36598-86-4

The invention discloses an amido phosphate bis-curcumin ester compound, a preparation method and application, and belongs to the field of medicinal chemistry. The compound has the structural formula as follows (referring to the description). The R1 and R2 in the formula (I) can form a saturated nitrogen heterocyclic ring structure as follows through cyclization (referring to the description). The preparation method of the compound comprises the following steps: firstly, preparing amino phosphoryl chloride or thio amino phosphoryl chloride; then reacting with curcumin to obtain the compound. The amido phosphate bis-curcumin ester compound provided by the invention has relatively good antineoplastic activity, the toxicity of the compound is smaller than that of cisplatin, and the compound can be used for preparing medicine for resisting lung cancer, stomach cancer, leukemia, breast cancer and inflammation.

Five N-(2-chloroethyl)phosphorotriamidates, (RNH)2P(O)NHCH2CH2Cl, have been synthesized, and their behavior under strongly basic conditions was studied.For N-alkyl derivatives (R = Me, PhCH2), base-promoted intramolecular displacement of chloride yielded the N-phosphorylated aziridine, (RNH)2P(O)NC2H4, as the exclusive cyclization product.For N-aryl derivatives (R = Ar), both the aziridine and the 1,3,2-diazaphospholidine, RNHP(O)NHCH2CH2NR, products could be obtained in comparable yields.The N-aromatic cyclic products are mutually interconvertible; 1,3,2-diazaphospholidines rearrange to the corresponding aziridines upon treatment with base, while bromide ions catalyze the reverse isomerization. Key words: phosphoramidates acidity, N-phosphorylated aziridines - 1,3,2-diazaphospholidines isomerization, 1,3 vs. 1,5 cyclization.

Two procedures are described for the synthesis of phenyl phosphorodiamidates in high yields.These compounds can be represented by the general formula 6 and are used for cyclisation reactions leading to phosphabarbituric acids.