REARRANGEMENT OF METHYL 11,12-DI-O-METHYL-6,7-DIDEHYDROCARNOSATE IN BASIC-MEDIUM - EASY HEMISYNTHESIS OF MILTIRONE

Methyl 11,12-di-O-methyl-6,7-didehydrocarnosate 3, obtained from the a bundant natural product carnosol 1, undergoes an interesting rearrange ment when treated with potassium tert-butoxide in dimethyl sulfoxide t o give xy-20(10-->7)abeo-abieta-5(10),8,11,13-tetraen-20- oic acid 4, in which an additional double bond is formed between C-5 and C-10 and the carboxylic acid group has migrated from C-10 to C-7, Deprotection of the two methyl ether moieties in 4 with BBr3 allows spontaneous air oxidation and decarboxylation of the catechol derivative to give the potent benzodiazepine agonist miltirone 10. The structure of 6 has bee n unequivocally elucidated by X-ray diffraction analysis and indirect chemical correlation between 4 and 6 has been established.