139928-97-5Relevant articles and documents
Direct Synthesis of N-Protected Chiral Amino Acids from Imidodicarbonates employing either Mitsunobu or Triflate Alkylation. Feasibility Study using Lactate with Particular Reference to 15N-Labelling
Degerbeck, Fredrik,Fransson, Bengt,Grehn, Leif,Ragnarsson, Ulf
, p. 245 - 254 (2007/10/02)
Two novel approaches to N,N-diprotected chiral α-amino acid esters, based on selected imidodicarbonates as amine synthons, have been explored.Thus, N-alkylation of these substrates was smoothly accomplished by the Gabriel or Mitsunobu methods as well as by the use of triflates.Ethyl (R,S)-2-bromopropionate underwent nucleophilic substitution when treated with the potassium salt of selected imidodicarbonates in dry dimethylformamide to furnish the corresponding fully blocked (R,S)-alanines in high yield. the chirality of ethyl (S)-lactate was largely conserved when it was condensed with free imidodicarbonates and tosylcarbamates under conventional Mitsunobu conditions.The yield of the corresponding N,N-di-protected ethyl (R)-alaninate was strongly dependent of the electron-withdrawing properties of the imidodicarbonate alkyl groups.Thus, Boc2NH gave 5 percent of the product whereas Troc-NH-Z afforded the corresponding analogue in 83 percent yield under comparable conditions.On the other hand, triflates of various lactic acid esters reacted smoothly with the lithium salt of Boc2NH, also with clean inversion, as a result of which, after selective removal of two blocking groups, the N-protected alanine of opposite configuration could be isolated in high yield and excellent stereochemical purity.Both methods have been used for the synthesis of 15N-labelled N-protected (R)- and (S)-alanines, suitable for direct application to peptide synthesis.
