Oxidoreductases and Hydroxynitrilase Lyases: Complementary Enzymatic Technologies for Chiral Alcohols

Biocatalytic processes are useful methods for the production of chiral intermediates. As an example, alcohol dehydrogenases are applied for the production of chiral alcohols by asymmetric reduction of prochiral ketones. From this class of enzymes alcohol dehydrogenase from Lactobacillus brevis will be described with respect to its industrial application. The process for the production of methyl (R)‐3‐hydroxybutyrate using this enzyme is discussed in more detail. The application of alcohol dehydrogenases can be limited by the commercial availability of the starting material as, for instance, in the case of the synthesis of chiral α‐hydroxy acids. For these products asymmetric addition of hydrocyanic acid to aldehydes catalyzed by hydroxynitrile lyases such as (S)‐oxynitrilase from Manihot esculenta is a complementary approach. Also, this enzyme will be characterized in more detail with respect to its industrial production and application.     

Electroenzymatic Synthesis of Chiral Sulfoxides

Chloroperoxidase (CPO) from Caldariomyces fumago (E.C. 1.11.1.10) is able to enantioselectively oxidize various sulfides to the corresponding (R)‐enantiomer of the sulfoxides. For these oxidations the enzyme requires an oxidant. Most commonly, tert‐butyl hydroperoxide (TBHP) and hydrogen peroxide are used. As it is known that these oxidants inactivate the enzyme, the enzymatic reaction was combined with the electrochemical in situ generation of hydrogen peroxide. As substrates for this combination of an enzymatic and an electrochemical reaction methyl p‐tolyl sulfide, 1‐methoxy‐4‐(methylthio)benzene and N‐MOC‐L ‐methionine methyl ester were used to carry out batch experiments.     

假丝酵母C-5的不对称生物还原作用研究

生命与手性密切相关,凡涉及到生命现象和生理活性物质几乎都离不开有关分子的空间立体构型问题,不同构型的手性分子具有不同的生理活性。利用酶反应的立体专一性,用生物转化法取代部分传统的化学方法,可以很方便地制备具有所需手性中心的化合物。因此,近年来生物转化...     

Theoretical Modeling of Surface Confined Chiral Nanoporous Networks: Cruciform Molecules as Versatile Building Blocks

Patterning of solid surfaces with functional organic molecules has been a convenient route to fabricate two‐dimensional materials with programmed architecture and activities. One example is the chiral nanoporous networks that can be created via controlled self‐assembly of star‐shaped molecules under 2D confinement. In this contribution we use computer modeling to predict the formation of molecular networks in adsorbed overlayers comprising cruciform molecular building blocks equipped with discrete interaction centers. To that end, we employ the Monte Carlo simulation method combined with a coarse‐grained representation of the adsorbed molecules which are treated as collections of interconnected segments. The interaction centers within the molecules are represented by active segments whose number and distribution are adjusted. Our particular focus is on those distributions that produce prochiral molecules able to occur in adsorbed configurations being mirror images of each other (surface enantiomers). We demonstrate that, depending on size, aspect ratio, and intramolecular distribution of active sites, the surface enantiomers can co‐crystallize or segregate into extended homochiral domains with largely diversified nanosized cavities. The insights from our theoretical studies can be helpful in designing 2D chiral porous networks with potential applications in enantioselective adsorption and asymmetric heterogeneous catalysis. Chirality 27:397–404, 2015. © 2015 Wiley Periodicals, Inc.     

Different Strategies for the Synthesis of 2′- O -Aminoethyl Adenosine Building Blocks

The chemical modification of the 2′-O-position of nucleosides proved to be of great importance for the RNA stability. Greater stability of RNA duplexes allows a longer half life in the cell and, therefore, a better effect of RNA Interference. Here we investigated the synthesis of 2′-O-aminoethyl adenosine as a cationic modified building block.     

Rickettsia prowazekii Transports UMP and GMP, but Not CMP, as Building Blocks for RNA Synthesis

Rickettsia prowazekii, the etiological agent of epidemic typhus, is an obligate intracellular bacterium and is apparently unable to synthesize ribonucleotides de novo. Here, we show that as an alternative, isolated, purified R. prowazekii organisms transported exogenous uridyl- and guanylribonucleotides and incorporated these labeled precursors into their RNA in a rifampin-sensitive manner. Transport systems for nucleotides, which we have shown previously and show here are present in rickettsiae, have never been reported in free-living bacteria, and the usual nucleobase and nucleoside transport systems are absent in rickettsiae. There was a clear preference for the monophosphate form of ribonucleotides as the transported substrate. In contrast, rickettsiae did not transport cytidylribonucleotides. The source of rickettsial CTP appears to be the transport of UMP followed by its phosphorylation and the amination of intrarickettsial UTP to CTP by CTP synthetase. A complete schema of nucleotide metabolism in rickettsiae is presented that is based on a combination of biochemical, physiological, and genetic information.     

Building Blocks for Polyamide Nucleic Acids: Facile Synthesis Using Potassium Fluoride Doped Natural Phosphate as Basic Catalyst

Abstract

Potassium fluoride doped natural phosphate, inexpensive and environmentally friendly catalyst, is shown to be an efficient basic catalyst for the N1/N9 alkylation of different nucleobases as synthons for PNAs.     

Building Blocks for Synthesis of Oligoarabinonucleotides: Preparation of Arabinonucleoside H-Phosphonates from Protected Ribonucleosides

Abstract

A straightforward and inexpensive synthesis of arabinonucleoside H-phosphonates has been developed. Arabinonucleosides were synthesised from protected ribonucleosides via 2′-keto derivatives. Reaction conditions have been optimised for compounds bearing labile N-protections. Further protecting group manipulation and phosphonylation gave the required H-phosphonate monomers.     

Chiral resolution and neuroprotective activities of enantiomeric dihydrobenzofuran neolignans from the fruit of Crataegus pinnatifida

Three pairs of enantiomeric dihydrobenzofuran neolignans (1a/1b-3a/3b) including four new compounds (1a/1b and 2a/2b) were isolated from the fruit of Crataegus pinnatifida. Their structures including the absolute configurations were elucidated by extensive spectroscopic analyses and comparison between the experimental measurements of electronic circular dichroism (ECD) and the calculated ECD spectra. Additionally, all the enantiomeric neolignans were investigated for their neuroprotective activities against H₂O₂-induced cell injury in human neuroblastoma SH-SY5Y cells. It was found that enantiomers 1a and 1b displayed different degrees of neuroprotective activities, and the results showed enantioselectivity, in which that 1b exhibited noticeable neuroprotective activity, while its enantiomer 1a only exhibited obvious protective effect at lower concentration. Further study demonstrated that the potential protective activities of compounds appeared to be mediated via suppressing cell apoptosis.     

New Building Blocks for the Preparation of Branched Oligonucleotides

Abstract

New building blocks 2 and 3 were prepared and successfully employed for the synthesis of branched oligonucleotides 5 and 6. The structure of oligomers obtained was confirmed by electrospray ionisation mass spectrometry.     

Facile Synthesis of Orthogonally Protected Optically Pure Keto- and Diketopiperazine Building Blocks for Combinatorial Chemistry

A simple and convenient synthesis of orthogonally protected multi-tethered, optically pure 2-ketopiperazine and 2,5-diketopiperazine scaffolds for Fmoc and Boc combinatorial chemistry was achieved, starting from accessible chiral amino acid precursors, by sequentially utilizing reductive alkylation, dipeptide coupling and ketopiperazine ring formation as key steps. These scaffolds can introduce valuable drug-like properties in three independent directions to any medicinally relevant piperazine-based motif by “around the scaffold” drug optimization. In addition, these building blocks have a wide application scope in managing fast and efficient multi-cyclic optimization processes in the combinatorial chemistry and drug design fields.     

A Helical Polyphenylacetylene Having Amino Alcohol Moieties Without Chiral Side Groups as a Chiral Ligand for the Asymmetric Addition of Diethylzinc to Benzaldehyde

One‐handed helical polyphenylacetylenes having achiral amino alcohol moieties, but no chiral side groups, were synthesized by the helix‐sense‐selective copolymerization of an achiral phenylacetylene having an amino alcohol side group with a phenylacetylene having two hydroxyl groups. Since the resulting helical copolymers were successfully utilized as chiral ligands for the enantioselective alkylation of benzaldehyde with diethylzinc, we can conclude that the main‐chain chirality based on the one‐handed helical conformation is useful for the chiral catalysis of an asymmetric reaction for the first time. The enantioselectivities of the reaction were controlled by the optical purities of the helical polymer ligands. In addition, the polymer ligands could be easily recovered by precipitation after the reaction. Chirality 27:454–458, 2015. © 2015 Wiley Periodicals, Inc.     

Synthesis of 3′,5′-Dithymidylyl-α-hydroxyphosphonate Dimer Building Blocks for Oligonucleotide Synthesis—A New Pro-oliguncleotide

Abstract

The synthesis of the dimer building blocks 1 and 2 and their introduction into (T)₁₅-oligonucleotides is described. The stability against 3′-exonuclease digestion (SVP) as well as the hybridization properties (T_m values) were examined.     

Highly Enantioselective Production of Chiral Secondary Alcohols with Candida zeylanoides as a New Whole Cell Biocatalyst

The increasing demand for biocatalysts in synthesizing enantiomerically pure chiral alcohols results from the outstanding characteristics of biocatalysts in reaction, economic, and ecological issues. Herein, fifteen yeast strains belonging to three food originated yeast species Candida zeylanoides, Pichia fermentans, and Saccharomyces uvarum were tested for their capability for asymmetric reduction of acetophenone to 1‐phenylethanol as biocatalysts. Of these strains, C. zeylanoides P1 showed an effective asymmetric reduction ability. Under optimized conditions, substituted acetophenones were converted to corresponding optically active secondary alcohols in up to 99% enantiomeric excess and at high yields. The preparative scale asymmetric bioreduction of 4‐nitroacetophenone ( 1m ) by C. zeylanoides P1 gave (S)‐1‐(4‐nitrophenyl)ethanol ( 2m ) with 89% yield and > 99% enantiomeric excess. Compound 2m has been obtained in an enantiomerically pure and inexpensive form. Additionally, these results indicate that C. zeylanoides P1 is a promising biocatalyst for the synthesis of chiral alcohols in industry.     

Peptidyl Carbamates: Efficient Synthesis Using N-Fmoc-β-aminoalkoxy Carbonyl Chlorides/Active Pentachlorophenyl Carbonates as Monomeric Building Blocks

A simple protocol for the synthesis of linear peptidylcarbamates employing Fmoc-β-aminoalkoxy carbonyl chlorides is described. The N-Fmoc-β-aminoalkoxy carbonyl chlorides were prepared by the reaction of phosgene or triphosgene with Fmoc-protected β-amino alcohol which were isolated as solids. These oxycarbonyl chlorides were also converted to the corresponding pentachlorophenyl carbonates by reacting with pentachlorophenol. Fmoc-β-aminoalkoxy carbonyl chlorides as well as pentachlorophenol carbonates were successfully used as monomeric building blocks for the synthesis of several peptidyl carbamates.     

Synthesis of Fmoc-Gly-Ile Phosphinic Pseudodipeptide: Residue Specific Conditions for Construction of Matrix Metalloproteinase Inhibitor Building Blocks

The efficient synthesis of an Fmoc-Gly-Ile phosphinic pseudodipeptide was desired as an eventual building block for construction of matrix metalloproteinase inhibitors. A Michael-type addition reaction of bis(trimethylsilyl) phosphonite with the appropriate acrylate generated the pseudodipeptide bond. Additional of adamantyl (Ad) protection by our prior route (reaction of in situ generated phosphinic acid chloride with the sodium salt of adamantanol) was surprisingly inefficient. Adamantyl protection was achieved in high yield by refluxing the phosphinic acid, Ag₂O, and 1-AdBr in chloroform. Subsequently a concise one-pot three-step reaction comprising a double deprotection of the N- and C-termini under catalytic hydrogenation conditions followed by selective protection of the N-terminus with an Fmoc group yielded Fmoc-NHCH₂PO(OAd)CH₂CH(2-butyl)CO₂H in 41?% overall yield. These results indicate that, as the diversity of phosphinic pseudodipeptides is increased to create selective matrix metalloproteinase inhibitors, different synthetic pathways may be required for efficient building block preparation.     

Synthesis of New Pseudonucleosides Containing Chiral Cyclosulfamides as Agycone

Abstract

A series of chiral cyclosufamides have been synthesized in four steps, starting from N-benzoylaminoacids. Regioselective glycosylation of these pseudopyrimidic heterocycles was carried out after deprotection. Best glycosylation results were obtained by preliminary silylation of cyclosulfamides, and their condensation with a tetraacetylribofuranose and pentaacetylglucopyranose is described, which yielded the pseudonucleosides in a β-anomeric configuration.     

Low‐Temperature‐Processed Colloidal Quantum Dots as Building Blocks for Thermoelectrics

Colloidal quantum dots (CQDs) are demonstrated to be promising materials to realize high‐performance thermoelectrics owing to their low thermal conductivity. The most studied CQD films, however, are using long ligands that require high processing and operation temperature (>400 °C) to achieve optimum thermoelectric performance. Here the thermoelectric properties of CQD films cross‐linked using short ligands that allow strong inter‐QD coupling are reported. Using the ligands, p‐type thermoelectric solids are demonstrated with a high Seebeck coefficient and power factor of 400 μV K^?1 and 30 µW m^?1 K^?2, respectively, leading to maximum ZT of 0.02 at a lower measurement temperature (<400 K) and lower processing temperature (<300 °C). These ligands further reduce the annealing temperature to 175 °C, significantly increasing the Seebeck coefficient of the CQD films to 580 μV K^?1. This high Seebeck coefficient with a superior ZT near room temperature compared to previously reported high temperature‐annealed CQD films is ascribed to the smaller grain size, which enables the retainment of quantum confinement and significantly increases the hole effective mass in the films. This study provides a pathway to approach quantum confinement for achieving a high Seebeck coefficient yet strong inter‐QD coupling, which offers a step toward low‐temperature‐processed high‐performance thermoelectric generators.     

Molecular Evidence for Asymmetric Evolution of Sister Duplicated Blocks after Cereal Polyploidy

Polyploidy (genome duplication) is thought to have contributed to the evolution of the eukaryotic genome, but complex genome structures and massive gene loss during evolution has complicated detection of these ancestral duplication events. The major factors determining the fate of duplicated genes are currently unclear, as are the processes by which duplicated genes evolve after polyploidy. Fine-scale analysis between homologous regions may allow us to better understand post-polyploidy evolution. Here, using gene-by-gene and gene-by-genome strategies, we identified the S5 region and four homologous regions within the japonica genome. Additional phylogenomic analyses of the comparable duplicated blocks indicate that four successive duplication events gave rise to these five regions, allowing us to propose a model for this local chromosomal evolution. According to this model, gene loss may play a major role in post-duplication genetic evolution at the segmental level. Moreover, we found molecular evidence that one of the sister duplicated blocks experienced more gene loss and a more rapid evolution subsequent to two recent duplication events. Given that these two recent duplication events were likely involved in polyploidy, this asymmetric evolution (gene loss and gene divergence) may be one possible mechanism accounting for the diploidization at the segmental level. Supplementary material to this paper is available in electronic form at http://dx.doi.org/10.1007/s11103-005-4414-1