Solid-phase synthesis of anagrelide sulfonyl analogues.
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.
Department of Organic Chemistry, Faculty of Science, Institute of Molecular and Translational Medicine, University of Palacky , 771 46 Olomouc, Czech Republic.
Claire
C
McMaster
Veronika
V
Fülöpová
Igor
I
Popa
Martin
M
Grepl
Miroslav
M
Soural
D000596:Amino Acids / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D005449:Fluorenes / Q000737:chemistry; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques; D013441:Sulfinic Acids / Q000138:chemical synthesis / Q000737:chemistry
D000596:Amino Acids; D005343:Fibrinolytic Agents; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D011799:Quinazolines; D013441:Sulfinic Acids; C044255:sulfonyl chloride; C021139:anagrelide
2-nitrobenzenesulfonyl chlorides; Fmoc-amino acids; anagrelide analogues; cyclative cleavage; cyclic guanidines; solid-phase synthesis