33 ケトスルホキサイドを利用した合成研究 : Olivacine,Ellipticine,Estroneの合成

抄録

I. Synthesis of Olivacine and Ellipticine Acid-catalyzed cyclization of β-ketosulfoxides derived from indolepropionic acid derivatives afforded tetrhydrocarbazol-2-ones. This reaction was now applied for the synthesis of antitumor indole alkaloids, olivacine (1) and ellipticine (19). Methyl indolepropionate (5) was converted with Et_2SO to a keto-sulfoxide (8) (95%), which was cyclized to a tetrahydrocarbazolone (10) (51%). To the carbonyl group in 10 butyl acetate was added in the presence of BuLi to give an adduct (11) (97%), which was converted to a carbazole-2-acetic acid derivative (13) (98%). Olivacine (1) was easily synthesized from 13 through a series of usual methods. Overall yield of 1 from 5 was 28%. Similarly, ellipticine (19) was synthesized from methyl indolebutylate (20) in 23% overall yield. II. Synthesis of Estrone Although there are so many reports on the synthsis of estrone, more practical methods are still required because of invaluable physiological properties of estrogens. Thermal elimination of β-ketosulfoxide gives αβ-unsaturated ketone. This reaction was now applied for the synthesis of key intermediates (35,36) in the Smith's estrone synthesis. A β-ketosulfoxide (30) derived from ethyl m-methoxyphenylbutyrate (29) and Me_2SO was methylated with MeI to 31 (91%). Thermal elimination of 31 gave αβ-unsaturated ketone (33), which was condensed with methylcyclopentanedione (34) to give 35. More conveniently 31 was heated in the presence of 34 in diglyme to give 35 (70%) through the elimination and Michael addition. 32 prepared from 29 and EtS(O)C_6H_5 gave directly an acid-catalyzed cyclization product (36) (37%).