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

✍ Scribed by Xue-Feng Pei; Nigel H. Greig; Judith L. Flippen-Anderson; Sheng Bi; Arnold Brossi

• Book ID: 102858646
• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: German
• Weight: 665 KB
• Volume: 77
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19940770519

✦ Synopsis

Abstract

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.