Synthesis of N-(alkoxycarbonyl or alkoxycarbonyl-methyl-alkoxyphosphonyl)-α-amino-O,O-diphenyl phosphonates and their bioactivities

With phosphoric formic acid (PFA) and its analog,phosphonoacetic acid (PAA),as the lead compounds,α-amino phosphonates were introduced into PFA and PAA.The derivatives oi N-( alkoxycarbonyl-aikoxyphosphonyl)-α-arnino phosphonates (Ⅰ) and N-(alkoxycarbonyl-methyt-alkoxyphosphonyl)-α-amino phosphonates (Ⅱ) with the N-terminal of amino phosphonates bonding to phosphorus atom of PFA and PAA were synthesized via the reaction of the corresponding phosphonyl chloride with a-amino phosphonates in the presence of a base.The 31P NMK spectra of Ⅰ and Ⅱwere determined.It is found that the coupling constants 3Jpp with R3 being alkyl group were lower than those with R3 being (substituted) phenyl,and this result was discussed.The preliminary bioassay showed that some of the compounds Ⅰ and Ⅱhave better activities against tobacco mosaic virus (TMV).The inhibitory was higher than that of DHT (2,4-dioxyhexahydro-1,3,5-triazine).In addition,some of the compounds showed the activity against cancer cells.     

SYNTHESIS OF POLY（3,4-AZOPYRIDYLENE） AND OXYGEN-BINDING AFFINITY OF ITS COMPLEX WITH COBALTPORPHYRIN

Synthesis and characteristics of poly(3,4-azopyridylene) (PAP), conductivity and oxygen-binding affinity of its complex with meso-α,α,α,α-tetrakis(o-pivalamidophenyl) porphyrinatocobalt(Ⅱ) (CoP) were studied. PAP was prepared by oxidative polymerization of 3,4-diaminopyridine (DAP) in DMF solution using CuCl/pyridine as the catalyst. IR and NMR results showed that the peak of amido group in DAP was converted to the azo group in PAP and a π conjugated polymer was synthesized. The average molecular weight of PAP was determined to be 5.0 × 103. The PAP-CoP complex was prepared by complexing the pyridyl group of PAP with the fifth coordination site of CoP in DMF solution. In comparison with the CoP complex with a non-π conjugated polymer, the PAP-CoP complex shows good electroconductivity of 5.8 × 10-6 Scm-1. The PAP-CoP complex displays a reversible change in the UV-Visible absorption spectrum from the deoxy form to the oxy or oxygen-binding one with an isosbestic point, in response to the partial oxygen pressure of the atmosphere. The oxygen-response behavior was monitored at the absorbance ascribed to the oxy form at 548 nm to give the oxygen-binding affinity.The oxygen-binding equilibrium curves of PAP-CoP complex obey a Langmuir isotherm. DMF has great effects on the oxygen-binding properties of the PAP-CoP complex. The oxygen-binding affinity of PAP-CoP complex in the solid state is higher than that in DMF solution. With decreasing temperature, the oxygen-binding affinity of the PAP-CoP complex increases.     

Synthesis of Chiral 2,5—Bis（oxazolinyl） thiophenes and Their Application as Chiral Shift Reagents for 1,1′—Bi—2—naphthol

A series of C2-symmetrical chiral 2,5-bis (4′-alkyloxazolin-2-yl) thiophenes (thiobox) have been synthesized from thiophene-2,5-dicarboxylic acid by sequential amidation with a chiral ethanolamine,conversion of hydroxyl to chloro group, and base-promoted oxazoline ring formation.As demonstrated by (-)-2,5-bis[4′-(S)-isopropyloxazolin-2′-yl] thiophene,these thiobox systems exhibited remarkable chirality recognition of 1,1′-bi-2-naphthol giving rise to pronounced shifts in the ^1H NMR signals of the latter axial chiral compound at the positions of C-3,C-4,C-5,and C-8.     

Synthesis,Crystal Structure and Fluorescence Property of N-n-butyl-4-[di(bromoethyl)]amino-1,8-naphthalimide

The halogen as a kind of alkylating reagent is used to introduce new group to realize the fluorescence sensors efficient of metal ion detection. The substituent at C-4 position was double bromine, which defined that the halogen as an alkylating reagent should be further researched and detected for Hg2+. Therefore, the N-n-butyl-4-[di(bromoethyl)]amino-1,8-naphthalimide has been synthesized to detect some metal ions. The title compound has been prepared via substitute reaction and was characterized by IR, 1H NMR, 13 C NMR, and MS. It crystallizes in triclinic, space group P1 with a = 9.0071(18), b = 9.804(2), c = 13.073(3) ?, α = 73.17(3), β = 71.73(3), γ = 62.95(3)o, Z = 2, V = 961.5(3) ?3, Dc = 1.666 g/cm3, F(000) = 484, μ(Mo Kα) = 4.232 mm-1, R = 0.0429 and w R = 0.1004. The presence of intermolecular hydrogen bonds as well as π-π stacking interaction led to the stability of the compound. The fluorescence intensity was obviously lower than that of other ions when Hg2+ was added with the concentration of 1 × 10~(-5) mol·L~(-1).     

α-氨基酸与氯化铷在水溶液中焓相互作用参数

The mixing enthalpies of aqueous heavy rare alkali metal chloride RbC1 solutions with aqueous α-amino acid (Loglycine, L-alanine and α-aminobutyric acid) solutions, as well as the dilution enthalpies of RbC1 and α-amino acid solutions in pure water had been measured at 298.15K. The transfer enthalpies of RbCI from pure water to aqueous α-amino acid solutions could be obtained from these data. The enthalpic pair interaction parameters of RbC1 with α-amino acid in water have been evaluated according to the McMillan-Mayer theory and discussed in terms of the electrostatic interaction, structure interaction and Savage-wood group additivity mode.     

CRYSTAL STRUCTURE DETERMINATION OF DESHEPTAPEPTIDE (B24—B30)-INSULIN

Desheptapeptide (B24—B30)-insulin (DHPI), an essentially inactive insulin analog, is crystallized in space group P2_12_12_1 with two molecules in an asymmetric unit. The orientations of the molecules in the crystal cell have been determined by using Patterson search method at 6 resolution and the positions of the molecules are deduced from translation function calculation and R search at 3. resolution. After using the rigid body refinement (CORELS) further to refine the orientational and positional parameters as well as the initial energy restrained refinement (EREF) for the model, the crystallographic R valueis reduced to 0.384 at 3 resolution. The initial Fourier map shows that the B-chain N-terminal (B1—B8) and C-terminal (B20—B22)segments, compared with the native 2 zinc insulin, exhibit drastic conformational changes, but the three helices of B- and A-chains and their relative arrangement are essentially kept in DHPI.     

手性铜(Ⅱ)-席夫碱配合物催化苯乙烯不对称环丙烷化反应

Twelve chiral copper(Ⅱ) Schiff base complexes, derived from (R) (+) 2 amino 1,1 diaryl 1 propanol with substituted salicylaldehydes, were examined as a catalyst for asymmetric cyclopropanation of styrene with ethyl diazoacetate. It was found that the substituents at 3 and 5 positions of salicylaldehyde in the ligands had great effects on catalytic activity and enantioselectivity of the catalyst. The complex with strong electron withdrawing group (NO 2) at 5 position and the smallest stereo hinder (H) at 3 position of salicylaldehyde showed highly catalytic activity and enantioselectivity, up to ee =87 4% for trans and ee =82 8% for cis isomers respectively, and the ratio 39/61 of cis to trans isomers was obtained at 40 ℃ with 1,2 dichloroethane as solvent.     

Structure effect of nucleotides in terbium(Ⅲ)-nucleotide fluorescent reaction—-New evidence for the binding sites of terbium(Ⅲ) on nucleotides

Upon addition of Tb~(3+) to 16 nucleotides and homopolynucleotides, all of them showeda characteristic green emission from Tb~(3+), but with much different intensity, upon excitation inthe aromatic region of bases. The result suggested that nucleotides with at least one carbonylgroup in nucleotide bases are better enhancers to the fluorescence of Tb3+. The complexes of ATP,GDP and GTP with T5~(3+) are synthesized as two types of models. Guanine tpye nucleotides withone carbonyl group in the bases are the best enhancers, while adenine type nucleotides with nocarbonyl group in the bases are poorest enhancers to the fluorescence of Tb~(3+). Comparing theIR spectra of ATP, GTP, GDP and their Tb~(3+) complexes suggested that C-6 carbonyl group inGTP and GDP may be involved in complex formation, which may be responsible for the effectiveenergy transfer. This is further supported by comparing the UV spectra of ATP, Poly(A), GTP,and Poly(G) with their Tb~(3+) complexes in water solution.     

Synthesis of Well-defined Poly(tetrahydrofuran)-b-Poly(α-amino acid)s via Cationic Ring-opening Polymerization(ROP) of Tetrahydrofuran and Nucleophilic ROP of N-thiocarboxyanhydrides

The synthesis of block copolymers of poly(tetrahydrofuran)-b-poly(α-amino acid)(PTHF-b-PAA) is challenging since it is difficult to combine the two blocks produced via different/conflicting ring-opening polymerization(ROP) mechanisms. In this contribution, the cationic ROP of THF is catalyzed by rare-earth triflate [RE(OTf)_3] and terminated by 2-(t-butyloxycarbonyl-amino) ethanol(BAE). After the deprotection of tbutyloxycarbonyl(Boc) group, the chain end of PTHF is quantitatively changed to amino group which thereafter initiates the nucleophilic ROP ofα-amino acid N-thiocarboxyanhydrides(NTAs). Both polymerizations are well controlled, generating PTHF and PAA segments with designable molecular weights(MWs). PTHF-b-polylysine(PTHF-b-PLys) and PTHF-b-polysarcosine(PTHF-b-PSar) are obtained with MWs between 8.6 and28.7 kg/mol. The above amphiphilic diblock copolymers form micelles in water. PTHF_(40)-b-PSar_(32) acts as a surfactant to stabilize oil-in-water emulsions. Both segments of PTHF-b-PAA are biocompatible and promising in the biomedical application.     

Mono-Allylation of Gem-Diacetates with Allylsamarium Bromide

Our group have explored the reaction of allylsamarium bromide with a variety of substrates, such as N-(2-aminoalkyl)benzotriazoles1, imines2, nitriles3, diorgano diselenides4, disulfides5, isocyanates6 and nitroalkenes7. Here we wish to report the monoallylation of gem-diacetates with allylsamarium bromide. Gem-diacetates are stable in neutral and basic media, thus they are frequently used to protect aldehydes8. However, the presence of two leaving groups at the same carbon may make carbon …     

Synthesis and Complexation Properties of Novel Chiral Calix[4]-1,3-aza-crown and Calix[4]arene Hydrazone Derivative

<正>Refluxing calix[4]-1,3-substituted benzaldehyde derivative(4) with glycine hydrazide derivative,we obtained a novel calix[4]arene hydrazone derivative(5) via"1+2"condensation in a yield of 78%.In the reaction of compound 4 with L-leucine hydrazide derivative at room temperature,lariat calix[4]-1,3-aza-crown(6) with chiral amino acid group as branched chain was synthesized via"1+1"addition in a yield of 70%.The preliminary extraction experiments suggested that hosting compounds 5 and 6 possessed good complexation abilities forα-amino acids.     

Synthesis of N-(methoxycarbonyl or isopropylcarbamoyl- methoxyphosphonyl)-α-amino acid ester and their stereomers

N-(methoxycarbonyl-methoxyphosphonyl)-α-amino add esters (I) were synthesized via the reaction of the corresponding phosphonyl chloride with amino acid ester hydrochlorides in the presence of a base. Compound I was aminated to yield N-(isopropylcarbainoyl-methoxyphosphonyl)-α-amino acid esters (II). With l-amino acids as starting materials, the isomers of products I and II were separated and their configurations were confirmed by the single crystal X-ray diffraction of II.     

SYNTHESIS OF THE 3'-HALF MOLECULE OF YEAST ALANINE tRNA

This paper deals with the synthesis of the 3'-half molecule of yeast alanine transfer RNA (tRNA_y~(Ala)) by ligation with T_4 RNA ligase of three component oligonucleotide fragments corresponding to nucleotides 36-45(Ⅰ), 46-57(Ⅱ) and 58-76(Ⅲ) in succession extending from the 3'-end to the 5'-end. First, in a ratio of acceptor to donor at 1.5 to 1, we adopted a method of three successive reactions, namely, the 5'-phosphorylation of the nonadecamer (Ⅲ), ligation with the dodecamer(Ⅱ) and the 5'-phosphorylation of the ligation product formed; with one isolation step and obtained the 5'-phosphorylated 31mer(46-76) (Ⅳ) in an overall yield of 70%. Then the 31met(Ⅵ) as a donor was ligated with 3 times of decamer(Ⅰ) to form the 41met(36-76) (Ⅴ), the 3'-half molecule of tRNA_y~(Ala)). The yield was 67%. After 5'-phosphorylation, (Ⅴ) was ligated with the natural 5'-half molecule to form the semi-synthetic tRNA_y~(Ala)), which was biologically active, i. e. accepting and transferring (~3H)-alanine into p     

Synthesis of novel fullerene α-amino acid conjugates

Aspartic acid and glutamic acid with protectedα-amino andα-carboxyl groups had been used to react with the activated hydroxyl group of N-substituted 3,4-fullero pyrrolidine.The products were deprotected,affording two monofullereneα-amino acids,monofullerene aspartic acid(mFas)and monofullerene glutamic acid(mFgu).Then a bifullerene glutamic acid conjugate (bFguC)was synthesized by reaction of mFgu containing protected amino group with N-substituted 3,4-fullero pyrrolidine.     

A novel and versatile method for the enantioselective syntheses of tropane alkaloids

A full account of the novel and flexible approach to hydroxylated 8-azabicyclo[3,2,1]octan-3-ones and 9-azabicyclo[3,3,1]nonan-3-ones is presented.Using keto-lactams as the starting materials,this two-step method consists of silyl enol ether formation with TBDMSOTf,lactam activation with Tf2O/DTBMP,and halide-promoted cyclization.Radical dechlorination of the resulting 1-halotropan-3-ones led to the corresponding hydroxylated tropan-3-ones,which can be hydrogenated to yield3,6-dihydroxytropanes.Starting from optically active keto-lactams,the method has been applied to the enantioselective syntheses of(+)-(1S,3S,5R,6S)-pervilleine C(6),(+)-(1S,3R,5S,6R)-valeroidine(3),(+)-(1S,3S,5R,6S)-dibenzoyloxytropane(8),and(+)-(1S,3S,5R,6S)-merredissine(9).     

SELECTIVE REDUCTION OF 3,17—DIOXO—STEROIDS TO 17β-HYDROXY-3-OXO-STEROIDS

11β-Hydroxy-androst-4-en-3,17-dione(1a),androst-4,9(11)-dien-3,17-dione-(2a),androst-4-en-3,11,17-trione(3a),11α-methoxy-androst-4-en-3,17-dione(4a)and 11β-metboxy-androst-4-en-3,17-dione(Sa)were selectively reduced tothe corresponding 17β-OH derivatives in one step without the protection of 3-oxo(and 11-oxo,in the case of 3a)group with the yields ranging from 65% to79%.In these reactions,the ditute NaBH_4(or KBH_4)solution in methanol wasadded dropwise to the 3,17-dioxo-steroids solution in methanol-benzene-pyridine,while the reaction mixtures were well stirred at -5～5℃.Acid(such as gtacialacetic acid)was added to quench the reactions.The resulted testosteronederivatives(1b～5b)were purified by flash chromatography.This method appties to the reduction of other 3,17-dioxo-steroids such as△~1-3-one,△~(1.4)-3-one,△~(4.6)-3-one,△~(1.4.6)-3-one containing compounds.     

Stereoselectivities in α- and β-Amino Acids Catalyzed Mannich Reactions Involving Cyclohexanone

The effects of two different amino acid catalysts on the stereoselectivities in the direct Mannich reactions of cyclohexanone,p-anisidine and p-nitrobenzaldehyde were studied with the aid of density functional theory.Transition states of the stereo-determining C C bond-forming step with the addition of enamine intermediate to the imine for the L-proline(·-amino acid) and (R)-3-pyrrolidinecarboxylic acid(·-amino acid)-catalyzed processes were reported.B3LYP/6-31G calculations provide a good explanation for t...     

Crystal Structure of 5—（l—Menthyloxy）—3—chloro—4— Pyrrolidinyl—2（5H0—f

The molecular structure of the title compound 5-(l-menthyloxy)-3-chloro-4-pyrrolidinyl-2(5H)-furanone, C18H28ClNO3(Ⅰ), has been determined by X-ray diffraction at 296(1)K. The crystal is monoclinic with space group P21, a=9.457(3), b=10.413(3), c=9.525(2), β=95.19(2)°, V=934(1) 3, Z=2, Mr=341.88, Dx=1.22 g/cm3, μ=2.15 cm-1, F(000)=368. The final R factor is 0.059, and Rw is 0.065 for 1020 observed reflections with I≥3σ(I). The absolute configuration at C(14) of the acetal carbon was proved to be S, taking into account the known configuration of 1R, 2S, 5R-menthyl moiety. There are three rings in the molecule of this compound: the furanone ring, the pyrrolidine ring and the mentholoxy group ring. The franone ring is connected with the pyrrolidine ring and the mentholoxy ring by N atom and μ2-O bridge atom respectively.     

SYNTHESIS AND CRYSTAL STRUCTURE OF {C(η~5-C_5H_5)_4Nd_4(μ_4-O) (μ_2-Cl)_8)]·[Li(dme)_2THF]_2

<正> The reaction of (η5-C5H5)3Nd·THF and NdCl3·2LiCl·nTHF in solution at room temperature gave rise to[(η5-C5H5)4Nd4(μ4-O)(μ2-Cl)8][Li(dme)2THF]2 (Mr = 1654.44). Crystals of the compound were obtained at about - 10℃. The intensity data were collected under nitrogen atmosphere at-60℃. The crystal belongs to the rhombic system with space group Pna21 and the unit cell parameters : a=19. 010(7),b = 23. 231(6) ,c= 14. 180(4) A ;V = 6261. 91 (A3) , DC= 1. 67 (g/cm3), λ(MoKa) = 0. 71069A,F(000) = 3240,μ(mm-1) = 3. 660;Z = 4. Least-squares refinement with anisotropic temperature factors for all non-hydrogen atoms led to the final R=0. 054, Rw = 0. 056. The molecule is made up of the anion group and the cation. The oxygen atom links four Nd3+together as μ4-bridge. The eight chlorine atoms form the eight chlorine-bridge bonds among four Nd3+ions. The average bond length is : Nd-O=2. 374,Nd-Cl = 2. 811,Nd-C=2. 777,Nd(a)- Nd(b) = 3. 872A.The bond angles of Nd(a) -Nd (b)-Nd(c) fall in the range of 62~63°,th     

Stereoselective synthesis of (5R,6S)-6-acetoxy hexadecanolide——The major component of the oviposition attractant pheromone of the mosquito Culex pipens fatigans and its enantiomer from L-glutamic acid

A concise synthesis of the mosquito oviposition attractant pheromone, (-)-(5R, 6S)- and(+)-(5S 6R)-6-acetoxy hexadecanolide from L-glutamic acid is described. The key steps are theinversion of the configuration at C-4 of 7, and the formation of δ-lactone from the γ-lactonethrough ring enlargement.