SYNTHESIS OF BIOACTIVE COMPOUNDS FROM ABUNDANT NATURAL PRODUCT .13. THE SYNTHESIS AND ANALGESIC PROPERTIES OF NEW SPIROISOCHROMANYL ACID-DERIVATIVES SYNTHESIZED FROM NATURAL SAFROLE

We describe in this paper the synthesis of a new spiro[2-carboxycyclopentane-1,1-(6,7-methylenedioxy)isochroman] and a spiro[2-carboxycyclohexane-1,1-(6,7-methylenedioxy)isochroman] acids 11 and 12, obtained from natural safrole (7), isolated from sassafras oil. These derivatives were obtained in high overall yield using a synthetic route in which was observed brevity and appreciable diastereoselectivity in the intramolecular regioalkylation of the 6-position of the aromatic system of the natural starting material, the key step of the synthetic route representing a variable in the well-known Friedel-Crafts reaction. The new acids, derivatives 11 and 12, were obtained in ca 74% and 78% overall yield. They show a good analgesic profile in the pharmacological assay, the test in mice abdominal contortion.