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Preparation of New 1,4‐Diazocanes as Scaffolds for Combinatorial Chemistry
Author(s) -
Penning Miriam,
Christoffers Jens
Publication year - 2012
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.201101645
Subject(s) - chemistry , sulfonamide , crystal structure , ring (chemistry) , derivative (finance) , urea , stereochemistry , glycine , medicinal chemistry , combinatorial chemistry , organic chemistry , amino acid , biochemistry , financial economics , economics
Hexahydro‐2‐oxo‐1,4‐diazocin‐6‐carboxylic acid constitutes a conformationally rigid, crown‐shaped scaffold. An orthogonally protected (Boc at N‐4 and methyl ester at 6‐CO 2 H) representative was prepared by ring expansion of a 3‐pyrrolidone‐derived 1,4‐diketone with MeNH 2 . After deprotection, this building block was further diversified by reductive aminations and amidations and by sulfonamide and urea formation. Furthermore, the 6‐CO 2 H function was transformed into a 6‐NHCbz group in one step by carboxamide degradation in the presence of BnOH. An example of a cyclic tripeptoidic structure was synthesized by amidation with N ‐Boc‐β‐alanine and glycine methyl ester. Structural features of the eight‐membered heterocycle were established by single‐crystal X‐ray structure analysis of a 4‐bromoaniline derivative.