ABSTRACT
A series of cycloalkyl-substituted oxo-alkanedicarboxylic acids have been prepared by the TosMIC methodology departing from haloalkyl-substituted cycloalkylcarboxylic esters. cyclopropyl derivatives showed IC(50) activity in the 0.3-1.0 microM range on the de novo incorporation of radiolabeled acetate into lipids in primary cultures of rat hepatocytes, and they showed lipid-regulating properties when tested in vivo in female obese Zucker fatty rats.
Subject(s)
Dicarboxylic Acids/pharmacology , Lipids/blood , Lipoproteins/blood , Animals , Cells, Cultured , Dicarboxylic Acids/chemistry , Hepatocytes/drug effects , Hepatocytes/metabolism , Magnetic Resonance Spectroscopy , Male , Mass Spectrometry , Rats , Rats, Sprague-DawleyABSTRACT
It is observed that mesylate 1 on exposure to Li(Ot-Bu)(3)AlH in refluxing toluene rearranges selectively to the 11-oxatricyclo[5.3.1.0(2,6)]undecane derivative 3. A similar rearrangement, leading to a bridged tricyclic ether (14 --> 5), has been used as the key to the total synthesis of furanether B (4), a naturally occurring lactarane sesquiterpene, with the readily available ketone 8 as the starting material. Completion of the synthesis of the natural product is accomplished by an annulation method based on a Pummerer-induced cyclization reaction.
