Selective synthesis of cerebrosides: (2S, 3R, 4E)-1-O-β-d-galactopyranosyl-N-(2′R and 2′S)-2′-hydroxytetracosanoyl-sphingenine

The cerebrosides were first isolated by Thudicum in 1874 and the structures were established by Carteret al. in 1950 (for review, see [2]). In 1961 Shapiro and Flowers [3] reported the first total synthesis of a cerebroside1 (Fig. 1) which was identified with the natural sample, only through comparison of their i.r. data. In order to confirm the absolute configuration at C-2 of natural cerebroside1, we describe here an unambiguous synthesis of two stereoisomeric cerebrosides1 and2, and found that the¹H-NMR spectra of the synthetic1 (Fig. 2) was completely identical with that of the natural cerebroside reported recently by Dabrowskiet al. [4].In planning the synthetic route, the target structures1 and2 were disconnected at the dotted lines to give three key synthetic intermediates3, 4 and5 or6 (Fig. 1).Abbreviations Bu butyl - Ph phenyl - t-BuPh₂SiCl t-butyldiphenylsilyl chloride - MTPA -methoxy--trifluoromethylphenylacetic acid - THF tetrahydrofuran Part 36 in the series Synthetic Studies on Cell-surface Glycans, for part 35, see [1]     

Total synthesis of cerebrosides: (2S, 3R, 4E)-1-O-β-d-galactopyranosyl-N-(2′R and 2′S)-2′-hydroxytetracosanoylsphingenine

Total syntheses of both (2S, 3R, 4E)-1-O-β-d-galactopyranosyl-N-(2′R)-2′-hydroxytetracosanoylsphingenine 23 and the (2′S) stereoisomer were performed in an unambiguous way by employing either (2S, 3R, 4E)-N-(2′R)-2′-(tert-butyl-diphenylsilyloxy)tetracosanoylsphingenine or its (2′S) stereoisomer as the key glycosyl acceptors. The synthetic cerebroside 23 was shown to be identical with the natural product through comparison of their 400-MHz, ¹H-n.m.r. spectra, thus providing synthetic evidence for the 2′R configuration of the natural cerebroside.     

Metabolism of (2Z,4E)-γ-Ionylideneethanol and (2Z,4E)-γ-Ionylideneacetic Acid in Cercospora cruenta

[2–¹⁴C]-(2Z,4E)-γ-Ionylideneethanol and [2–¹⁴C]-(2Z,4E)-γ-ionylideneacetic acid were converted by Cercospora cruenta to [2–¹⁴C]-(2Z,4E)-1′,4′-dihydroxy-γ-ionylideneacetic acid and [2-¹⁴C]-(2Z,4E)-4′-hydroxy-γ-ionylideneacetic acid, which are intermediates of ABA biosynthesis in C. cruenta.     

4-[(R,S)-1-氨基(2’,4’-二甲氧苄基)]苯氧乙酸的合成

合成了４－［（Ｒ,Ｓ）－１－氨基（２’,４’－二甲氧苄基）］苯氧乙酸以及４个中间体,其结构分别通过红外光谱、核磁共振、折光率、熔点等测试手段得到确证。     

2′-(E)-O-p-coumaroylgalactaric acid and 2′-(E)-O-feruloylgalactaric acid in citrus

2′-(E)-O-p-Coumaroyl- and 2′-(E)-O-feruloylgalactaric acids, hitherto unknown in nature, have been isolated and identified from orange peel.     

A novel vanadium(V) homocitrate complex: synthesis,structure, and biological relevance of [K2(H2O)5][(VO2)2(R,S-homocitrate)2]·H2O

Initial investigations into the possible roles of homocitric acid in the biosynthesis and function of the active site cofactor of nitrogenase resulted in the isolation and characterization of the dinuclear vanadium(V) species [K₂(H₂O)₅][(VO₂)₂(R,S-C₇H₈O₇)₂]·H₂O ( 1). Complex 1 represents the first synthetic structurally characterized transition metal homocitrate complex and may represent an early mobilized precursor in the biosynthesis of VFeco. Compound 1 was characterized by a variety of physical methods, including X-ray crystallography. Crystal data: space group P?* (#2), with a?=?10.292 (3)?Å, b?=?16.663 (3)?Å, c?=?8.343 (1)?Å, α?=?95.93 (1)°, β?=?105.74 (2)°, γ?=?90.86 (2)°, V?=?1386 (1)?ų, and Z?=?2. The homocitrate ligand is coordinated to the vanadium(V) atoms in a bidentate fashion via the deprotonated bridging hydroxyl group and a carboxylate donor. This unique coordination mode accurately mimics the coordination of homocitrate to the cofactor of nitrogenase.     

A cold active (2R,3R)-(−)-di-O-benzoyl-tartrate hydrolyzing esterase from Rhodotorula mucilaginosa

In a screening procedure a pink-colored yeast was isolated from enrichment cultures with (2R,3R)-(−)-di-O-benzoyl-tartrate (benzoyl-tartrate) as the sole carbon source. The organism saar1 was identified by morphological, physiological, and 18S ribosomal DNA/internal transcribed spacer analysis as Rhodotorula mucilaginosa, a basidiomycetous yeast. During growth the yeast hydrolyzed the dibenzoyl ester stoichiometrically to the monoester using the separated benzoate as the growth substrate, before the monoester was further cleaved into benzoate and tartrate, which were both metabolized. The corresponding benzoyl esterase was purified from the culture supernatant and characterized as a monomeric glycosylated 86-kDa protein with an optimum pH of 7.5 and an optimum temperature of 45 °C. At 0 °C the esterase still exhibited 20% of the corresponding activity at 30 °C, which correlates it to psychrophilic enzymes. The esterase could hydrolyze short chain p-nitrophenyl-alkyl esters and several benzoyl esters like benzoyl-methyl ester, ethylene-glycol-dibenzoyl ester, phenyl-benzoyl ester, cocaine, and 1,5-anhydro-d-fructose-tribenzoyl ester. However feruloyl-ethyl ester was not hydrolyzed. The activity characteristics let the enzyme appear as a promising tool for synthesis of benzoylated compounds for pharmaceutical, cosmetic, or fine chemical applications, even at low temperatures.     

Chiroptical properties of diastereomeric five-coordinate Pt(II)–olefin complexes. Molecular structure of [PtCl2{(S,S)-(E)-CNCHCHCN}(R,R)-{C6H5CH(CH3)N(CH3)CH2}2]·C6H6

The chiroptical properties of five-coordinate diastereomeric complexes of general formula [PtCl₂(R,R)-{C₆H₅CH(CH₃)N(CH₃)CH₂}₂{olefin}], with olefin ligands having electron-withdrawing substituents, have been investigated. The sign of CD bands in the 28 000–30 000 cm⁻¹ region appears to be correlated to the absolute configuration of the prochiral coordinated alkene. Single-crystal X-ray diffraction structure determination has been performed on the single diastereomer [PtCl₂(E-but-2-enedinitrile)(R,R)-{C₆H₅CH(CH₃)N(CH₃)CH₂}₂]· C₆H₆. The compound crystallizes in the monoclinic space group C2 with a = 17.842(2), b = 8.466(1), c = 10.464(1) Å, β = 109.34(1)°, Z = 2. The number of observed reflections was 1943 and the final R and R_w values were 0.020 and 0.028 respectively. Trigonal-bipyramidal geometry is observed around the Pt atom, with the two Cl atoms in axial positions. The unsaturated ligand lies in the equatorial plane disclosing S,S absolute configuration.     

Karyological and serological studies in Rana lessonae,R. ridibunda and in their hybrid R. ‘esculenta’ (Amphibia,Anura)

The karyotypes of the three water frog forms: Rana lessonae, R. ridibunda and R. esculenta were analysed from bone marrow cell preparations of animals captured in several localities of the GDR. In the three forms chromosome morphology was similar (5 large and 8 small pairs), although differences in the relative length of most elements were found; R. esculenta chromosomes were always intermediate.One of the small pairs (Chr. 12) was found to be metacentric in R. lessonae and submetacentric in R. ridibunda. Most R. esculenta individuals examined had one meta-and one submetacentric 12th element, indicating the hybrid nature of this form. However 16.6% esculenta proved to be homozygous for either the metacentric or the submetacentric chromosome 12, while 13% lessonae individuals and 7.7% ridibunda were heterozygous for this element.By starch gel electrophoresis an analysis was undertaken of serum proteins from water frogs coming from regions in which the forms occur together (sympatric populations) and from zones in which only one of them lives (allopatric populations).In Rana lessonae, where only one allele had been previously described, two different alleles were found in animals coming from the GDR.If genetic polymorphism is excluded, between 6.1% and 9.1% individuals from sympatric lessonae and ridibunda populations showed introgression of an albumin allele. No gene introgression was found in allopatric lessonae populations from the Leningrad region or in ridibunda from Alma Ata and southern Bulgaria.     

Vecteurs et instrumentation,pour l’imagerie peroperatoire (V2iP)

ObjectiveThe meaning of this work was to develop a new medical imaging technique aimed to assist the surgical act during the resection of cancerous tumors.MethodThis technique is based on both the specificity of anti-tumor monoclonal antibodies or anti-neovessels peptides and the sensitivity of fluorescent detection. The objective was to develop and offer to surgeons the most effective vector-fluorophore-detection probe association in order to help them to significantly improve the patient's recovery. The development of a fluorescent detection probe fulfils two requirements: avoiding the injection of radioactive molecules which calls for difficult protection procedures and offering such detection to abdominal surgery, for which the background noise caused by the use of radioisotopes makes this technique hardly efficient. The experimental part of the project had the aim of comparing, within animals, the sensitivity and specificity of these techniques. Preclinical study has also been realized for fluorescent markers. Such studies had to show the benefits of the optical method compared to the radioisotopic method for oncology surgeons.ResultsAn industrial prototype of the probe has been developed and tested on animals after injection of the tumor specific molecule conjugated to a fluorescent dye developed within the frame of the project. The digestive tumors could perfectly be visualised.ConclusionThis surgical imaging technique should have a major impact on the practices of oncology surgeons and should lead to less complementary therapies and therefore more comfort for the patients.     

Synthesis,Protonation Behavior,Conformational Analysis,and Regioselective Enzymatic Acylation of the Novel Diamino Analogue of (E)-5-(2-Bromovinyl)-2′-deoxyuridine (BVDU)

Abstract

(E)-3′,5′-Diamino-5-(2-bromovinyl)-2′,3′,5′-trideoxyuridine (5), the diamino analogue of BVDU (1), was synthesized from BVDU. The protonation behavior of 5 has been studied by means of pH-metric measurements and NMR spectroscopy. This study allows the determination of the basicity constants and the stepwise protonation sites. Thus, the main species at physiological pH is the monoprotonated form. The conformational analysis of this nucleoside analogue was also carried out through ¹H NMR spectroscopy. In addition, a convenient synthesis of N-3′ and N-5′ acylated derivatives was developed by regioselective enzymatic acylation. Thus, Candida antarctica lipase B (CAL-B) selectively acylated the 5′-amino group, thus furnishing nucleosides 8. On the other hand, immobilized Pseudomonas cepacia lipase (PSL-C) exhibited the opposite selectivity, conferring acylation at the 3′-amino group, thus affording derivatives 9.     

An Alternative Synthesis of (2R,6R)-(–)-2,6,10-Trimethylundecyl Bromide,the Key Intermediate in the Synthesis of Natural α-Tocopherol

Crystalline aromatic l-amino acid decarboxylase from Micrococcus percitreus is inactive in the absence of pyridoxal phosphate (PLP). The inactive form of the enzyme shows absorption at 340 nm and contains one mol of PLP per mol of enzyme. Binding of PLP to the inactive form is accompanied by a pronounced increase in absorbance at 415 nm. The amount of PLP that binds to this holoenzyme is 2 mol per mol of enzyme. The inactive half-resolved form, i. e. semiapoenzyme, is obtained again by dialysis of the holoenzyme against phosphate buffer. When the semiapoenzyme is dialyzed against phosphate buffer containing 3,4-dihydroxyphenyl-l-alanine, it loses the absorption at 340 nm with the loss of PLP. This apoenzyme regains the activity and absorption at 340 nm and 415 nm on association with PLP.     

5′-O-Aliphatic and amino acid ester prodrugs of (−)-β-d-(2R,4R)-dioxolane-thymine (DOT): Synthesis,anti-HIV activity,cytotoxicity and stability studies

A series of (?)-β-d-(2R,4R)-dioxolane-thymine-5′-O-aliphatic acid esters as well as amino acid esters were synthesized as prodrugs of (?)-β-d-(2R,4R)-dioxolane-thymine (DOT). The compounds were evaluated for anti-HIV activity against HIV-1_LAI in human peripheral blood mononuclear (PBM) cells as well as for their cytotoxicity in PBM, CEM and Vero cells. Improved anti-HIV potency in vitro was observed for the compound 2–4 (5′-O-aliphatic acid esters) without increase in cytotoxicity in comparison to the parent drug. Chemical and enzymatic hydrolysis of the prodrugs was also studied, in which the prodrugs exhibited good chemical stability with the half-lives from 3 h to 54 h at pH 2.0 and 7.4 phosphate buffer. However, the prodrugs were relatively labile to porcine esterase with the half-lives from 12.3 to 48.0 min.     

Theoretical studies on all-metal binuclear sandwich-like complexes M2(η4-E4)2 (M=Al, Ga, In; E=Sb, Bi)

A series of all-metal binuclear sandwich-like complexes with the formula M(2)(η(4)-E(4))(2) (M=Al, Ga, In; E=Sb, Bi) was studied by density functional theory (DFT). The most stable conformer for each of the M(2)(η(4)-E(4))(2) species is the staggered one with D (4d) symmetry. The centred metal-metal bond in each M(2)(η(4)-E(4))(2) species is a covalent single bond, with the main contributors to these covalent bonds being the a(1) and e orbitals. For all these species, the interactions between the centred metal atoms and the all-metal ligands are covalent; η(4)-Sb (4) (2-) has a stronger ability to stabilize metal-metal bonds than η(4)-Bi (4) (2-). Nucleus-independent chemical shifts (NICS) values and molecular orbital (MO) analysis reveal that the all-metal η(4)-Sb (4) (2-) and η(4)-Bi (4) (2-) ligands in M(2)(η(4)-E(4))(2) possess conflicting aromaticity (σ antiaromaticity and π aromaticity), which differs from the all-metal multiple aromatic unit Al (4) (2-). In addition, all of these M(2)(η(4)-E(4))(2) species are stable according to the dissociation energies of M(2)(η(4)-E(4))(2)?→?2 M(η(4)-E(4)) and M(2)(η(4)-E(4))(2)?→?2 M?+?2E(4), and these stable species can be synthesized by two-step substitution reactions: CpZnZnCp?+?2E (4) (2-) →?[E(4)ZnZnE(4)](2-)?+?2Cp(-) and [E(4)ZnZnE(4)](2-)?+?2 M (2) (+) →?E(4)MME(4)?+?2Zn(+).     

Absolute configuration of 2′(R)-acetylmontrifoline and 2′(R)-montrifoline,furoquinolines from the fruits of Teclea nobilis

A phytochemical study on the alkaloids from Teclea nobilis yielded five furoquinolines, including the new acetylmontrifoline. The structures were elucidated from extensive 2D-NMR and MS experiments. The absolute configuration of the chiral center of montrifoline and of acetylmontrifoline was established as R by analysing the Mosher's derivatives and chemical modifications, respectively. All the five furoquinolines showed weak in vitro antiplasmodial activity against Plasmodium falciparum, montrifoline being moderately active (56 μg/ml) and not cytotoxic.     

Stereoselective Synthesis of (2R, 3S)-2-Benzyl-2-hydroxy-3- (3,4-methylenedioxybenzyl)-γ-butyrolactone from L-(+)-Arabinose

As a model experiment for the stereoselective synthesis of optically active cis-α,β-dibenzyl-α-hydroxy-γ-butyrolactone, (2R, 3S)-2-benzyl-2-hydroxy-3-(3,4-methylenedioxybenzyl)-γ-butyrolactone (3) was stereoselectively synthesized from L-(+)-arabinose.     

维生素E的功能、吸收与代谢(2)

在VE转运过程中,α-生育酚结合蛋白(α-TBP)对α-生育酚的特异性转运有重要作用。从肝细胞质中分离到2种不同作用的TBP:一种是30×103TBP,只存在肝细胞中,其功能是选择性地将α-生育酚混入刚形成的低密度脂蛋白(VLDL);另一种是15×103TBP,分布在所有的主要组织中,其功能可能是与α-生育酚在细胞间的分布有关。在α-生育酚进入组织器官的过程中,SR-BI(scav-enger receptor class B type I)对α-生育酚从膜蛋白到特定组织的转运具有重要的作用。敲除SR-BI基因大鼠的睾丸、卵巢、肺部和大脑的α-生育酚的浓度显著下降,而细胞膜的α…