Synthesis of tetracycline ring A analogs.

Studies directed at the synthesis of tetracycline ring A analogs are described. 4-Carbethoxycyclohexane-1,3-dione was converted to the ethyl urethan dispiro[1,3-dioxolane-2,2'-cyclohexane-4',2"(1,3)-dioxolane]-1'-carbamic acid ethyl ester via the dispiro[1,3-dioxolane-2,2'-cyclohexane-4'-2"(1,3)-dioxolane]-1'-carboxylic acid hydrazide. An improved synthesis of another cyclohexenone from methyl vinyl ketone and ethyl nitroacetate is reported. Reaction of N-(3-hydroxy-1-oxo-2-cyclohexen-4-yl)benzamide with alpha-chloroacetyl isocyanate afforded a 4(5H)-oxazolone derivative, as did the identical reaction on 5,5-dimethyl-1,3-cyclohexanedione (dimedone). This reaction provides a novel approach to these oxazolones with potential therapeutic importance. Other ring A analogs were synthesized also.