|Budget Amount *help
¥4,100,000 (Direct Cost : ¥4,100,000)
Fiscal Year 1996 : ¥4,100,000 (Direct Cost : ¥4,100,000)
To develop new synthetic methods of cyclic peroxides, we used two methodologies. (1) Cycloaddition of carbonyl oxide intermediates, generated from alkene ozonolysis, and (2) cyclizations of the solvent-derived ozonolysis products, prepared by capture of the carbonyl oxide intermediate by protic solvent.
As the important examples of the first methodology, we discovered that (1) [3+3+2] cycloaddition between a carbonyl oxide, a nitrone, and an aldehyde provides a new 8-membered cyclic peroxide 3,4-dihydro-1,2,5,7,4-tetroxazocine derivative and (2) [3+2] cycloadditions of carbonyl oxides to imines lead to the formation of 1,2,4-dioxazolidines ; This is the most general method for the synthesis of this type of cyclic peroxides.
As the examples of the second methodology, we found that (1) ozonolysis of indene derivatives in trifluoroacetic acid provides the alpha-alkoxy-alpha'-hydroperoxy ethers, derived from partial capture of the carbonyl oxide by the adjacent aldehyde group, (2) acid-catalyzed cyclization of the derived ozonolysis product leads to the formation of 10-membered hexoxecane derivatives, while capture of the solvent-derived ozonolysis product by formaldehyde oxide, followed by acidcatalyzed cyclization results in the formation of the 8-membered pentoxocane derivative. (3) By the ozonolysis of vinyl ether in the presence of unsaturated alcohol the corresponding unsaturated hydroperoxy acetal is obtained ; Depending on the structure of the acetals, subsequent N-halosuccinimide-mediated cyclization gives the halogeno-substituted 1,2,4-trioxanes and/or 1,2,4-trioxepanes.
Using owl monkey (Aotus trivirgatus), Professor Mamoru Suzuki of Gumma University is kindly investigating the effectiveness of the prepared cyclic peroxides as the antimalarial drugs.