Premium
Synthesis of Disubstituted Pyrazino‐Oxazine Derivatives with Controlled Stereochemistry
Author(s) -
Ručilová Veronika,
Králová Petra,
Soural Miroslav
Publication year - 2017
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.201701448
Subject(s) - chemistry , oxazines , alkylation , cleavage (geology) , stereochemistry , yield (engineering) , solid phase synthesis , pyrazine , combinatorial chemistry , organic chemistry , catalysis , peptide , biochemistry , materials science , geotechnical engineering , fracture (geology) , engineering , metallurgy
Herein, we report a simple synthesis of disubstituted pyrazino‐oxazines with controlled stereochemistry using readily available building blocks: N ‐Fmoc‐protected α‐amino acids and 2‐bromo ketones. The convenient solid‐phase synthesis afforded polymer‐supported derivatives of N ‐alkylated N ‐acylated tert ‐butylserine, which were subjected to spontaneous cyclative cleavage to yield the corresponding pyrazine intermediates. The target 1,7,8,9 a ‐tetrahydropyrazino[2,1‐ c ][1,4]oxazine‐6,9‐diones were obtained in two steps by acid‐mediated cleavage of the tert ‐butyl group followed by cyclization of the oxazine scaffold.