The acetoacetyl group allows quantitative retention of configuration in the synthesis of a peptide (valylvaline methyl ester) when suitable condensing agents such as dicyclohexylcarbodi-irnide alone or in the presence of N-hydroxysuccinimide are used, and hydroxylamine hydrochloride in an acidic medium is the cleavage agent.

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Durch Umsetzung von Aminosäuren (I) mit Diketen in Gegenwart von NaOH werden die N‐Acetoacetylaminosäuren (II) erhalten, die mit Aminosäureestern (III) unter bekannten Bedingungen die ′Peptide (IV) ergeben.

Aus den N‐ bzw. O‐heterocyclischen Trionen (I), (IV), (VI) und (VIII) wurden durch Kondensation (bei unterschiedlichen Bedingungen, meist in EtOH oder wäßrigem NaHCO3) mit den Aminen (II) (L‐Alanin‐ethylester und Glycinethylester als Hydrochlorid; Glycin, Isopropylamin und Anilin direkt) die β‐Aminoendione (III), (V), (VII) und (IX) dargestellt.

Z-Thr-Gly-OR and Z-Ser-Gly-OR are oxidized by different oxidizing agents, yielding the corresponding P-carbonyl derivative and/or an a-hydroxy derivative, an oxamide, and a dimeric ester of aminomalonic acid. lnterconversions among oxidation products by different reagents have been observed.The chemical oxidation of serine and threonine in oligopeptides or related derivatives has attracted much interest. For example, (i) N-acylserine derivatives react with Pb(OAc),, undergoing C(2)-C(3) bond fission, to yield 2-acylaminoglycolic acid derivatives [cJ: Scheme, compound (S)]; (ii) serine derivatives react with Br, or HC03H to undergo P-elimination, followed by selective fragmentation; (iii) 2-serine or Z-threonine methyl ester are converted by excess of CrO, in pyridine into an oxamate deri~ative.~ The last report emphasises the oxidative C-C bond fission, and points out that 'the aminoacid literature contains remarkably little information on the oxidation of serine and threonine side-chains to the ketonic level.' In contrast, we previously reported that protected seryl and threonyl peptides are oxidized by DMSO-DCC-H3P0, to pcarbonyl derivatives which allow chemical, stereochemical, and isotopic modifications. Further studies on the stepwise oxidation of serine and threonine may allow some comparison with the oxidation occurring in vivo, and afford 'anomalous peptides' suitable for structure-activity and conformational studies.Further Studies with DMSO-DCC-H,P0,.5-A model threonyl peptide (1) affords a P-carbonyl derivative (3) in almost quantitative yield, whereas a seryl peptide (2) affords a formyl derivative (4) only in 50% yield.4 In competitive experiments, mixtures of Z-Thr-Gly-OEt (1 b) and Z-Ser-Gly-OEt (2b) were treated with increasing concentrations of the oxidizing system. At low concentrations, serine is oxidized faster than threonine, in line with the behaviour of primary alcohols, which are oxidized faster than secondary ones.' However, sufficient amounts of the oxidant lead to the above reported yields of each P-carbonyl derivative, since the serine substrate is involved in a hemiacetalization reaction which yields a compound of structure (5). In order to increase the oxidation of serine, different alcohols were added to the reaction mixtures in the expectation that they would afford the corresponding hemiacetals. However, primary alcohols competed for the oxidizing system to give aldehydes, without improving the yields of the formyl derivative (4), and t-butyl alcohol, rather unexpectedly, inhibited the oxidation of seryl peptides at all concentrations studied (1-10~). (Experimental details are omitted for brevity.)The bulk of our results indicates that a hemiacetal(5) is the most representative species of an equilibrium mixture of a formyl derivative (4), its enol tautomer, and unoxidized substrate (see also below). t Amino acids have the L-configuration, unless otherwise stated. Abbreviations used: DCC = dicyclohexylcarbodi-imide; DCU = dicyclohexylurea; DMSO = dimethyl sulphoxide; OEt = ethyl es...