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α-Hydroxyphosphonic acids and their derivates have diverse and interesting biological and biochemical properties。This article reviews the recent studies on the synthesis of optically active α-hydroxyphosphonic acids and α-hydroxyphosphonates by chiral auxiliary induced and chiral catalyst catalysed methods.
The transition metal-catalyzed cross-coupling reaction to form sp2 C—C or C-hetero atom bonds is one of the most important methods for modern organic synthesis。In comparison with Pd and Ni，copper is a cheap metal with low-toxicity。In this review the newest development of the Cu catalysts in C—N cross-coupling reactions is summarized.
Naturally occurring terpenes constitute the largest group of natural products with complicated and variable structures and a great number of important biological activities。2-Methyl-D-erythreitol 4-phosphate (MEP) pathway is a newly found and established biosynthetic route for terpenoids and all the enzymes involved in this pathway can be used as targets for the screening of new antibiotics。Progress in chemical and enzymatic preparation of the key intermediates in MEP pathway，namely 1-deoxy-D-xylulose 5-phosphate and 2-methyl-D-erythreitol 4-phosphate is reviewed with the emphasis on the synthesis of these two compounds with isotope labels.
Mesembrine，an Aizoaceae alkaloid，was isolated from the Mesembryanthemum tortuosum and characterized by Bodendorf’s group in 1957。In addition to its structural feature and interesting bioactivities has attracted much attention，mesembrine has been one of the most interesting targets in synthetic organic chemistry for the past 40 years。To date，over 40 total and formal syntheses have appeared。In this paper，31 total and formal syntheses of mesembrine are reviewed.
The copper-catalyzed Heck reaction of acrylic ester or styrene with aryl halide gave the coupling products in good to excellent yields in aqueous two-phases system in 75～85 ℃ by using L-proline as a ligand。This method provides a new simple and inexpensive access to the Heck reaction。The structures of the products were confirmed by using spectroscopic techniques such as IR，1H NMR，13C NMR and comparing their melting points with known literature.
A N3O2-donor macrocycle bearing a naphathalic sulfonic group derived from 8,11,14-triaza-5,6: 16,17-dibenzo-1,4-dioxacycloheptadecane has been synthesized，and its structure was characterized by 1H NMR，MS data and elemental analysis。The interactions of the target compound with CT (calf thymus) DNA have been investigated by the ultraviolet spectrophotometry and fluorescence spectrophotometry。The results showed that the binding model between the N3O2-donor macrocycle and CT DNA was intercalation，with the binding constants being ＝20706.9 dm3•mol－1 and ＝12416.9 dm3•mol－1。The com-bination was the enthalpy driven reaction.
To develop novel pesticide lead compounds with high activity，low toxicity and low residue，24 novel 5-(4-hydroxybenzyl)-2,4-imidazolidinedione (hydantoin) esters were synthesized with cyclization and esterification using L-tyrosine as raw material by simulating the structure of natural inhibitor against AdSS synthetase，and structurally confirmed by m.p.，IR，1H NMR and elemental analysis。X-ray diffraction analysis of 6m was studies as C18H16N2O5，Mr＝340.33，monoclinic，space group P2(1)/c，a＝0.86071(17) nm， b＝1.1167(2) nm，c＝0.93826(2) nm，β＝115.10(3)°，V＝0.8166(3) nm3，Dc＝1.384 g/cm3，Z＝2，F(000)＝356，m(Mo Kα)＝0.103 mm－1，final R＝0.0359，wR＝0.0998。The preliminary bioassay results indicated that some of these compounds had certain inhibition activities against Triticum aestivum and Arabidopsis thaliana，while some of them could promote the growth of Zea mays at the concentration of 200 μg/mL.
Two kinds of novel β-dihydroxyarylporphyrins were synthesized by direct reaction of β-nitroporphyrin with 2,3-dihydroxynaphthalene and o-dihydroxybenzene respectively，and structurally characterized by UV，1H NMR，IR，MS and elemental analysis。The reaction mechanism was discussed。The agarose gel electrophoresis results show that the novel compounds cause significant cleavage to pBR322 plasmid DNA，which have good application prospects as photosensitizers or their precursors.
A series of 3-[substituted pyridyl (or thiazolyl)methyl]-1,2,3-triazolo[4,5-d]pyrimidin-7-ones were synthesized via the tandem Aza-Wittig reaction annulation。The carbodiimides 5，obtained from the aza-Wittig reaction of iminophosphorane 4 with aromatic isocyanates，reacted with a variety of primary ali-phatic amines in the presence of a catalytic amount of EtONa to give the target compounds 7 in moderate yields。The preliminary bioassay indicated that some of the target compounds displayed good herbicidal ac-tivity against Brassica campestris L at the dosage of 100 mg/L。
Chiral auxiliary controlled asymmetric reaction is one of the main methods in asymmetric synthesis。Under the control of the various chiral Evans auxiliaries，different Grignard reagents were added asymmetrically to the substrates 1 by the way of 1,4-Michael addition reaction and a series of Michael addition products 2a～2h have been synthesized。The results showed that the steric hindrance of the chiral auxiliaries and the Grignard reagents was the main factor to influence the stereoselectivity of Micheal addition。When the chiral auxiliaries and the Grignard reagents were aryl-substituted，good yield and high stereoselectivity could be achieved up to 95% de，while the de values were lower than 70% when the substituent groups were alkyl，benzyl or alcyl.
(4R)-5,5-Dimethyl-4-benzylthiomethyl-2-oxazolidinone was synthesized from readily available amino acid L-cysteine via asymmetric reactions including the thioalcohol protection of L-cysteine，esterification，amine protection，Grignard reaction and cyclization in an overall yield of 31%。The structure was characterized by IR，1H NMR，13C NMR and MS techniques.
Seven macrocyclic diterpene compounds were isolated from Boswellia carterii Birdwood (Frankincense) and purified by silica-gel column chromatorgraphy and preparative thin-layer chromatography (TLC)。Their structures were elucidated as incensole acetate (1)，incensole (2)，incensole oxide acetate (3)，isoincensole acetate (4)，incensole oxide (5)，isoincensole oxide (6) and isoincensolol (7)。Compound 7 was a novel compound and compound 4 was isolated from this genus for the first time。Compounds 1～7 suppressing Bel-7402，Hela and SW-480 cells were investigated in vitro with cytotoxic activity.
A convenient approach for synthesis of the imidazole derivatives of helicid 4a～4h is presented via condensation of helicid，2-hydroxy-1,2-diarylethanone (2a～2d)，ammonium acetate and alkyl amine，using iodine as efficient catalyst。The structures of the target compounds 4a～4h were characterized by 1H NMR，13C NMR，IR and HRMS techniques。Their calm activities were investigated in healthy mice，and compound 4e showed favorable calm activity compared with helicid.
Pd(OAc)2 catalyzed Sonogashira cross-coupling reaction under amine-，copper-，and phosphine-free reaction conditions by ultrasound irradiation。The synthetic method was established via the aryl iodide Sonogashira reaction。The procedure has the advantages of mild conditions，short reaction time and high yields.
Menthyl bromide and neomenthyl bromide were synthesized from L-menthol via highly stereoselective bromination reactions。When a mixture of concentrated hydrobromic acid and anhydrous zinc bromide was used as the brominating agent，menthyl bromide was stereoselectively formed。Neomenthyl bromide was highly stereoselectively obtained in the circumstance of using phosphorus tribromide as a brominating agent.
A synthesis of 2-amino-3-cyano-4-aryl-7,7-dimethyl-5-oxo-4H-5,6,7,8-tetrahydrobenzo[b]- pyrans from aromatic aldehyde，malononitrile and 5,5-dimethyl-1,3-dioxocyclohexane using (2-dimethy- laminoethyl)(benzyl)dimethylammonium chloride ([PhCH2Me2N＋CH2CH2NMe2]Cl－) as catalyst (5 mol%) was described which provided several advantages such as excellent yield，short reaction time，simple ex-perimental and work-up procedure，reusability of catalyst and benignity to environment.
Five compounds were isolated from the fruits of Physalis alkekengi L。var。franchetiI (Mast.) by silica gel column，D101 macroporous column，Sephadex LH-20 column，ODS column chromatography and HPLC。On the basis of the chemical and spectral methods，the structures of the five compounds were elucidated as alkekengilin A (1)，alkekengilin B (2)，physalin D (3)，physalin P (4) and 4,7-didehydro-neophysalin B (5)。Among these compounds，1 and 2 are two new compounds，and others are known compounds。
Ten novel benzoyl ureas containing a 1,3,4-thiadiazole group were synthesized by the reaction of 2-amino-5-substituted phenyl-1,3,4-thiadiazole and 2,6-difluorobenzoyl isocyanate，and structurally con-firmed by 1H NMR，IR，ESI-MS techniques and elemental analysis。Preliminary bioassay test indicated that some compounds showed insecticidal activity。Compounds 3d (3,5-(CH3)2) and 3g (4-C4H9) exhibit good insecticidal activity against Aphis craccivora with higer than 90% mortality.
Eleven 6-(substituted)-3-(3,4,5-trimethoxyphenyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives 5a～5k were synthesized by cyclization of 4-amino-5-(3,4,5-trimethoxybenzyl)-3-mercapto-1,2,4- triazole (4) with various substituted aromatic acids through a single step reaction。IR，1H NMR，MS techniques and elemental analysis confirmed the structures of the newly synthesized compounds。Preliminary bioassays indicated that some compounds showed fungicidal activity.
Cellulose is a very valuable renewable resource。A variety of useful chemical compounds can be produced by the reactions of cellulose。The reactions of cellulose in supercritical water are reviewed。In the absence of a catalyst，the products for cellulose hydrolysis in supercritical water are glucose，fructose and oligomers。The experimental set-up，product distribution as well as mechanism of cellulose hydrolysis in supercritical water are discussed。Using a catalyst such as Ni，Pt，Ru，or KOH，the gasification reaction of cellulose in supercritical water occurred，and the main gas products produced were H2，CO2 and CH4。The hydrogen production processes from cellulose and glucose，which is the main product of cellulose hydrolysis reaction，are introduced。The prospect of cellulose reaction technology in supercritical water is discussed.
Preparation and reaction of metallacyclic compounds have attracted increasing interest in recent years, since many synthetically important transition-metal-assisted reactions proceed via metallacyclic intermediates. Compared with a large number of reports on 5-membered metallacycles, there are only a few reports on 6-membered metallacycles. Because of the potential application of 6-membered metallacycles, a review is given about the preparative methods of six-membered metallacycles developed in our group as well as in other groups.
Many non-palladium catalysts have been applied to Heck reactions. Compared with palladium complexes, some non-palladium catalysts (such as nickel, copper, cobalt complexes, and so on) show many advantages in application. Catalyst systems based on platinum, rhodium, ruthenium or iron were also applied to Heck reactions in recent years. In this paper, the progress in Heck reaction catalyzed by non-palladium catalyst is reviewed.
Thioureas can be used in various areas．Based on different starting materials, reagents, solvent and catalysts, the recent ten-year progresses in the synthetic methods of thioureas are reviewed emphatically．
The recent progress in copper-catalyzed C-N cross-coupling reactions is reviewed. According to the different compounds containing nitrogen, the nucleophiles are divied into the following five categories: amino acids, amines, amides, aromatic nitrogen heterocycles and others nitrogenous compounds. The reaction systems, in which the reaction of various types of nucleophiles were carried out, including electrophile, catalyst precusor, ligand, solvent, temperature, base and reaction time, are summarized comprehensively. Based on the ligands the above rections are described in detail. Furthermore, the studies on the mechanism of these reactions are surveyed.
The C—C cross coupling reaction catalyzed by palladium complexes represents one of the most important C—C bond formation reactions. Traditionally, organo phosphines are used as the ligands to modify the catalytic properties of palladium complexes. However, most of them are air-sensitve, Labile to be oxidized and to dissociate in solution. Therefore, excess phosphorous ligands are needed to keep the catalytic activities. N-Heterocyclic carbene (NHC) reported since 1991 has been a focus in organometallic chemistry and catalysis because of its strong electronic donor properties, versatile structures that can be readily modified, and excellent coordinative ability to metal. The Pd-NHC compound has emerged as an al-ternative of Pd-phosphine compound in the promotion of C—C bond coupling reactions. In this paper, the application of the Pd-NHC complexes derived from mono-ligated NHC, chelate NHC to Heck reaction and Suzuki reaction was summarized.
Palladium-catalyzed coupling reaction plays a important role in industry. Many disadvantages were found using phosphine ligands under traditional conditions. Development and application of phosphine-free ligands have attracted much attention. This review is focused on progress in different kind of phosphine-free ligands recently.
A number of antimicrobial natural products have been isolated from endophytic fungi with diverse structures. Progress in various studies on antimicrobial components is summarized, including the host plants of these endophytic fungi, the isolation and characterization of these compounds, and their inhibitory effects against bacteria and fungi. Besides, the chemical ecology relationships between the endophytic fungi and their host plants, as well as the value of disquisition on these metabolites are briefly discussed. We hope to develop a new antibiotic with strong activity through the study of these active substances.
The synthesis of N-(2-(1H-indol-3-yl)ethyl)-2-acetylthiazole-4-carboxamide (1), which is a new algaecide from the marine bacterium, was achieved effectively from D-alanine. Its analogues 2, 3 and 4 were firstly synthesized using the similar approach. The key step was a coupling reaction via the mixed anhydride. All structures were confirmed by 1H NMR and 13C NMR spectra. The final compounds were confirmed by 1H NMR, 13C NMR and HRMS techniques, and the results are consistent with the reported natural prod-ucts.
The chalcones 2a～2l were synthesized by aldol condensation reaction of arylaldehydes with 1-aryl-2-(1H-1,2,4-triazol-1-yl)ethanones (1a～1c), which were prepared from 2-bromo-1-arylethanones. Then the intermediates 2a～2l were reacted with 2-aminobenzenethiol to give a series of 3-(1,2,4-triazol-1-yl)- benzo[b]thiazepine derivatives 3a～3l. Compounds 3a～3l were confirmed by means of elemental analysis, IR, 1H NMR, MS techniques, and compounds 2a and 3a were analyzed by X-ray single-crystal diffraction.
An efficient catalytic oxidization using a stable and safe oxone/CaCl2/TEMPO (TEMPO＝2,2,6,6-Tetramethyl-1-piperidinyloxy) system to convert alkyl or benzyl alcohols to carbonyl compounds under room temperature is described. Primary benzyl alcohols are readily oxidized to the corresponding aldehydes in excellent yields (90%～96%). Secondary alcohols are converted to corresponding ketones in 81%～85% yields. Oxidative cyclization of 1,4-diol to γ-lactone in 94% is obtained.
A convenient and effective method was developed from the starting materials acetonitrile and aryl nitrile via three steps to synthesize 3-aryl-6-methyl-1,6-dihydro-1,2,4,5-tetrazines. On the basis of which, some 3-aryl-6-methyl-1,6-dihydro-1,2,4,5-tetrazine derivatives were synthesized and characterized by elemental analysis, 1H NMR, IR and HRMS techniques. The X-ray single crystal diffraction study of 6-methyl-3-phenyl-N-(2-tolyl)-1,6-dihydro-1,2,4,5-tetrazine-1-carboxamide (5a) indicates that 5a belongs to a monoclinic system, with a＝1.3941(6) nm, b＝0.5675(2) nm, c＝2.0614(8) nm; α＝γ＝90°, β＝102.055(6)°; V＝1.5949(11) nm3. The central tetrazine ring adopts an unsymmetrical boat structure. It could be considered that the molecule had a homoaromaticity.
The FeCl3-mediated reaction of alkynols with iodine resulted in intramolecular addition of hydroxyl to alkyne to produce a wide range of iodocycloenol ethers in good to excellent yields (63%～90%) under mild reaction conditions. On the other hand, 1,2-diiodides were obtained generally in good yields (15%～88%) when propargyl alcohols were reacted with iodine in the same condition. The advantages of our procedure include a decreased amount of iodine (0.5 equiv.) as well as short reaction time (3 h). The broad scope, mild reaction conditions, and experimental ease of this transformation have made it a valuable alternative to current available methods for the preparation of iodocycloenol ethers or 2,3-diiodoalkenols.
A new bromination of methylarenes was developed through boron tribromide under the mild conditions, which is different from traditional free-radical process. The advantage of this method is the good yield and high selectivity. During investigation of electron and steric effect, it was found that substrates with various substitutional groups could give expected products in moderate to good yields. Both steric hindrance and electron effect would affect the reaction. Electron-donating substitute was favorable to bromination, while electron-withdrawing group decreased the yield. At the same time, the influence of solvent, temperature, mass of boron tribromide and reaction time on the bromination was also investigated.
3,9-Diazahexacyclo[6.4.0.02,7.04,11.05,10]dodecanes were synthesized by a head-to-tail [2＋2] photocycloaddition of 1,4-dihydropyridines. Various factors such as solvents, the concentrations of 1,4-dihydropyridine, wavelength of UV and reaction time, were studied in details. An efficient method of synthesizing 3,9-diazatetraasteranes was found, and 12 compounds were ob-tained and characterized by IR, 1H NMR, 13C NMR, MS and HRMS tech-niques.
Methoxamine hydrochloride was synthesized from p-dihydroxybenzene by O-methylation, Friedel-Crafts acylation, oximation reaction, oxime reduction and keto-amine hydrogenation reactions. All intermediates and products were characterized by IR, 1H NMR spectra and elemental analysis. The total yield was 37.6%. Compared to the traditional synthetic procedures of methoxamine hydrochloride, the procedures were temperate, convenient, economical, high-yielding and environment-friendly.
