Novel synthesis and anti-inflammatory activities of 2,5-disubstituted-dioxacycloalkanes

A novel stereospecific synthetic route to obtain a series of 2,5-disubstituted-dioxacycloalkanes is reported. Using an in vivo inhibition assay by monitoring xylene-induced ear edema in mice, the structure–activity relationship of the dioxacycloalkane compounds was studied, and compounds possessing high anti-inflammatory activity were identified.

In 4a: R = CH2OH; 4b: R = CH(CH3)OH; 4c: R = CH2CH2OH; 4d: R = CH2CH2CH2OH, 5a: X = CH2, R1 = CH2CH(OCH3)2, R2 = H; 5a′: X = CH2, R1 = H, R2 = CH2CH(OCH3)2; 5b: X = (S)-CHCH3, R1 = CH2CH(OCH3)2, R2 = H; 5c: X = CH2CH2, R1 = CH2CH(OCH3)2, R2 = H; 5d: X = CH2CH2CH2, R1 = CH2CH(OCH3)2, R2 = H; 7a: X = CH2, R = CH2CH(OCH3)OC2H5; 7b: X = CH2, R = 1,3-dioxapentan-2-yl-methylene; 7c: X = (S)-CHCH3, R = (2S,4S,5S)-4-methyl-5-phenylacetamino-1,3-dioxan-2-yl-methylene; 7d: X = CH2CH2, R = (2S′,5′S)-5-phenyl- acetamino-1,3-dioxacyclooctan-2-yl-methylene.Figure optionsDownload as PowerPoint slide