Solid-Phase Synthesis of 1,3,7,8-Tetrasubstituted Xanthine Derivatives on Traceless Solid Support.

نویسندگان

  • Doohyun Lee
  • Seungyeon Lee
  • Kwang-Hyeon Liu
  • Jong-Sup Bae
  • Dong Jae Baek
  • Taeho Lee
چکیده

Traceless solid-phase synthesis of 1,3,7,8-tetrasubstituted xanthine (1,3,7,8-tetrasubstituted 1H-purine-2,6(3H,7H)-dione) derivatives has been developed. The solid-phase synthetic route began on a solid supported N'-cyano-N-substituted carbamimidothioate, which was prepared from cyanamide, isothiocyanate, and Merrifield resin. After N-alkylation of carbamimidothioate resin with ethyl 2-bromoacetate, an imidazole ring is introduced by Thorpe-Ziegler-type cyclization. The resulting imidazole resin is converted to 1,3,7-trisubstituted xanthine resin using sequential reactions, such as Lewis acid-catalyzed urea formation, pyrimidine ring cyclization, and N-alkylation. After oxidation of sulfides to sulfones, traceless cleavage with amine or thiol nucleophiles afforded the desired 1,3,7,8-tetrasubstituted xanthines in good purities and overall yields (eight-steps; 36 examples). This efficient solid-phase synthesis enables the incorporation of four diversity points into the preparation of the 1,3,7,8-tetrasubstituted xanthines.

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عنوان ژورنال:
  • ACS combinatorial science

دوره 18 1  شماره 

صفحات  -

تاریخ انتشار 2016