Stereselective Synthesis of 4-Hydroxy-8,12-Guaianolides from Santonin

[EN] Hydroxyester 2, easily obtained from santonin (1), has been transformed into 10¿-hydroxyguai-3-en-8,12-olide 6, a good intermediate for the synthesis of natural 8,12-guaianolides. Compound 6 was obtained from 2 by photochemical rearrangement of its acetyl derivative 7, stereoselective hydrogenation on Pd/C, reduction, regioselective elimination, hydrolysis, and lactonization. The synthesis of the natural guaianolides 3¿5 was carried out in two sequences in which the regioselective elimination of a hydroxyl group at C10 with triflic anhydride or SOCl2 to afford, respectively, the endo or exo double bond on C10 and the regioselective opening of the C3¿C4 ¿-epoxide were the key steps.Financial support from the European Commission (Grant FAIR CT96-1781) and from the Dirección General de Investigación Científica y Técnica (DGICYT; Grant PB 94-0985) is gratefully acknowledged. V.B. and A.M.C. are especially thankful to the Conselleria de Cultura, Educació i Ciencia (Generalitat Valenciana), and European Commission, respectively, for a grant.Blay, G.; Bargues, V.; Cardona, L.; Collado, AM.; García, B.; Muñoz Roca, MDC.; Pedro, JR. (2000). Stereselective Synthesis of 4-Hydroxy-8,12-Guaianolides from Santonin. The Journal of Organic Chemistry. 65(7):2138-2144. https://doi.org/10.1021/jo991756nS2138214465