Synthesis and pharmacological evaluation of a clofibrate-related tricyclic spirolactone, 5-chloro-4',5'-dihydrospiro[benzofuran-2(3H),3'(2'H)-furan]-2'-one

Abstract

The chemistry and pharmacology of the title compound, spirolactone 4, are reported. The synthesis represents a new approach to the preparation of spiro compounds. The pharmacological profiles of 4 are compared to that of clofibrate in Triton-induced hyperlipidemic, sucrose-fed, and normal Sprague-Dawley rat models. Clofibrate was effective in all animal models, but the spirolactone 4 exhibited antitriglyceridemic activity only in the Triton model. The inactivity of 4 in sucrose- and chow-fed rats could not be attributed to a resistance to hydrolysis by serum esterases. Comparative studies revealed that inhibition of hepatic HMG-CoA reductase activity may not be an index of hypocholesterolemic action in sucrose-fed rats. Additionally, only clofibrate exhibited significant changes in components of the hepatic microsomal monooxygenase system.

Synthesis of Spiro‐dihydrofuran in the Presence of a Novel and Reusable Nanocatalyst Cu (II)‐Glycerol/MCM‐41

“…In the past decade, development of general methods for the synthetic spiro‐cyclic compounds having a spiro‐dihydrofuran framework have been the hot topic for chemists in modern organic synthesis, due to their important biological activities and wide applications in pharmaceutical use, such as antitumor, antibacterial, and hypocholesterolemic activities …”

First total synthesis of the biscarbazole alkaloid oxydimurrayafoline

“…¶ In 1978, Witiak and co-workers already described the formation of a benzyl chloride by treatment of a benzylic alcohol with mesyl chloride. 19 An attempted Williamson ether synthesis by deprotonation of the hydroxymethylcarbazole 11a with sodium hydride and subsequent alkylation with chloromethylcarbazole 12a failed to provide the protected oxydimurrayafoline 13.…”