Synthetic studies on tetramic acid component of diydromaltophilin and maltophilin, and on simvastatin

Abstract

For the Synthesis of tetramic acid component of dihydromaltophilin 12 and maltophilin 13, stereoselective syntheses of tetramic acid - contained phosphonates 123a and 123b were accomplished. The key features of the scheme include the regioselective aminolysis of 2,3-epoxy alcohols 76a and 76b, and stereoselective Dieckmann cyclization to afford tetramic acids. Aminolysis of 2,3-epoxy alcohols 76a and 76b proceeded smoothly with titanium cation - mediated ring opening. Dieckmann cyclization of amides 122a and 122b was achieved using tetrabutylammonium fluoride. A synthetic modification of lovastatin 38 to simvastatin 42 was examined. Methylation of butyrate group in lovastatin 38 was unsuccessful. Hydrolysis of lovastatin 38 to diol 133 could be achieved with lithium hydroxide, but the reaction proceeded inefficiently in terms of chemical yield and reaction time. Diol 133 was converted into a simvastatin analogue, ester 136 via acetonide 134.