With various model hydroxy compounds as examples, efficient procedures were developed for regioselective monophosphorylation of primary hydroxy groups in the presence of unprotected secondary hydroxy groups.Regioselective phosphorylation of primary hydroxy groups of oligo-and polyhydroxy compounds is an important problem of fine organic synthesis [1]. Development of such synthetic procedures has principle importance for efficient synthesis of such complex natural compounds as phospholipids, glycophospholipids, phosphosphingolipids, etc. Regioselective functionalization is usually achieved by choosing special conditions, e.g., reagents with sterically hindered groups capable of the preferred reaction with primary hydroxy groups, and appropriate solvents. In some cases sterically hindered amines are used. They enhance the nucleophilicity of hydroxy groups and catalyze nucleophilic substitution [2].We have shown previously that monophosphorylation of neighboring hydroxy groups is strongly complicated by the formation of intramolecular hydrogen bonds and leads mainly to diphosphorylated products [3]. However, with an excess of tertiary amines as HCl acceptors and reaction activators, monophosphorylation becomes feasible [4]. Successful monophosphorylation of diols containing free primary and secondary hydroxy groups was also attained with P(III) benzimidazolide as phosphorylating agent [5].In this study we examined more comprehensively the possibility of selective phosphorylation of primary OH groups in the presence of free secondary OH groups with some model hydroxy compounds as examples. As phosphorylating agents we chose various P(III) derivatives such as neopentylene phosphorochloridite I whose regioselectivity toward various kinds of hydroxy groups depends on the structure of tertiary amines [4] and neopentylene phosphorotriazolidite, a mild phosphorylating reagent for hydroxy groups [6]. 1,3-Butylene glycol III and 1,2-
O,O-isopropylidene-a-D-xylofuranoseIV were chosen as model compounds containing primary and secondary hydroxy groups. They are diols of different structures, i.e., an aliphatic diol and a diol with hydroxy groups on a carbohydrate matrix. The phosphorylation progress was monitored by 31 P NMR spectroscopy.The reaction of equimolar amounts of phosphorylating agent I and diol III in the presence of 10% molar excess of triethylamine proceeds nonselectively. 31 P NMR spectra show that in this case compound V P(III)-phosphorylated at the primary hydroxy groups (d P 121.9 ppm) is the major product; its molar ratio to compound VI P(III)-phosphorylated at the secondary hydroxy group (d P 128.5 ppm) is 2 : 1. To check the signal assignment in the 31 P NMR spectra, diol III was treated with 2 equiv of phosphorochloridite I to give bis-P(III)-phosphorylated compound VII. In this case, the 31 P NMR spectrum of the reaction mixture contained two signals of equal intensity at 121.9 and 128.5 ppm. After addition of sulfur, the corresponding bisthiophosphate derivative VIII was isolated pure by column chromatog...
An approach to the synthesis of amphiphilic glycophospholipids based on β cyclodextrin (β CD) was proposed. Distinctive features of the proposed method are the use of highly efficient trivalent phosphorus derivatives in the first steps of the synthesis and the regioselective monophosphorylation of nonprotected β CD. The efficiency of using 13 С NMR spectroscopy for the determination of the position and number of phospholipid residues introduced into the CD composition was shown.
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