Michael N. Chang

Lignans with platelet activating factor antagonist activity from magnolia biondii

Abstract Six active lignans were isolated from the flower buds of Magnolia biondii . They are liroresinol-B dimethyl ether, magnolin, pinoresinol dimethyl ether, fargesin, demethoxyaschantin and aschantin. All six lignans show antagonistic activities against platelet activating factor in the [ 3 H]PAF receptor binding assay.

Neolignans from PIPER futokadsura

Abstract The structures of three new neolignans, kadsurenone, kadsurin A and kadsurin B, isolated from Piper futokadsura were determined by chemical and spectral analysis and X-ray diffraction study. Their biological activities are reported.

Total synthesis of kadsurenone and its analogs

Abstract Kadsurenone, a specific receptor antagonist of platelet-activating factor and a natural product isolated from Piper futokadsura was prepared in three steps from 3,4-dimethoxycinnamyl alcohol and allyloxyphenol via rac -(2S,3S)-5-allyl-6-hydroxy-2-(3,4-dimethoxyphenyl)-3-methyl-2,3-dihydrobenzofuran.

Synthesis of δ-lactone, oxetane and azetidinone analogs from the naturally occurring β-lactone L-659,699. The preparation of a novel HMG CoA synthase inhibitor.

Abstract A series of δ-lactone ( 1 and 2 ), oxetane ( 3 ) and azetidinone ( 4 and 5 ) analogs were prepared from the HMG CoA synthase inhibitor L-659,699 ((E,E)-11-[3′R-(hydroxymethyl)-4′-oxo-2′R-oxetanyl]-3,5,7R- trimethyl-2,4-undecadienoic acid 1,2 ), which maintained the trans relationship of the ring side chains. The N-tosyl azetidinone analog represents the first reported member of a new series of non β-lactone HMG CoA synthase inhibitors.

The inhibition of cytoplasmic acetoacetyl-CoA thiolase by a triyne carbonate (L-660,631)

The compound L-660, 631 (2-oxo-5-(1-hydroxy-2,4,6-heptatriynyl)-1,3-dioxolane-4 heptanoic acid), a natural product isolated from an Actinomycete culture, was found to inhibit rat liver cytosolic acetoacetyl-CoA thiolase, the first step in the cholesterol biosynthesis pathway, with an IC50 of 1.0 x 10(-8) M. The inhibitor had no effect on other sulfhydryl containing enzymes of lipid synthesis such as HMG-CoA synthase, HMG-CoA reductase, and fatty acid synthase. When tested in cultured human liver Hep G2 cells the compound inhibited the incorporation of 14C-acetate and 14C-octanoate into sterols 56% and 48% respectively at 3 x 10(-6) M with no effect on fatty acid synthesis. No noticeable effect was seen on fatty acid biosynthesis. This strongly suggests that the locus of inhibition of acetate incorporation into sterols found with this compound is the acetoacetyl-CoA thiolase step in the cholesterol biosynthesis pathway.

Quinones from Ardisia cornudentata

Abstract The structure of a new benzoquinone, cornudentanone, isolated from Ardisia cornudentata M . was determined.