ABSTRACT
An efficient synthesis of dialkylsubstituted maleic anhydrides 1a-j is described. The inhibitory potential of these original anhydride derivatives was tested toward the three human isoforms A, B and C of dual specific phosphatases Cdc25. A micromolar range inhibition of Cdc25s was observed with the maleic anhydrides bearing simple alkyl side chains longer than C(9), to reach the optimal activity with a C(17) chain length.
Subject(s)
Maleic Anhydrides/chemical synthesis , cdc25 Phosphatases/antagonists & inhibitors , Alkaline Phosphatase/antagonists & inhibitors , Alkaline Phosphatase/chemistry , Animals , Horses , Humans , Isoenzymes/antagonists & inhibitors , Isoenzymes/chemistry , Liver/enzymology , Maleic Anhydrides/chemistry , Nitrophenols/chemistry , Organophosphorus Compounds/chemistry , Structure-Activity Relationship , cdc25 Phosphatases/chemistryABSTRACT
The first and short synthesis of 16beta-hydroxy-5alpha-cholestane-3,6-dione 1 a metabolite from marine algae, has been achieved in six steps from readily available diosgenin 5. Selective deoxygenation of primary alcohol of triol 6 has been accomplished in one step using Et(3)SiH and catalytic amount of B(C(6)F(5))(3) to produce compound 9 in high yield. Oxidation of 11 with PCC, allowed the introduction of 3,6-ene-dione functionality, and further catalytic hydrogenation and deprotection furnished the 3,6-diketo steroid 1.
