Synthesis of per-sulfated flavonoids using 2,2,2-trichloro ethyl protecting group and their factor Xa inhibition potential.
The synthesis of per-sulfated flavonoids, organic compounds with multiple sulfate groups, is challenging. We present here a two-step synthesis of fully sulfated flavonoids in high overall yields using the 2,2,2-trichloroethyl moiety as a protecting group. The two-step synthesis results in exclusive formation of the per-sulfated product in contrast to common sulfating agents that yield differentially sulfated mixture of compounds. Most per-sulfated flavonoids studied are activators of antithrombin for accelerated inhibition of factor Xa, a key enzyme of the blood coagulation cascade. As a group the per-sulfated flavonoids possess a range of factor Xa inhibition potential.
Gunnarsson
Gunnar T
GT
Department of Medicinal Chemistry, Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, 800 East Leigh Street, Suite 212, Richmond, VA 23219, USA.
Riaz
Muhammad
M
Adams
Joanna
J
Desai
Umesh R
UR
D002851:Chromatography, High Pressure Liquid; D065427:Factor Xa Inhibitors; D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
D065427:Factor Xa Inhibitors; D005419:Flavonoids; D015842:Serine Proteinase Inhibitors