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‐1 H ‐indo l‐2‐ol

Oxindole 11 , obtained on 3‐[2′‐(dimethylamino)ethyl]alkylation of oxindole 12 , yielded, on stereoselective reduction with sodium dihydridobis(2‐methoxyethoxy)aluminate, aminoalcohol 8 ( Scheme 2 ). The quaternary methiodide 10 , obtained from 8 with MeI, 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 (3a S )‐series (prepared earlier from physostigmine ( 1a )) and their (3 R )‐enantiomers. The anticholinesterase activity of (±)‐ 4 , (±)‐ 18 , and (±)‐ 19 was compared with that of their optically active enantiomers.