduced using whole plant cells from Lens culinaris seeds. In addition, we also investigated the possibility of enzymatic ester hydrolysis to explore the potential of these seeds. The reduced ketones products were obtained in yields of 8 ∼ 82% and enantiomeric excess of 39 ∼ 75%. Aldehydes were more reactive than ketones with high chemical yield (95→99%), whereas the aromatic nitrocompounds showed low (2%) to high (> 99%) conversion depending upon the nature and position of the aromatic ring substituents. Ester hydrolysis by the Lens culinaris was quite effective with the ester p-nitrophenyl acetate (> 99% conversion).     

Photobiocatalyzed asymmetric reduction of ketones using Chlorella sp. MK201

Aromatic ketones were reduced using suspension culture of Chlorella sp. MK201 under fluorescent light illumination producing the corresponding chiral alcohols in high yields with excellent enantiomeric excess (ee). For example, 2′,3′,4′,5′,6′-pentafluoroacetophenone at 0.25?mg/ml was converted to the corresponding (S)-alcohol in 80?% yield with?>99?% ee by 1?mg dry wt of Chlorella/ml in 12?h illumination (2,000 lux).     

Production of enantiomerically pure (S)-phenyl(pyridin-2-yl)methanol with Lactobacillus paracasei BD101

Abstract

Asymmetric reduction studies of heteroaryl ketones, including phenyl(pyridin-2-yl)methanone in enantioselective form with biocatalysts are very few, and chiral heteroaryl alcohols have been synthesized generally in the small scale. In this study, seven bacterial strains have been used to produce the (S)-phenyl(pyridin-2-yl)methanol in high enantiomeric excess and yield. Among the tested strains, Lactobacillus paracasei BD101, was found to be the best biocatalyst for the reducing phenyl(pyridin-2-yl)methanone to the (S)-phenyl(pyridin-2-yl)methanol at gram scale. The asymmetric bioreduction conditions were systematically optimized using L. paracasei BD101, which demonstrated excellent enantioselectivity and high level of conversion for the bioreduction reaction. (S)-phenyl(pyridin-2-yl)methanol, which is an analgesic, was produced enantiomerically pure form in the first time on gram scale using a biocatalyst. In total, 5.857?g of (S)-phenyl(pyridin-2-yl)methanol in enantiomerically pure form (>99% enantiomeric excess) was obtained in 52?h with 93% yield using whole cells of L. paracasei BD101. Enantiomerically pure (S)-phenyl (pyridin-2-yl)methanol, which is an analgesic, was first produced in the gram scale using a biocatalyst with excellent ee (>99%) and yield (93%).     

Crystal structure and iterative saturation mutagenesis of ChKRED20 for expanded catalytic scope

ChKRED20 is an efficient and robust anti-Prelog ketoreductase that can catalyze the reduction of ketones to chiral alcohols as pharmaceutical intermediates with great industrial potential. To overcome its limitation on the bioreduction of ortho-substituted acetophenone derivatives, the X-ray crystal structure of the apo-enzyme of ChKRED20 was determined at a resolution of 1.85 Å and applied to the molecular modeling and reshaping of the catalytic cavity via three rounds of iterative saturation mutagenesis together with alanine scanning and recombination. The mutant Mut3B was achieved with expanded catalytic scope that covered all the nine substrates tested as compared with two substrates for the wild type. It exhibited 13–20-fold elevated k _cat/K _m values relative to the wild type or to the first gain-of-activity mutant, while retaining excellent stereoselectivity toward seven of the substrates (98–> 99% ee). Another mutant 29G10 displayed complementary selectivity for eight of the ortho-substituted acetophenone derivatives, with six of them delivering excellent stereoselectivity (90–99% ee). Its k _cat/K _m value toward 1-(2-fluorophenyl)ethanone was 5.6-fold of the wild type. The application of Mut3B in elevated substrate concentrations of 50–100 g/l was demonstrated in 50-ml reactions, achieving 75–> 99% conversion and > 99% ee.

     

An efficient protocol for transient transformation of intact fruit and transgene expression inCitrus

In this study, conditions were optimized for transient gene expression in Rough Lemon (Citrus jambhiri Lush.), a major rootstock used in the citrus growing regions of Pakistan.Agrobacterium tumefaciens carrying the binary vector p35GUSINT, containingNPT II andGUS genes, was used in the study. The transformation method was based on injection ofAgrobacterium intoCitrus fruits followed by histochemical assay ofGUS activity in different tissues. Different tissues of mature fruits exhibited significantly different percentages of transientGUS expression: in rind (76%), spongy tissue (92%), juice vesicles (0%) and seeds (83%) (P<0.01)., The incubation period after injecting theAgrobacterium culture also showed a significant (P<0.01) effect on the transient expression ofGUS in these tissues. An incubation period of 48 h was found to be the best (72%) for transformation of whole fruit, followed by 72 h (67%) and 96 h (49%). TransientGUS expression also varied significantly (P<0.01) in juice vesicles and seeds as fruit matured. Juice vesicles from mature fruits showed no transientGUS expression, while those from immature fruits showed 50% expression. Furthermore, transformation of seeds had no effect on their germination capability. Germinating seeds from mature fruits injected withAgrobacterium culture showed tolerance to kanamycin (100 mg/L), which varied with the incubation period (55% at 48 h, 25% at 72 h and 23% at 96 h). This report offers an easy protocol for transient expression studies of transgenes and has the potential to be used for stable transformation ofCitrus.     

Evaluation of noni (Morinda citrifolia L.) juice antiproliferative activity using the Helianthus tuberosus classical in vitro growth model system

Morinda citrifolia L. (noni) is a tropical plant that has been used for centuries in traditional medicine for numerous purposes and, nowadays, is largely commercialised on the worldwide market as a dietary supplement. Long-term in vitro cultures of Helianthus tuberosus dormant parenchyma explants constitute a classical growth model that can be used to evaluate the proliferative or antiproliferative and/or cytotoxic effects of different mixtures of chemicals present in food or with putative pharmacological applications. Explants of dormant tubers were cultured in vitro with 2%, 10% and 20% (v/v) of noni fruit juice. After four weeks of culture, explant cell growth was reduced 40.5%, 72.5% and 73.9%, respectively, by 2%, 10% and 20% (v/v) of noni juice in comparison to untreated controls. Our results demonstrated that noni fruit juice possesses strong antiproliferative capacity, low cytotoxicity and moderate antioxidant activity.     

Quality versus quantity: Foraging decisions in the honeybee (Apis mellifera scutellata) feeding on wildflower nectar and fruit juice

Foraging animals must often decide among resources which vary in quality and quantity. Nectar is a resource that exists along a continuum of quality in terms of sugar concentration and is the primary energy source for bees. Alternative sugar sources exist, including fruit juice, which generally has lower energetic value than nectar. We observed many honeybees (Apis mellifera scutellata) foraging on juice from fallen guava (Psidium guajava) fruit near others foraging on nectar. To investigate whether fruit and nectar offered contrasting benefits of quality and quantity, we compared honeybee foraging performance on P. guajava fruit versus two wildflowers growing within 50 m, Richardia brasiliensis and Tridax procumbens. Bees gained weight significantly faster on fruit, 2.72 mg/min, than on either flower (0.17 and 0.12 mg/min, respectively). However, the crop sugar concentration of fruit foragers was significantly lower than for either flower (12.4% vs. 37.0% and 22.7%, respectively). Fruit foragers also spent the most time handling and the least time flying, suggesting that fruit juice was energetically inexpensive to collect. We interpret honeybee foraging decisions in the context of existing foraging models and consider how nest‐patch distance may be a key factor for central place foragers choosing between resources of contrasting quality and quantity. We also discuss how dilute solutions, such as fruit juice, can help maintain colony sugar–water balance. These results show the benefits of feeding on resources with contrasting quality and quantity and that even low‐quality resources have value.     

Personalized automation of treatment planning in head-neck cancer: A step forward for quality in radiation therapy?

PurposeTo perform a comprehensive dosimetric and clinical evaluation of the new Pinnacle Personalized automated planning system for complex head-and-neck treatments.MethodsFifteen consecutive head-neck patients were enrolled. Radiotherapy was prescribed using VMAT with simultaneous integrated boost strategy. Personalized planning integrates the Feasibility engine able to supply an “a priori” DVH prediction of the achievability of planning goals. Comparison between clinically accepted manually-generated (MP) and automated (AP) plans was performed using dose-volume histograms and a blinded clinical evaluation by two radiation oncologists. Planning time between MP and AP was compared. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 1500 2D-array.ResultsFor similar targets coverage, AP plans reported less irradiation of healthy tissue, with significant dose reduction for spinal cord, brainstem and parotids. On average, the mean dose to parotids and maximal doses to spinal cord and brainstem were reduced by 13–15% (p < 0.001), 9% (p < 0.001) and 16% (p < 0.001), respectively. The integral dose was reduced by 16% (p < 0.001). The dose conformity for the three PTVs was significantly higher with AP plans (p < 0.001). The two oncologists chose AP plans in more than 80% of cases. Overall planning times were reduced to <30 min for automated optimization. All AP plans passed the 3%/2 mm γ-analysis by more than 95%.ConclusionComplex head-neck plans created using Personalized automated engine provided an overall increase of plan quality, in terms of dose conformity and sparing of normal tissues. The Feasibility module allowed OARs dose sparing well beyond the clinical objectives.     

Effect of Fruit Juice on Cholesterol and Blood Pressure in Adults: A Meta-Analysis of 19 Randomized Controlled Trials

Background

The effect of fruit juice on serum cholesterol and blood pressure in humans has generated inconsistent results. We aimed to quantitatively evaluate the effect of fruit juice on serum cholesterol and blood pressure in adults.

Methods

We performed a strategic literature search of PubMed, EMBASE, and the Cochrane Library (updated to October, 2012) for randomized controlled trials that evaluated the effects of fruit juice on serum cholesterol and blood pressure. Study quality was assessed by using the Jadad scale. Weighted mean differences were calculated for net changes in cholesterol and blood pressure by using fixed-effects model. Prespecified subgroup and sensitivity analyses were conducted to explore the potential heterogeneity.

Results

Nineteen trials comprising a total of 618 subjects were included in this meta-analysis. Fruit juice consumption borderlinely reduced the diastolic blood pressure (DBP) by 2.07 mm Hg (95% CI: −3.75, −0.39 mm Hg; p = 0.02), but did not show significant effects on total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) concentrations or systolic blood pressure (SBP) values. A significant reduction of TC concentration was observed in low-median intake of total polyphenols group. Subgroup analyses for HDL-C and LDL-C concentrations did not show statistically significant results. No significant heterogeneity was detected for all the measures.

Conclusion

This meta-analysis suggested that fruit juice had a borderline significant effect on reducing DBP, but had no effect on TC, HDL-C, LDL-C concentrations or SBP.