Studies on the Syntheses of Sesquiterpene Lactones. I. Chemical Transformation of α-Santonin into Vulgarin, C4-Epivulgarin, and Arglanine

Syntheses of vulgarin, C4-epivulgarin, and arglanine are reported. An efficient conversion of 3-oxo-5αH, 4β,6β,11βH-eudesm-1-en-6,13-olide into 1-oxo-5αH,4β,6β,11βH-eudesm-2-en-6,13-olide, a key intermediate of these syntheses, was achieved by the Meerwein-Ponndorf reaction and the allylic rearrangement of the resultant 3-hydroxyl derivative followed by the Collins oxidation. Acetalization of 1-oxo-5αH,4β,6β,11βH-eudesm-2-en-6,13-olide and successive isomerization of the double bond gave 1,1-ethylenedioxy-5αH,6β,11βH-eudesm-3-en-6,13-olide regioselectevity. Oxidation of this compound with OsO4 gave 3α,4α-dihydroxy-1,1-ethylenedioxy-5αH,6β,11βH-eudesman-6,13-olide, 3α,4α-dihydroxy-1-oxo-5αH,6β,11β-eudesman-6,13-olide and 3β,4β-dihydroxy-1,1-ethylene-dioxy-5αH,6β,11βH-eudesman-6,13-olide. Oxidation of 1,1-ethylenedioxy-5αH,6β,11βH-eudesm-3-en-6,13-olide with m-chloroperoxybenzoic acid gave 3α,4α-epoxy-1,1-ethylenedioxy-5αH,6β,11βH-eudesm-6,l3-olide stereoselectively in a quantitative yield. Treatment of 3α,4α-dihydroxy-1,1-ethylenedioxy-5αH,6β,11βH-eudesman-6,13-olide,3α,4α-dihydroxy-1-oxo-5αH,6β,11βH-eudesman-6,13-olide, and 3α,4α-epoxy-1,1-ethylenedioxy-5αH,6β,11βH-eudesm-6,13-olide with boiling 50% AcOH gave vulgarin. The same treatment of 3β,4β-dihydroxy-1,1-ethylene-dioxy-5αH,6β,11βH-eudesman-6,l3-olide gave C4-epivulgarin. Phenylselenenylation of 3α,4α-dihydroxy-1,1-ethylenedioxy-5αH,6β,11βH-eudesman-6,13-olide and successive syn-elimination of the resultant phenylseleno lactone gave 3α,4α-dihydroxy-1,1-ethylenedioxy-5αH,6βH-eudesm-11-en-6,13-olide, which was transformed into arglanine by treatment with boiling 50% AcOH.