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Solid‐phase organic synthesis of chiral, non‐racemic 1,2,4‐trisubstituted 1,4‐diazepanes with high σ 1 receptor affinity
Author(s) -
Fanter Lena,
Schepmann Dirk,
Wünsch Bernhard
Publication year - 2018
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201700334
Subject(s) - chemistry , moiety , reductive amination , solid phase synthesis , selectivity , alanine , alkylation , stereochemistry , combinatorial chemistry , amination , phase (matter) , amino acid , organic chemistry , catalysis , biochemistry , peptide
The aim of this work was to transfer the established chiral‐pool synthesis of 1,2,4‐trisubstituted 1,4‐diazepanes in solution on the solid phase. For this purpose, ( S )‐configured amino acids, ( S )‐alanine, and ( S )‐leucine, with a small methyl and a larger isobutyl moiety were attached to the solid support 9 by reductive amination. After five reaction steps on the solid support, the 1,4‐diazepanes ( S )‐ 19a , b were cleaved off and reductively alkylated to afford the 1,2,4‐trisubstituted 1,4‐diazepanes ( S )‐ 20a and ( S )‐ 21b , respectively. Both compounds show high σ 1 affinity and selectivity over the σ 2 subtype.