Solid-phase synthesis of anagrelide sulfonyl analogues

ACS Comb Sci. 2014 May 12;16(5):221-4. doi: 10.1021/co400119c. Epub 2014 Apr 23.

Abstract

Simple solid-phase synthesis of 3,10-dihydro-2H-benzo[e]imidazo[1,2-b][1,2,4]thiadiazin-2-one 5,5-dioxides is described, with Fmoc-α-amino acids and 2-nitrobenzenesulfonyl chlorides (2-NosCls) being the key building blocks. Fmoc-α-amino acids were immobilized on Wang resin and transformed to the corresponding 2-nitrobenzenesulfonamides in two steps. After reduction of the nitro group, Fmoc-thioureas were synthesized followed by cyclization of the 1,2,4-benzothiadiazine-1,1-dioxide scaffold with diisopropylcarbodiimide (DIC). Cleavage of the Fmoc protecting group followed by spontaneous cyclative cleavage gave the target products in excellent crude purity.

Keywords: 2-nitrobenzenesulfonyl chlorides; Fmoc-amino acids; anagrelide analogues; cyclative cleavage; cyclic guanidines; solid-phase synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Combinatorial Chemistry Techniques
  • Cyclization
  • Fibrinolytic Agents / chemical synthesis*
  • Fibrinolytic Agents / chemistry
  • Fluorenes / chemistry
  • Quinazolines / chemical synthesis*
  • Quinazolines / chemistry
  • Solid-Phase Synthesis Techniques
  • Sulfinic Acids / chemical synthesis
  • Sulfinic Acids / chemistry

Substances

  • Amino Acids
  • Fibrinolytic Agents
  • Fluorenes
  • N(alpha)-fluorenylmethyloxycarbonylamino acids
  • Quinazolines
  • Sulfinic Acids
  • sulfonyl chloride
  • anagrelide