Conversion of α- and β-amyrin into ursolic and oleanolic acids respectively. A synthesis of oleanolic acid

Abstract

p-Amyrin has been converted into 3P-acetoxy-I 3-hydroxyoleanane. Photolysis of the nitrite of this alcohol and further standard transformations gave oleanolic acid lactone acetate and thence oleanolic acid. This conversion of p-amyrin into oleanolic acid represents, in the formal sense, a total synthesis of the latter.By a similar series of reactions ursolic acid has been obtained from a-amyrin. THE structures of oleanolic acid (I; R1 = R2 = H, R3 = Me) and ursolic acid (I; R1 = R3 = H, R2 = Me) were established as an integral part of earlier work1 on the structures of p-amyrin (11; R1 = R2 = H, R3 = Me) and cc-amyrin (11; R1 = R3 = H, R2 = Me), respectively. These two acids are representative of a considerable number of pentacyclic triterpenoids belonging to the a-and p-amyrin families which are oxygenated at C-28.l We now report the conversion of p-amyrin into oleanolic acid and of a-amyrin into ursolic acid. By virtue of a prior synthesis of p-amyrin,2 the former conversion also represents, in the formal sense, a total synthesis of oleanolic acid. The first step in the synthesis of oleanolic acid was the conversion of p-amyrin benzoate (3 p-benzoyloxyolean-12-ene) (11; R1 = Bz, R2 = H, R3 = Me) into 3pbenzoyloxy-12~,13-epoxyoleanane (I11 ; R1 = Bz, R2 = H, R3 = Me). Prior attempts to effect this conversion gave 3 ~-benzoyloxyoleanan-12-one as the only isolated product. This ketone was considered to arise by rearrangement of the desired epoxide (111; R1 = Bz,R2 = H, R3 = Me), and so care was taken to avoid conditions which might promote this process. P-Amyrin benzoate was treated with perbenzoic acid in chloroform a t 0"; a slow but clean, reaction occurred. Careful work-up gave the desired epoxide in high yield, accompanied by only traces of 3 p-benzoyloxyoleanan-12-one.

Synthesis of Norhydroperoxides from Natural Triterpenic Acids

“…276-279°C (solvate with 1 molecule of EtOH according to 1 H NMR) and [α] 22 +59.8 (c 2.24, pyridine) (ref. 4 gives m.p. 278-280°C (MeOH) and [α] D +76.8 (c 0.6); ref.…”

Reactions of Ring C in Glycyrrhetic Acid Derivatives

“…Methyl olean-9 (11), 12(13) -diene-30-oate-3{3-yl acetate (2) Methyl glycyrrhetate (7.5 g) and sodium borohydride (7.5 g) were dissolved in 250 ml dioxane and 30 ml water. The mixture was refluxed for 18 h, a further 5 g of NaBH 4 being added after 9 h. After cooling, the mixture was cautiously * An isomer of the following partial structure can formally be formed…”