Synthesis,Crystal Structure and Biological Activities of N-(4-Cyanopyrazole-3-yl)-α-(3,5-difluorophenyl)-O,O-diisopropyl-α-aminophosphonate

The title compound has been synthesized by the addition reaction of N-（4-cyanopyrazole-3-yl）-3,5-difluorophenyl-imine and diisopropyl phosphate. Its structure was confirmed by means of IR, ^1H NMR and elemental analysis. The single-crystal structure of the title compound was determined by X-ray crystallography. The compound crystallizes in monoclinic, space group C2/c with a = 18.9959（14）, b = 9.2212（7）, c = 22.1108（16）A^°, β= 90.1540（10）°, V = 3873.0（5） A^°^3, Dc = 1.366 g/cm^3, Z = 8, μ = 0.185, F（000） = 1664, and the final R = 0.0503 and wR = 0.1539 for 2996 observed reflections （I 〉 2σ（I））. The results demonstrate that the dihedral angle between the pyrazole and benzene rings is 105.5°, and there is a full delocalized pyrazole system with sp^2 hydridization of N（3）. The crystal structure is stabilized by two intermolecular hydrogen bonds of N（1）-H（1）…O（3） and N（3）-H（3A）…N（4）. The preliminary biological test shows that the title compound has a moderate antifungal activity.

An efficient and green preparation of 5-aminophosphonate substituted pyrimidine nucleosides under solvent-free conditions

An environmentally benign and highly efficient one-pot preparation of α-aminophosphonates under solvent-free conditions was developed. By employing this method, 5-aminophosphonate substituted pyrimidine nucleosides were synthesized in good to excellent yields starting from 5-forrnyl-2＇-deoxyuridine, aniline and dimethylphosphite.

Synthesis, X-ray Crystallographic Analysis and Bioactivities of α-Aminophosphonates Featuring Pyrazole and Fluorine Moieties

A series of novel -aminophosphonates containing pyrazole and fluorine moieties was designed and synthesized through ultrasonic-assisted condensation and solvent-free addition reactions. Their structures were verified by IR, ^1H NMR, ^13C NMR and elemental analysis. The crystal structure of diethyl[（4-cyano-1H-pyrazol-3-ylamino）（3,5-difluorophenyl）methyl]phosphonate（4a, C15H17F2N4O3P） was determined by single-crystal X-ray diffraction. Compound 4a crystallizes in the triclinic system, space group P1 with a = 8.381（3）, b = 10.103（5）, c = 11.268（3） A, α= 83.772（19）, β= 74.726（19）, γ= 70.964（18）, V = 869.9（6） 3, Mr = 370.30, Dc = 1.414 g/cm^3, Z = 2, F（000） = 384, = 0.200 mm^-1, MoKa radiation（ = 0.71073 ）, the final R = 0.0487 and w R = 0.0823 for 1582 observed reflections with I 〉 2（I）. X-ray diffraction analysis reveals that there are two planes in 4a, and the dihedral angle is 71.51°. Two intermolecular hydrogen bonds and a face-to-face … stacking interaction are observed in the crystal structure. The compounds were evaluated for their antifungal, antiviral and antitumor activities, respectively. Among them, 4b, 4c, 4g and 4h exhibit good activities on Sclerotium rolfsii Sacc at 200 μg/m L, while 4b, 4c, 4f and 4g possess good anti-TMV activities at 500 μg/m L. Unfortunately, all of the compounds showed weak antitumor activities.

Microwave-assisted Syntheses,Structures and Bioactivities of α-Aminophosphonates Containing Pyrazole and 2-Hydroxybenzyl Units

Using 3-amino-4-cyanopyrazole, salicylaldehyde and dialkylphosphite as materials, a series of a-aminophosphonates containing pyrazole and 2-hydroxybenzyl units were synthesized under microwave irradiation without solvents and catalysts. The structures of the compounds were verified by IR, 1H NMR, J3C NMR and elemental analysis. The crystal structure of diisobutyl {a-[3- （4-cyano-lH-pyrazol）amino）]-N-（2-hydroxylbenzyl）}phosphonate （4d, C19H27N404P） was deter- mined by single-crystal X-ray diffraction. Compound 4d crystallizes in the orthorhombic system, space group Pbcn with a = 17.329（4）, b = 20.091（5）, c = 12.433（3）/k, V = 4328.7（17） A3, M,. = 406.42, Dc = 1.247 g/cm3, Z = 8, F（000） = 1728,μ = 0.158 mm-1, MoKa radiation （2 = 0.71073 A）, the final R = 0.064 and wR = 0.0169 for observed reflections with I 〉 2σ（I）. X-ray diffraction analysis reveals that two planes lie in 4d, and the dihedral angle is 85.76°. Intermolecular O（1）-H（1B）-O（2）, N（1）-H（1）-N（4）, N（3）-H（3）.-.N（2） and N（3）-H（3）...O（1） hydrogen bonds are found in the structure. All the compounds were evaluated for their antiviral and antitumor activities respectively. Among them, 4d and 4e showed moderate anti-TMV activities at 500 gg/mL, and 4e possessed excellent antitumor activity against PC3 cells at 10 gmol/L.

Solvent-and Catalyst-free Synthesis and Antifungal Activities of α-Aminophosphonate Containing Cyclopropane Moiety

Nine new a-aminophosphonate derivatives containing cyclopropane moiety have been synthesized via conventional and microwave irradiation methods under solvent- and catalyst-free condition. The structures of the title compounds have been confirmed by ^1H NMR, ^31p NMR FTIR, EI-MS and FTICR-MS. Their antifungal activities were evaluated in vivo and some of the compounds were found to exhibit excellent antifungal activities against Corynespora cassiicola, Pseudomonas syringae pv. Lachrymans, Pseudoperonospora cubensis and Sclerotinia sclerotiorum.

Enantioselective synthesis of quaternary α-aminophosphonates by organocatalytic Friedel–Crafts reactions of indoles with cyclicα-ketiminophosphonates

An efficient asymmetric Friedel-Crafts reaction has been developed for the synthesis of optically active quaternaryα‐aminophosphonates with up to98%ee.The synthesis involves the reaction of cyclicα‐ketiminophosphonates with indoles using an H8‐BINOL‐derived chiral phosphoric acid(CPA)catalyst that bears electron‐withdrawing3,5‐ditrifluoromethylphenyl substituents on its3‐and3′‐positions.This Friedel-Crafts reaction of cyclicα‐ketiminophosphonates was also successful with pyrrole.

Syntheses and Crystal Structures of Two New α-Aminophosphonate Derivatives Containing Thieno[2,3-d]pyrimidine

Two new a-aminophosphonate derivatives containing thieno[2,3-d]pyrimidine, diethyl（（（6-ethyl-2-methyl-4-oxothieno[2,3-d]pyrimidin-3 （4H）-yl）amino）（4-methoxyphenyl）methyl） phosphonate （1） and diethyl（（4-bromophenyl）（（6-ethyl-2-methyl-4-oxothieno[2,3-d]pyrimidin-3 （4//）-yl）amino）methyl）phosphonate （2）, have been synthesized by a facial phosphorylated reaction, and their structures were characterized by NMR, IR, HRMS and X-ray single-crystal diffraction. Compound 1 （C21H28N3O5PS, Mr = 465.49） belongs to the orthorhombic system, space group P212121, with a = 10.83653（16）, b = 12.04906（19）, c = 18.0061（3） A, V= 2351.06（6） A3, Z= 4, Dc= 1.315 g/cm3, p = 2.177 mm-1, F（000） = 984.0, the final R = 0.0389 and wR = 0.0985 for all data. Compound 2 （C20H25BrN304PS, Mr = 514.37） belongs to the orthorhombic system, space group P212121, with a = 10.9187（5）, b = 11.9522（4）, c = 17.7667（7） A, V= 2318.60（16） A3, Z = 4, Dc= 1.474 g/cm3,μ = 4.175 mm^-1, F（000） = 1056.0, the final R = 0.0367 and wR = 0.0946 for all data.

Alum:An efficient catalyst for one-pot synthesis of α-aminophosphonates

Alum （KAl（SOa）E.12H2O） is an inexpensive, efficient, non-toxic and mild catalyst for the one-pot synthesis of α-aminopho- sphonates. A three component reaction of an aldehyde/ketone, an amine and triethyl phosphite was carried out under solvent-free conditions to afford the corresponding α-aminophosphonates in short reaction times and high yields with the green aspects by avoiding toxic catalysts and solvents. 2009 Murlidhar S. Shingare. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

The design and synthesis of a novel organophosphorus compound containing the structure of both β-amino acid and β-aminophosphonate

A novel organophosphorus compound containing the structure of bothβ-amino acid andβ-aminophosphonate is designed and synthesized.Arbuzov reaction with P（OEt）_3,the N-Boc protected iodide 3 cannot provide the desired product but 2-oxazolidinone 4 because of the neighboring-group participation of the Boc moiety.To avoid the intramolecular participation of the carbamates,the Ts protecting group is employed and the Ts-protected iodide 5 affords the target product successfully.

Direct Synthesis of α-Aminophosphonates from Amines,Alcohols,and White Phosphorus

Developing practical strategies for the synthesis of organophosphorus compounds(OPCs)from white phosphorus(P_(4))without the use of Cl_(2) and PCl_(3) remains a significant challenge.The first multicomponent oxidative α-phosphonylation of amines with P_(4) and alcohols has been developed.With the use of copper(Ⅱ)as the catalyst and air as the safe oxidant,structurally sophisticated α-aminophosphonates have been prepared in high yields.Furthermore,this method is also suitable for selective construction of P-O-P compounds.The reaction is characterized by a complete conversion of P_(4).The activation of P_(4) with transition metals often leads to formation of complexes[M_(x)P_(y)]_(n) associated with the deactivation of transition metals.This breakthrough showcases the potential of transition-metal-catalyzed reactions in elemental phosphorus chemistry.

Aminated Cyclopropylmethylphosphonates as Potent Prostate Cancer Inhibitors

Inspired by the anti-pancreatic promising results of our novel aminated cyclopropylmethylphosphonate compounds, an in vitro anti-prostate cancer activity exploration of these compounds was carried out on human prostate cancer cell line PC-3, and showed potent inhibiting activity at low micromolar concentrations (with an IC50 of approximately 45 μM).

A Facile Synthesis of N-Substituted Spirocyclic Diester of α-Aminophosphonic Acid

A simple and direct method for preparation of N-substituted spirocyclic dieSter of □-amino phosphonic acid (4) in high yield is introduced. The reaction consists of the threecomponent reachon of phenylurea (1), an aromatic aldehyde (2), and 3,9-dichloro-2,4,8,10-tetraoxa- 3, 9 -diphosphaspiro [5,5] undecane (3) in anhydrous benzene.

喹唑啉氨基膦酸酯衍生物合成及抗菌活性

以4-氯喹唑啉、对巯基苯胺、取代醛、亚磷酸二烷基酯为原料,在无溶剂的条件下合成了18个喹唑啉氨基膦酸酯类化合物(Ⅵa~Ⅵr)。该方法产率高(72~88%)、反应操作简单、对环境友好。初步的生物活性测试结果表明:目标物在50μg·mL^(-1)时对马铃薯晚疫病菌(Phytophthora infestans)、苹果腐烂病菌(Valsa mali var.mali)、辣椒枯萎病菌(Fusarium oxysporum)、猕猴桃腐烂病菌(Sclerotinia sclerotiorum)四种病原性真菌具有一定的抑制活性,其中,化合物Ⅵl对四种病菌的抑制活性分别为89.4%、82.4%、85,7%、91.2%,优于对照药剂嘧霉胺的对四种病菌的抑制活性(72.3%、78.3%、81.9%、82.4%)。此外,化合物还显示出一定的抗细菌活性,化合物Ⅵj和Ⅵl对猕猴桃溃疡病菌(Pseudomonas syringaepv.Actinidiae,Psa)和柑橘溃疡病菌(Xanthomonas citripv.Citri)两种病菌抑制活性优于对照药剂叶枯唑。

Aminated (Cyclopropylmethyl)Phosphonates: Synthesis and Anti-Pancreatic Cancer Activity

Buoyed by the extensive research on the wide-range biological activities of aminophosphonates, a novel class of aminated (cyclopropylmethyl)phosphor-nates compounds was synthesized from diethyl ((1-(3-chloropropyl)cyclopropyl)methyl)phosphonate and various amines in the presence of Hunig’s base. Upon biological activity screening these compounds demonstrated encouraging anti-pancreatic cancer properties at low micromolar concentrations.

一种手性β-氨基膦酸酯的合成方法研究

合成了4种金鸡纳碱衍生的手性相转移催化剂,用于催化(2-氧代丙基)膦酸二甲酯与α-氨基砜的不对称Mannich反应制备β-氨基膦酸酯.经过反应条件的优化,确定了-40℃,以化合物D为催化剂,甲苯为溶剂,6%LiOH水溶剂为碱的最佳反应条件,手性β-氨基膦酸酯衍生物的收率达到90%,ee值达到60%.

新型光学活性α-氨基膦酸及其酯合成进展

α 氨基膦酸酯是一类很重要的天然氨基酸类似物 ,具有新颖的化学结构和多种生理活性 .综述了近年来光学活性α 氨基膦酸及酯的合成进展 .

新型含氟α-氨基膦酸酯的合成和晶体结构

利用含氟苯基亚胺与亚磷酸酯反应 ,合成了新型含氟α 氨基膦酸酯 ,通过元素分析、红外光谱、质谱、核磁共振氢谱对其结构进行了表征 .X射线单晶衍射测试结果表明 :化合物为三斜晶系 ,空间群P1,a =1 0 178( 6)nm ,b =1 0 3 5 4( 6)nm ,c =2 2 5 3 4( 13 )nm ,α =77 413 ( 10 )° ,β =78 3 40 ( 10 )° ,γ =77 5 40 ( 10 )° ,V =2 .2 3 3 ( 2 )nm3 ,Z =4,Dc=1 2 89Mg·m-3 ,μ =0 175mm-1,F( 0 0 0 ) =90 4 0 ,最终偏离因子R =0 0 72 8,wR =0 172 4.

N-对三氟甲基苯基-α-氨基烷基膦酸酯的合成、晶体结构及生物活性

采用活性基团拼接法将氟原子引入α 氨基烷基膦酸酯中 ,合成了一系列含氟芳基α 氨基烷基膦酸酯类新化合物 ,结构经元素分析 ,IR ,1HNMR及MS确认 .对所合成的化合物进行了抑制烟草花叶病毒 (TMV)田间生物测试 ,结果表明 ,该类化合物具有良好的抑制TMV活性 ,其中 4d化合物在 0 0 0 0 5 %浓度下对烟草花叶病毒 (TMV)防效达到了 6 7.0 3%.就此对 4d化合物作了单晶培养 ,并就晶体结构进行了X衍射分析 .结构表明 4d化合物分子属单斜晶系 ,空间群P2 1/c .晶胞参数a =1.195 7(5 )nm ,b =1.0 6 6 4(5 )nm ,c =1.5 943(7)nm ,α =90° ,β =97.6 2 3(8)° ,γ =90° ,V =2 .0 15 0 (15 )nm3 ,Z =4.Dc=1.336Mg/m3 ,μ =0 .189mm-1,F(0 0 0 ) =840 .

α-取代氨基氟代苯基膦酸酯衍生物的合成、晶体结构与抗癌活性

利用席夫碱与亚磷酸酯反应,合成了新型O,O'-二烷基-α-(6-甲氧苯并噻唑-2-基氨基)-4-氟苯基膦酸酯化合物,结构经元素分析,IR,1HNMR,13CNMR和X单晶衍射确认.X单晶衍射测试结果表明:化合物3d分子属于四面体晶系,空间群I4(1)/a,a=2.1055(3)nm,b=2.1055(3)nm,c=2.0521(5)nm,α=90.00°,β=90.00°,γ=90.00°,V=0.9098(3)nm3,Z=16,Dc=1.321mg/m3,μ=0.250mm-1,F(000)=3808.化合物还存在着1个分子内氢键[N(2)—H(2)…O(1)].生物测定表明化合物3f在20μg/mL浓度下对PC3细胞的抑制率为84.3%.

新型衍生化β-环糊精键合硅胶手性固定相的合成与性能研究

合成了苯基氨基甲酸酯全衍生化β-环糊精键合硅胶手性固定相.在正相色谱条件下,对系列2-(噻唑基)-α-氨基膦酸酯化合物进行了有效的手性拆分研究.结果表明,所有化合物都得到基线分离,对映异构体选择性α>1.2,为制备型液相色谱的手性拆分提供条件.