Total Synthesis of Racemic and Optically Active Compounds Related to Physostigmine and Ring-C Heteroanalogues from 3-[2?-(dimethylamino)ethyl]2,3-dihydro-5-methoxy-1,3-dimethyl-1H-indo l-2-ol

Oxindole 11, obtained on 3-[2'-(dimethylamino)ethyl]alkylation of oxindole 12, yielded, on stereoselective reduction with sodium dihydridobis(2-methoxyelhoxy)aluminate, aminoalcohol 8 (Scheme 2). The quaternary methiodide 10, obtained from 8 with Mel, gave, in nucleophilic displacements concurring with a Hofmann elimination, (+/-)-esermethole 6, (+/-)-5-O-methylphysovenol (14),(+/-)-5-O-methyl-1-thiaphysovenol (15), and (+/-)-1-benzyl-1-demethylesermethole (16). Syntheses of(+/-)-1-benzyl-1-demethylphenserine (18), (+/-)-1-demethylphenserine (19), and (+/-)-phenserine (4) from 6 and 16 are described. Optically active 8a and 8b, obtained by chemical resolution, similarly gave the enantiomers 6a and 14a-16a of the (3aS)-series (prepared earlier from physostigmine (1a)) and their (3R)-enantiomers. The anticholinesterase activity of(+/-)-4, (+/-)-18, and (+/-)-19 was compared with that of their optically active enantiomers.