Synthesis of enantiopure chloroalcohols by enzymatic kinetic resolution

3-Alkenyl and heteroaryl chloroalcohols have been obtained in excellent enantiomeric excess (>99%) by enzymatic kinetic resolution using the haloalcohol dehalogenase HheC. Yields were close to the theoretical maximum for all substrates employed. Furthermore, the applicability of this methodology on multigram scale has been established.     

Synthesis of enantiopure cis-decahydroquinolines from homotyramines by Birch reduction and aminocyclization

Birch reduction of homotyramines with a syn-β-amino alcohol unit followed by acid treatment of formed dihydroanisole derivatives gives polysubstituted enantiopure cis-decahydroquinolines. The stereoselectivity of the process differs if the hydroxyl group is free or protected. The procedure allows the synthesis of 7-oxodecahydroquinolines embodying four stereogenic centres with the same relative configuration as that of lepadins F and G.     

Synthesis of enantiopure bis-isoxazolines from (4R)-(+)-4-acetoxycyclopent-2-enone

(4R)-(+)-4-Acetoxycyclopent-2-enone was used as a starting material in the stereoselective synthesis of enantiopure bis-isoxazolines.     

Purification and Partial Characterization of (6-4) Photoproduct DNA Photolyase from Xenopus laevis

Abstract— The (6-4) photoproduct DNA photolyase was detected in two vertebrate animals Crotalus atrox (rattlesnake) and Xenopus laevis (South African clawed toad). The enzyme was extensively purified from X. laevis and characterized. The highly purified enzyme is fluorescent with an excitation maximum at 420-440 nm and emission maximum at 460-480 nm. The photorepair action spectrum matches the fluoresoence excitation spectrum with a 430 nm maximum.     

Synthesis of new enantiopure trans-3,4-diaminocaranes from (+)-3-carene

A synthetic strategy to obtain new enantiopure trans-3,4-diaminocaranes derived from (+)-3-carene via a stereoselective methodology is described. The stereoselective preparation of 3,4-α-carene- or 3,4-β-carene-epoxide is followed by a ring opening by sodium azide to obtain the azido-alcohols. Subsequent cyclization affords the corresponding aziridine diastereoisomers, which are converted to azido amines by opening of the aziridine rings by sodium azide and then reduced to the final diamine diastereoisomers. The absolute configurations of the final diamines and of novel intermediates are established by ¹H NMR spectra correlated with conformational analysis supported by molecular modeling.     

Synthesis of 4- and 8-methylthienothienopyridines

The synthesis of some new heterocyclic bases is described. These are 4-methylthieno (2,3-b) thieno (2,3-b)-pyridine (I), and 8-methylthieno (3, 2-b) thieno (2,3-b)pyridine (II).     

Structure and relative stability of drum-like C4nN2n n = 3-8) cages and their hydrogenated products C4nH4nN2n (n = 3-8) cages

The drum-like C4nNn (n = 3-8) cages and corresponding hydrogenated products C4n H4nN2n (n = 3-8) are studied at the DFT B3LYP/6-31G** level. Their structures, energies, and vibrational frequencies have been investigated. Comparison of heat of formation reveals that C32N16 with D8h symmetry in the C4nN2n (n = 3-8) series is a promising candidate as high energy density matter. The calculation of the DeltaG and DeltaH for the hydrogenation of C4nN2n (n = 3-8) shows that it is an exothermic reaction at 298 K and the C4nH4nN2n (n = 3-8) species are more stable than C4nN2n (n = 3-8) species. The analysis of molecular orbital and selected bond lengths of N-N and C-C provides another insight about their stability. Combined with the nucleus-independent chemical shifts (NICS) calculation, it is indicated that molecular stability for cage-shaped molecules depends on not only aromatic character but also the cage effect.     

Synthesis of enantiopure 2-C-methyl-D-erythritol 4-phosphate and 2,4-cyclodiphosphate from D-arabitol

[reaction: see text] Two key intermediates of the newly discovered mevalonate-independent pathway for isoprenoid biosynthesis were prepared. Optically pure 2-C-methyl-D-erythritol 4-phosphate and 2,4-cyclodiphosphate were chemically synthesized from D-arabitol using a convenient benzylidene and tert-butyldimethylsilyl protection of polyhydroxylated intermediates. The new scheme offers a straightforward route to analogues and labeled forms.     

Synthesis of enantiopure 4-amino-3-hydroxymethyl-tetrahydroquinolines via an intramolecular nitrone cycloaddition

Enantiopure 4-amino-3-hydroxymethyl-1,2,3,4-tetrahydroquinolines are synthesized by using an intramolecular cycloaddition of chiral nitrones prepared from aldehydes 5 and (R)-α-(hydroxymethyl)benzylhydroxylamine. Reaction times of the nitrone cycloaddition were optimized by activation under MW-assisted conditions. The absolute configuration of the products was determined by X-ray analysis.     

Synthesis of enantiopure 4-hydroxypipecolate and 4-hydroxylysine derivatives from a common 4,6-dioxopiperidinecarboxylate precursor

tert-Butyl 2-substituted 4,6-dioxo-1-piperidinecarboxylates 4 have been prepared in good yield starting from Boc-Asp-O(t)Bu and other beta-amino acids. By analogy with chiral tetramic acids, their reduction by NaBH(4) in CH(2)Cl(2)/AcOH afforded the corresponding cis-4-hydroxy delta-lactams in good yield and stereoselectivity (68-98% de). In the absence of the A(1,3) strain (reduction of 6-substituted 2,4-dioxo-1-piperidines 7), the cis-4-hydroxy isomer was still obtained as the major product but the de values were consistently lower. 4-Hydroxy-6-oxo-1,2-piperidinedicarboxylate 2a, readily accessible from Boc-Asp-O(t)Bu (three steps, 63% overall yield), has proven to be an excellent building block for the synthesis of cis- and trans-4-hydroxypipecolates 17 and 24 (52 and 36% overall yield, respectively) and for the synthesis of a protected 4-hydroxylysine derivative 29 (41% overall yield).     

Synthesis of an enantiopure 2-arylcyclohexanols from prochiral enol acetates by an enantioselective protonation/diastereoselective reduction sequence

The enantioselective protonation with 2-sulfinyl alcohols of lithium enolates of 2-arylcyclohexanones with different substituents on the phenyl group takes place with excellent enantioselectivities (89–99%). Chiral 2-phenylcyclohexanone and 2-arylcyclohexanones carrying electron donor substituents on the aromatic ring are converted into the corresponding trans-2-arylcyclohexanols by diastereoselective reduction with sodium naphthalenide in the presence of acetamide. The stereochemical integrity of the tertiary stereocenter is fully preserved using this reduction procedure. Interestingly, the chiral proton source is not consumed in the synthesis.     

Selective catalytic reduction of nitrogen oxides by C1 C3, and C4 hydrocarbons

Data are given on the activity of catalysts containing polyvalent metals in the reduction of nitrogen monoxide by hydrocarbons (CH₄, C₃H₈-C₄H₁₀, C₃H₆) in excess oxygen. It was established that the catalysts H-mordenite and CeO₂-TiO₂ have the highest activity.Translated from Teoreticheskaya i Éksperimentalnaya Khimiya, Vol. 29, No. 1, pp. 92–94, January–February, 1993.     

Geometries and electronic properties of carbon-nitrogen clusters C8N4 and C8N4+/-

The geometry optimization and frequency analysis for the low-lying electronic states of C(8)N(4) and its ions are performed at the DFT/6-31G(d) level. Their energies are calibrated at the CCSD(T)/6-31G(d) level of theory. Ionization energy, electron affinity, binding energy of C(8)N(4), and anion photoelectron spectra of C(8)N(4)(-) are provided at the CCSD(T)/6-31G(d) level. Mulliken populations, leading configurations, bond orders, and compositions of molecular orbitals are used to examine the bonding characteristics in the low-lying electronic states of C(8)N(4) and its ions. It is surprising to find that the ground state of C(8)N(4) is the open shell (5)A(1) state. Interestingly for the low-lying electronic states of C(8)N(4) and its ions, their structures significantly corrugated, which may be caused by their larger [N]/([N]+[C]) ratios. In addition, the similarities and differences between C(8)N(4) and C(10)N(2)(II) are analyzed and discussed.     

KF/Al_2O_3催化合成8-氯-4-(2-氯-4-氟苯氧基)喹啉

8-氯-4-(2-氯-4-氟苯氧基)喹啉(CCFQ)是DowElanco公司开发的新颖杀菌剂,它具有独特的杀菌机理—抑制与嘧啶生物合成有关的二氢乳清酸酯脱氢酶[1],能防治对现有杀菌剂产生抗性的病原菌,与现有杀菌剂无交互抗性,并且可与多种杀菌剂复配增效.文献[2]合成条件苛刻,原料损失很大,且需色谱分离提纯,收率较低.为解决以上问题,本文以固载氟化钾为催化剂,对4,8-二氯喹啉和2-氯-4-氟苯酚的缩合反应进行研究,发现催化缩合法条件温和,分离方法简单,收率可达75%.ClNCl FOHClKF/Al2O3ClNOClF主要仪器为NICOLET60SXR-FTIR红外光谱仪,KBr压…     

Synthesis of enantiopure axially chiral C3-symmetric tripodal ligands and their application as catalysts in the asymmetric addition of dialkylzinc to aldehydes

The enantioselective synthesis of a novel-type C(3)-symmetric tripodal ligand that is composed of a central mesitylene-derived core and three functionalized, axially chiral biaryl subunits is described. The triol (M,M,M)-3 is a suitable catalyst for the enantioselective addition of dialkylzinc to various aromatic aldehydes with asymmetric inductions of up to 98% ee.     

Synthesis of 3-phenylpyrroles by hydride reduction of 4-hydroxypyrrolidin-2-ones

3-Phenylpyrroles 2 were easily prepared in good yields by hydride reduction of 4-hydroxypyrrolidin-2-ones 1 , which have been prepared in high yields from the photoreaction of N,N-dialkylbenzoylacetamides, with lithium aluminum hydride.     

Discovery and synthesis of new UV-induced intrastrand C(4-8)G and G(8-4)C photolesions

UV irradiation of cellular DNA leads to the formation of a number of defined mutagenic DNA lesions. Here we report the discovery of new intrastrand C(4-8)G and G(8-4)C cross-link lesions in which the C(4) amino group of the cytosine base is covalently linked to the C(8) position of an adjacent dG base. The structure of the novel lesions was clarified by HPLC-MS/MS data for UV-irradiated DNA in combination with chemical synthesis and direct comparison of the synthetic material with irradiated DNA. We also report the ability to generate the lesions directly in DNA with the help of a photoactive precursor that was site-specifically incorporated into DNA. This should enable detailed chemical and biochemical investigations of these lesions.     

Synthesis of enantiopure 3-amino-1-azaspiro[4.5]decan-8-ones by halonium promoted cyclization of amino-tethered cyclohexenes

Haloaminocyclization reactions of polysubstituted γ-aminocyclohexenes give 3-amino-1-azaspiro[4.5]decan-8-one derivatives. The stereocontrol, chemoselectivity (N-attack vs O-attack), and influence of the halonium ion are discussed.     

Synthesis of diastereoisomeric pairs of novel analogues of d4T having an isochroman glycon moiety; their enzymatic kinetic resolution, their enantiopure synthesis, molecular modeling and NMR structural study

An efficient route, starting from 2-bromobenzaldehyde, is described to synthesize racemic diastereoisomeric thymine derivatives of isochroman, which are aromatic analogues of Stavudine, an approved anti-HIV drug. The relative configurations were determined by NOE proton NMR experiments in connection with molecular modeling. Following the separation of the latter diastereoisomers, kinetic resolution was achieved via a transesterification reaction catalyzed by lipases. Using this method, moderate ee's were obtained (0.74-0.98). Thus, an alternative strategy starting from d-mannitol was proposed to provide pure enantiomers. The attribution of absolute configurations was made by chemical filiation on the basis of the configurations obtained from d-mannitol. The structural attributions were confirmed by studying the behavior of proton NMR shifts of the corresponding isochroman Mosher's esters.