Novel Synthetic Route to a-Aminophosphonates Containing Benzothiazole Moiety

A novel and efficient synthetic route to a-aminophosphonates containing benzothiazole moiety via a cascade three-component reaction from conveniently available starting materials has been developed. The target compounds 3a-3g, 7 and 8a, 8b were evaluated for their anticancer activities against the cancer cell line HL-60 in vitro by the MTT method. Compound 3g showed good cancer inhibitory activity against the tested cell line. Further study is necessary to find out the potential antitumor activities.

Synthesis,Crystal Structure and Herbicidal Activity of O,O'-Diethyl-N-[2-(5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yloxy)-benzoxyl]-1-amino-benzyl phosphonate

The crystal structure of the title compound （C25H28N5O5P,Mr=509.49） has been determined by single-crystal X-ray diffraction.The crystal is of monoclinic,space group P21/c with a=13.0726（4）,b=13.4513（4）,c=15.103（1）,β=93.650（1）°,V=2650.29（14）3,Z=4,Dc= 1.277 g/cm3,F（000）=1072,μ（MoKα）=0.147 mm-1,the final R=0.0748 and wR=0.1956 for 3186 observed reflections （I 〉 2σ（I））.The fused triazolopyrimidine system ring is coplanar,the dihedral angles between the triazolopyrimidine and C（1）-C（3）-C（5） phenyl,the triazolopyrimidine and C（17）-C（19）-C（21） phenyl,and the two phenyl rings are 66.87,58.79 and 80.11o,respectively.Intramolecular N（5）-H（5A）…O（3） and intermolecular C（2）-H（2）…N（4）,C（18）-H（18）…O（3）,C（19）-H（19）…O（2） and C（24）-H（24C）…N（4） hydrogen bonds together with C-H…π interactions contribute to the stability of the structure and result in a three-dimensional framework.The preliminary bioassay indicates that the title compound exhibits moderate herbicidal activity against dicotyledonous plants （Brassica campestris L） at the concentration of 100 mg/L.

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.

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.

Synthesis and structure-activity relationships study ofα-aminophosphonate derivatives containing a quinoline moiety

Two series of a-aminophosphonate derivatives containing a quinoline moiety have been designed and synthesized by introducing bioactive quinoline scaffold to a-aminophosphonate. The in vitro cytotoxic activities of target compounds were first investigated against two human cancer cell lines including Eca109 and Huh7 by MTT assay. Results revealed that most of target compounds exhibited moderate to high antitumor activities against the tested cancer cell lines and some demonstrated more potent inhibitory activities compared with Sunitinib. Among them, compounds 4b2 and 4b4 containing methylsubstituted aniline group were found to be more active than Sunitinib against both of two cancer cell lines, with IC50 in the range of 2.26 mmol/L–7.46 mmol/L.

Hydrophosphonylation of Aldimines under Catalysts-Free Conditions

Trimethylsilyl phosphite reacted with aldimines efficiently under catalysts-free conditions, giving a-aminophosphonates in good to excellent yields. Furthermore, the reaction can be scaled-up easily and the high yield can be maintained.

[BMIM]CI Catalyzed One-Pot Synthesis of a-Aminophospho- nate Derivatives Containing a 4-Phenoxyquinazoline Moiety under Microwave Irradiation

[BMIM]Cl catalyzed three component Mannich-type reaction of 4-（quinazolin-4-yloxy）benzenamine and aldehyde with dialkyl phosphite under microwave irradiation has been described. The salient features of the reaction leading to new a-aminophosphonates include shorter reaction time and good yields. The method is environmentally friendly and does not require toxic catalysts or solvents. To the best of our knowledge, this is the first report for [BMIM]Cl induced one-pot synthesis of a-aminophosphonate derivatives.

Camphor-derived thioureas: Synthesis and application in asymmetric Kabachnik-Fields reaction

A series of camphor-derived thiourea organocatalysts 3a–f were designed and synthesized from（1R,3S）-camphoric acid 1 and applied to the one-pot three-component Kabachnik–Fields reaction. Catalyst 3c was found to be an efficient organocatalyst for the reaction of 2-cyclopropylpyrimidin-4-carbaldehyde 4,various amines 5, and diphenylphosphite 6 to yield the corresponding enantioselective a-aminophosphonates 7a–e in 74%–82% yields and 14%–35% ee.