TOTAL SYNTHESIS OF RACEMIC AND OPTICALLY-ACTIVE COMPOUNDS RELATED TO PHYSOSTIGMINE AND RING-C HETEROANALOGUES FROM L]-2,3-DIHYDRO-5-METHOXY-1,3-DIMETHY-1H-INDOL-2-OL

Oxindole 11, obtained on 3-[2'-(dimethylamino)ethyl]alkylation of oxin dole 12, yielded, on stereoselective reduction with sodium dihydridobi s(2-methoxyelhoxy)aluminate, aminoalcohol 8 (Scheme 2). The quaternary methiodide 10, obtained from 8 with Mel, gave, in nucleophilic displa cements 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-ben zyl-1-demethylphenserine (18), (+/-)-1-demethylphenserine (19), and (/-)-phenserine (4) from 6 and 16 are described. Optically active 8a an d 8b, obtained by chemical resolution, similarly gave the enantiomers 6a and 14a-16a of the (3aS)-series (prepared earlier from physostigmin e (1a)) and their (3R)-enantiomers. The anticholinesterase activity of (+/-)-4, (+/-)-18, and (+/-)-19 was compared with that of their optica lly active enantiomers.