High yielding selective access to spirocyclopropanated 5-oxopiperazine-2-carboxylates and 1,4-diazepane-2,5-diones from methyl 2-chloro-2-cyclopropylideneacetate.
The 2-spirocyclopropanated methyl 5-oxopiperazine-2-carboxylate and the 3-spirocyclopropanated 6-chloro-1,4-diazepane-2,5-dione could both be prepared at choice in 93 and 88% yield, respectively, from methyl 2-chloro-2-cyclopropylideneacetate () in a sequence of Michael addition of 3-benzyloxypropylamine, peptide coupling with N-Boc-glycine, Boc-group removal and cyclization. Transformation of the benzyloxypropyl side chain, peptide coupling with N-Boc-(S)-asparagine, deprotection and repeated cyclization led to the octahydro[2H]pyrazino[1,2-a]pyrazinetrione scaffold containing a rigidified mimic of a tripeptide with a DGR motif. The overall yield of after deprotection of (a total of 13 steps in 8 distinct operations) was 30%.
Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstrasse 2, D-37077, Göttingen, Germany.
Michael
M
Limbach
Vadim S
VS
Korotkov
Mazen
M
Es-Sayed
Armin
A
de Meijere
D000085:Acetates / Q000737:chemistry*; D020816:Amino Acid Motifs; D002264:Carboxylic Acids / Q000737:chemistry*; D003521:Cyclopropanes / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry; D013141:Spiro Compounds / Q000737:chemistry*; D013379:Substrate Specificity
D000085:Acetates; D002264:Carboxylic Acids; D003521:Cyclopropanes; D007659:Ketones; D009842:Oligopeptides; D013141:Spiro Compounds; C533264:methyl 2-chloro-2-cyclopropylideneacetate; C047981:arginyl-glycyl-aspartic acid; C030797:cyclopropane