Synthesis and taste properties of L-aspartyl-methylated 1-aminocyclopropanecarboxylic acid methyl esters

Synthesis and HPLC enantioseparation of the cyclopropane analogue of valine (c3Val)

“…The synthetic strategy for c 3 Val described by Goodman 14 and Stammer 15 involves the cyclopropanation of an a,b-dehydroalaninate (protected as the N-tert-butoxycarbonyl derivative and as the methyl or p-nitrobenzyl ester) with 2-diazopropane (Fig. 2, route a).…”

“…2, route b) would involve the addition of diazomethane to the analogous alkene moiety incorporating two methyl substituents at the b-position. The latter strategy was also envisaged by Goodman, 14 but reaction did not take place between methyl N-(tert-butoxycarbonyl)-b,b-dimethyl-a,b-dehydroalaninate and diazomethane.…”

“…In fact, the two strategies that are most generally and widely applied 10 -13 to the synthesis of Ac 3 c and its monosubstituted derivatives (i.e., addition of diazocompounds to olefins and dialkylation of glycine equivalents with 1,2-dielectrophiles) have rarely been applied to the synthesis of c 3 Val. 14,15 Thus, the reported routes 14 -30 to this cyclopropane amino acid most frequently involve the cyclization of different a-amino acid precursors bearing a leaving group at the g-position 16 -24 or the addition of sulfur 25 or phosphorus 26,27 ylides to a,b-dehydroamino acid derivatives. A Strecker-type approach 28 and the cyanide-induced ring closure of a-chloro imines 29,30 have also been applied to the preparation of c 3 Val.…”

“…This methodology affords the target compound in high yield and complements the only approach to c 3 Val involving diazocompound chemistry reported to date. 14,15 Additionally, the two enantiomers of this amino acid have been isolated in optically pure form by chromatographic resolution on a chiral column. Racemic and enantiomerically pure c 3 Val have been prepared in the N-tert-butoxycarbonyl form, which is suitable for direct use in peptide chemistry.…”

Conformational analysis of potent sweet taste ligands by NMR and computer simulations

“…[5][6][7][8][9][10][11] In sweet dipeptides the zwitterionic structure formed by the ammonium and carboxylate groups of the N-terminal residue represents the A-H and B groups of the Shallenberger and Acree glucophore hypothesis. The hydrophobic group X can either be the side chain of the second residue (type A) or an amide or ester functionality at the C-terminus of the dipeptide (type B).…”