Hexahydroindoline derivatives

The synthesis of lycorine-type alkaloids has received the attention of chemists as a target for exploration of new synthetic methods, because the stereoselective construction of the contiguous asymmetric centers reported until now is not always efficient. Since the previously published review (S), two investigations of the total synthesis of ( )-lycorine (1) (118), and the first total syntheses of optically active (+)-lycorine (1) and (+)-l-deoxylcorine (84) (119), the unnatural enantiomer of lycorine (1), were reported. Both of the synthetic strategies involve the construction of highly functionalized hexahydroindoline derivatives, followed by cyclization to form ring B. 

In the other synthetic route (119), Birch reduction-alkylation and transformation of functionalized hexahydroindoline derivatives constitute key reactions (Schemes 4 and 5). Birch reduction of A-(2-methoxybenzoyl)-(25)-methoxymethylpyrrolidine, followed by alkylation with 2-acetoxyethyl bromide, produced a key compound 76, azidation of which, followed by hydrolysis with acid, gave the azide 77 in 69% yield (two steps). lodolactoni-... 

Although synthetic approaches toward the montanine-type alkaloids had been made by intramolecular cyclization of 3-(3,4-methylenedioxy)phenyl-hexahydroindoline derivatives (176), these attempts were thus far unsuccessful. The 5,11-methanomorphanthridine ring systems 341-343 (Fig. 21)... 

Starting with optically active c -2-[A -cyanomethyl-A -(15-phenethyl]-l-[(3,4-methylenedioxy)phenylethynyl]cyclopentanol (365), 3-[(3,4-methy-lenedioxy)phenyl] -N- [(lS-phenethyl[hexahydroindolin-4-one (366) was synthesized in a manner similar to that noted previously. Thus, the synthesis of (-)-pancracine (339) was achieved in 25% overall yield through 366 by a sequence of reactions similar to those noted for ( )-339 (180b) (Scheme 39). Also, the same intermediate 364 employed for the synthesis of ( )-339 was transformed to ( )-desmethyl-a-isocrinamine (3 ) by way of the 3a-acetoxy derivative 367. 

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