Premium
Indolylglycines Backbones in the Synthesis of Enantiopure 3,3‐Spiroindolenines, Indolyl Tetracyclic Hemiaminals, and 3‐Indolyl‐maleimides Frameworks
Author(s) -
Markus Jozef,
Ferko Branislav,
Berkeš Dušan,
Moncol Ján,
Lawson Ata Martin,
Othman Mohamed,
Daïch Adam
Publication year - 2019
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201900814
Subject(s) - chemistry , enantiopure drug , stereocenter , stereoselectivity , glyoxylic acid , indole test , organic chemistry , combinatorial chemistry , stereochemistry , enantioselective synthesis , catalysis
This paper describes the synthesis of novel N ‐substituted 3‐indolylglycines (3IGs), in high yields and optical purity via three‐component Mannich reaction (3CR) of indole and free glyoxylic acid in the presence of primary and secondary aliphatic amines. By using this efficient approach, a series of racemic 3‐indolylglycines (3IGs) as well as the optically pure ( S )‐3‐indolylglycine (( S) ‐3IG) in multigram synthesis using ( R ‐1‐phenylethylamine (( R )‐α‐PEA) as chiral pool were synthetized. In parallel investigations, 3IGs were used as the starting material for the highly stereoselective synthesis of spiroindolenines bearing three controlled contiguous stereogenic centers. Despite our expectations, the N ‐chloroacetyl esters of 3IGs did not provide the expected spiroindolenine derivatives but led us to the discovery of a new methodology for the preparation of 3‐indolylmaleimides (3IMs); compounds known for their broad range of important biological and fluorescence activities.