SYNTHESIS OF NOVEL OPTICALLY ACTIVE CYCLIC PHOSPHOLIPID CONJUGATES OF TEGAFUR AND URIDINE STARTING FROM L-SERINE |
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Authors: | Zheng-Jie He Wen-Bin Chen Cheng-Xiang Zhang Zheng-Hong Zhou And Chu-Chi Tang |
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Affiliation: | The State Key Laboratory of Elemento-Organic Chemistry , Institute of Elemento-Organic Chemistry, Nankai University , Tianjin, 300071, P.R. China |
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Abstract: | Abstract Starting from L-serine, cyclic thiophosphoramidate conjugates (2 and 3) of Tegafur and uridine were synthesized via a multiple-step procedure of esterification, cyclic phosphorylation, and sulfurization, etc. L-serinoate was N-alkylated, then cyclized with phosphorus oxychloride, and further reacted with N3-(2-hydroxyethyl) Tegafur to afford cyclic phospholipid conjugate 4. The resultants (2, 3, and 4) were successfully separated in the form of pure diastereomer by column chromatography on silica gel. Their configurations were discussed and assigned according to their NMR spectra. The asymmetric induction effects of the carbon-based chiral centre on the diastereomer preference were also observed in these two synthetic phosphorylation cyclizations. The bioassay on their antitumor activities is under investigation. |
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Keywords: | L-serinoate Phosphorylation cyclization Phospholipid Antitumor activity |
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