threo-β-Hydroxyaspartyl dipeptides

Abstract

Some dipeptides of threo-P-hydroxyaspartic acid were synthesised, by use of a-benzyl N-benzyloxycarbonyl-threo-P-hydroxyaspartate, with carbodi-imides as condensing agents.Jerusalem, Israel THE synthesis of peptides containing amino-acids with an alcoholic hydroxy-group , such as serine or threonine , presents certain difficulties due to the reactivity of the hydroxy-group, the lability of the peptide bonds (in the case of serine l), and the tendency for p-elimination reactions and N-0 (or 0-N) acyl shifts.2 Further complications are encountered in the synthesis of peptides containing the p-hydroxyaspartic acids ; these possess an additional carboxy-group which makes them tetrafunctional. Only the erythro-form of phydroxyaspartic acid has been isolated from natural sources,3 but both the threo-and erythro-isomers, first synthesized by Dakin,4 can now be prepared stereospecifically. 6 We have attempted to synthesise dipeptides containing the threo-isomer, with a view to preparing the p-hydroxy-L-aspartyl analogue of the physiologically active oligopeptide angiotensin I1 , an octapeptide with L-aspartic acid at its N-terminal end. We first used the more readily available racemic form to test the methods and then the L-isomer, obtained by resolution of N-benzyl-threo-p-hydroxy-DL-aspartic acid with L-ephedrine.6The synthesis of peptides containing hydroxy-aminoacids does not necessarily require protection of the hydroxy-group. On the contrary, the use of acyl groups for this purpose increases the possibility of p-elimination. Etherification does not suffer from this disadvantage, but the benzyl ethers cannot be prepared readily from the hydroxy-amino-acids themselves. The hydroxygroup was therefore not protected in this work.One of the classical methods for the production of CCand P-aspartyl peptides is based on the cyclic anhydride obtained when N-benzyloxycarbonylaspartic acid reacts with acetic anhydride.' This procedure , when applied

Investigation of the active site of oligosaccharyltransferase from pig liver using synthetic tripeptides as tools

“…Racemic threo/erythro-/3-hydroxyasparagine D/L-Threo-and erythro-fl-hydroxyaspartic acid were prepared from cis-and trans-epoxysuccinic acid respectively by treatment with concentrated NH40H as described previously [17]. The ,carboxy function was esterified with benzyl alcohol and the isolated fl-benzyl ester, after crystallization from water, converted into the fl-acid amide by treatment with 25 % NH40H as detailed in [18]. Crystallization from hot water yielded a racemate of D/L-threo-and erythro-fl-hydroxyasparagine respectively.…”

Rapid Synthesis ofα,β-Didehydroaspartic-Acid Derivatives Carrying aβ-Substituent

“…3 : 1. A specific preparation for the ( E )-isomer has been reported only once [9]; it involves an intermediate aminomaleic anhydride [13]. The present methodology also produces a maleic-anhydride derivative, but with a more versatile substitution.…”

“…Accordingly, facile synthetic access to these structures would be useful. While a number of general routes to didehydroamino acids have been described [1], published routes to 2,3-didehydroaspartic-acid derivatives include only 2,3-elimination from 3-hydroxyaspartic-acid esters [9] [11] or anhydrides [13] and Wittig-Horner olefination after condensation of N-acyl-2-[bis(alkyloxy)phosphinyl]glycine esters with an alkyl glyoxylate [12] [14] [15]. Two Japanese patents [16] claim a synthesis of 3-substituted 2,3-didehydroaspartic-acid esters by Ti-, Sn-, or Zn-mediated coupling reactions, but no further reports on this method have appeared.…”