Current progress in antifibrotics.

After years of viewing cirrhosis as the irreversible end-stage of liver fibrosis, it has been shown recently that the possibility of its reversal is no longer a dream. Several studies on experimental animal models showed possible spontaneous resolution of fibrosis after the removal of fibrogenic stimulus. Similar results were also observed in human patients with liver fibrosis due to autoimmune hepatitis and biliary etiology. However, the need for other means of treatment is urgent, especially when the removal of the causative factor is unlikely. Recent antifibrotic strategies were designed to target one or more of the three stages involved in the process of fibrosis. These are the triggering stage, fibrogenesis, and extracellular matrix accumulation. In this review, the classification of the current drugs or agents that showed inhibition of one or more of fibrosis stages with their chemical synthesis are presented.

A formal total synthesis of (-)-cephalotaxine.

A formal total synthesis of (-)-cephalotaxine (1) has been achieved. The key step is an intramolecular aldol condensation of the diketone 9, which in turn was obtained in three steps from the azabicyclic compound 6 derived from D-proline according to Seebach's procedure. Treatment of 9 with a catalytic amount of sodium 2-methyl-2-butanolate in benzene at room temperature gave the alpha, beta-unsaturated ketone 8 in 43% yield. Catalytic hydrogenation of 8 followed by reduction of the ketone 22 with sodium borohydride and acetylation of the resulting alcohol 23 gave the acetoxy derivative 24, which, after deprotection, was acylated with (methylthio)acetic acid to give the amide 26. Compound 26 was converted into optically active ketolactam 4 following the synthetic operations developed for the synthesis of the racemic compound.