Spectroscopic studies of the interaction between phosphorus heterocycles and cytochrome P450

P450 fatty acid decarboxylase Ole T from Staphylococcus aureus(Ole TSA)is a novel cytochrome P450 enzyme that catalyzes the oxidative decarboxylation of fatty acids to yield primarily terminal alkenes and CO_(2) or minor a-andβ-hydroxylated fatty acids as side-products.In this work,the interactions between a series of cycloalkyl phosphorus heterocycles(CPHs)and Ole TSAwere investigated in detail by fluorescence titration experiment,ultraviolet-visible(UV-vis)and31 P NMR spectroscopies.Fluorescence titration experiment results clearly showed that a dynamic quenching occurred when CPH-6,a representative CPHs,interacted with Ole TSAwith a binding constant value of 15.2×104 M-1 at 293 K.The thermodynamic parameters(ΔH,ΔS andΔG)showed that the hydrogen bond and van der Waals force played major roles in the interaction between Ole TSAand CPHs.The UV-vis and31 P NMR studies indicated the penetration of CPH-6 into the interior environment of Ole TSA,which greatly affects the enzymatic activity of Ole TSA.Therefore,our study revealed an effective way to use phosphorus heterocyclic compounds to modulate the activity of cytochrome P450 enzymes.

STUDY ON THE SYNTHESIS OF A NEW TYPE OF PHOSPHORUS HETEROCYCLIC COMPOUNDS-PYRAZOLO[3,4-d]-1,3,2-DIAZAPHOSPHORIN-6-ONE

1-substituted-5-benzoylamino-4-pyrazolecarboxamides(2)were prepared by the reaction of 1-substituted pyrazolo[3,4-d]-oxazinone(1) with amines in benzene.The compound 2 was refluxed with excess LiAlH_4 in a mixture of THF and ether,one of the two carbamoyl groups in the molecule 2 was reduced selectively.As the results,1-substituted-5- benzylamino-4-pyrazolecarboxamides(3)were obtained.Compounds 3 reacted with Cl_2PPh-X,or P(NET_2)_3,producing the title compounds(4). The conditions of the reactions were studied.

Synthesis of 2-methoxy-6-oxo-1, 4, 2-diazaphosphorinane-2-oxide, A New Potential Antitumor Phosphorus Heterocycle Compound

2-methoxy-6-oxo-1, 4, 2-diazaphosphorinane-2-oxide 8, phosphorus counterpart of 2, 6-dioxopiperazine, was synthesized as antitumor agent. The new phosphorus heterocycle compound 8 is the key intermediate in the synthesis of phosphorus counterpart of bisdioxopiperazine.

SYNTHESIS OF FUSED PHOSPHORUS HETEROCYCLIC COMPOUNDS(II)

Using cation exchange resin(D72,Amberlyst-15) as catalyst, Mannich-type reaction of 5-amino-1,2,4-triazole 1, containing guanidine substructure, provides an efficient synthesis of a new kind of bicyclic P- and N-containing compounds, 6-phospha-4,5,6-trihydroimidazolo [2,3-e] 1,2,4-triazole 4.

A Convenient Method for the Synthesis of 1,3,2-Oxazaphospholidin-[3,2-a]-8-oxo-10-thio(or seleno)-[1,3,2]-benzodiazaphosphorines

A Convenient method for the synthesis of fused phosphorusheterocycle 1,3,2-oxazaphosphorin-[3.2-a]-8-oxo-10-thio(or seleno)-[1,3,2]-benzodiazaphosphorines was carried out in one pot by the reaction of Tris(diethylamino)phosphine with multifunctional compounds 2-(N-(beta or gamma-hydroxyl) alkylene) amino-benzamides 1. When PCL3 was used, only chlorinated product was obtained.

Synthesis,Crystal Structure and Cytotoxicity Evaluation of 2-Phenoxy-4H-spiro{naphtho[2,3-e][1,4,2] oxazaphosphinane-5,10-dione,1'-cyclohexane} 2-Oxide

2-Phenoxy-4H-spiro { naphtho[2,3-e] [ 1,4,2]oxazaphosphinane-5,10-dione, 1′-cyclo- hexane}2-oxide （C22H20NO5P） was synthesized by the Mannich-type reaction of 2-amino-3- hydroxy-l,4-naphthoquinone with phenyl phosphorodichloridite and cyclohexanone, and structurally characterized by single-crystal X-ray diffraction analysis. It crystallizes in monoclinic, space group P2 1/n with a = 7.9133（11）, b = 13.0269（18）, c = 19.091（3） ,A,β = 101.906（2）°, V= 1925.6（5） ,A^3, Z= 4, Mr = 409.36, Dr = 1.412 g/cm^3, F（000） = 856,μ = 0.178 mm^-1, S = 1.015, the final R = 0.0381 and wR = 0.0906 for 2718 observed reflections with 1 〉 2σ（I） and 262 variable parameters. This compound may be used as DNA-intercalator. Its cytotoxic activities were also tested in vitro on four human tumor cell lines.

Crystal Structure of 1,3-Dibenzyl-2-benzylaminothiocarbonyl-1,3,4- diazaphospholidin-5-thione-4-sulfide

The title compound, C31H30N3OPS3, crystallizes in monoclinic system, space group P21/n,with a = 11.839(7), b = 8.975(5), c = 29.15(2)? b = 100.07(1), V = 3049(3)?, Z = 4, Dc = 1.280g/cm3, Mr = 587.73, F(000) = 1232, m = 0.324mm-1, the final R = 0.0434 and wR = 0.1140 for 4787 observed reflections with I >2s(I). The title compound is a five-membered heterocycle containing a phosphorus, two nitrogen and two carbon atoms.The analysis result shows that the five-membered ring is nearly coplanar. The P(1)N(1) bond length(1.685? indicates the existence of pd?bond between N(1) and P(1) atoms of the title compound.