Stereoselective Synthesis of 4α-Hydroxy-8,12-Guaianolides from Santonin

Abstract

Hydroxyester 2, easily obtained from santonin (1), has been transformed into 10 alpha-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 alpha-epoxide were the key steps.

Photochemische Reaktionen als Schlüsselschritte in der Naturstoffsynthese

“…[208] In deutlich besseren Ausbeuten verliefen die photochemischen Umlagerungen von Santonin-Derivaten, in denen zunächst das Lacton geöffnet wurde. Auf diese Weise wurden mehrere 4a-Hydroxy-8,12-guaianolide [209] sowie (+)-Podoandin und (+)-Zedolacton A synthetisiert. [210] Weitere Naturstoffe, die durch photochemische Umlagerungen eines Cyclohexan-anellierten Cyclohexadienons hergestellt wurden, sind (AE )-b-Vetivon, [211] (À)-Cyclocolorenon [212] und (À)-Axisonitril 3.…”

Trends in the Synthesis and Functionalization of Guaianolides

“…[39] This approach was also used by Barbosa et al in the synthesis of new α-santonin derivatives. [39] This approach was also used by Barbosa et al in the synthesis of new α-santonin derivatives.…”

Corrosion News

“…The photochemical rearrangements of santonin derivatives proceeded in distinctly better yields if the lactone moiety had first been opened. The syntheses of several 4α‐hydroxy‐8,12‐guaianolides,209 of (+)‐podoandin, and of (+)‐zedolactone A were achieved in this manner 210. Additional natural products that have been generated by photochemical rearrangement of a cyclohexane‐annulated cyclohexadienone include (±)‐β‐vetivone,211 (−)‐cyclocolorenone,212 and (−)‐axisonitrile‐3 213.…”