New selenyl linker for solid-phase synthesis of dehydropeptides

A novel linker possessing selenocyanate and masked carboxylic acid was developed for the solid-phase synthesis of dehydropeptides. This linker was used to demonstrate the synthesis of the model compound of RGD-conjugated dehydropeptide.     

Synthesis of chiral oligopeptides by means of catalytic asymmetric hydrogenation of dehydropeptides

Asymmetric hydrogenations of Ac-ΔTyr(Ac)-(S)-Ala-Gly-OMe (6), Ac-ΔTyr(Ac)-(R)-AlaGly-(S)-Phe-OMe (7), Ac-ΔPhe-NH-CH(R) CH₂-OCH₂Ph (10), HCO-ΔPhe-(S)-Leu-OMe (16), X-AA-ΔPhe-AA'-OMe (5: X ^tBOC, CBZ, CF₃CO; AA, AA' = α-amino acid), and ^tBOC-AA-ΔPhe-AA'-NH-Y (21: Y=H, NH-AA'-ΔPhe-AA-^tBOC, NHPh), catalyzed by cationic Rh complexes, [L*Rh(NBD)]⁺ClO₄ (L* = chiral diphosphine), were performed to give the corresponding chiral oligopeptides with high stereoselectivities. It was found that the nature of the N-protecting group of dehydrotripeptides (5) exerted a significant influence on the asymmetric induction as well as catalyst efficiency. The chiral centers in AA' and AA' amino acid residues in 5 were also found to have some influence on the catalytic asymmetric induction. Possible mechanism which can accommodate these effects are discussed. Asymmetric reduction of RCOCO-AA-OMe (13) via hydrosilylation was carried out to give chiral depsipeptide units. The asymmetric hydrogenation of dehydropeptides was successfully applied to the synthesis of enkephalin analogs, Ac-(R)Tyr-(R) -Ala-Gly-(S)-Phe-(S)-Leu-OMe (23) and Ac-(S)Tyr-(R) -Ala-Gly-(S)-Phe-(S)- Leu-OMe (29)     

One-step stereospecific synthesis of α,β-dehydroamino acids and dehydropeptides.

Dehydroamino acids and dehydropeptides were prepared by a one-pot reaction employing diethyl chloroposphate in the presence of sodium hydride. The reaction is stereospecific and proceeds without racemization.     

Oligosaccharide-peptide ligation of glycosyl thiolates with dehydropeptides: synthesis of S-linked mucin-related glycopeptide conjugates

A chemoselective strategy for oligosaccharide-peptide ligation is described in which alpha-thio analogues of mucin-related glycoconjugates can be readily accessed through site-selective conjugate addition of complex oligosaccharide thiolates to dehydroalanine-containing peptides. The efficiency of the ligation is highlighted by the rapid convergent assembly of thio-isosteres of the four tumor-associated carbohydrate antigens, T(N), T, ST(N), and 2,6-ST, as a pair of diastereoisomers at the newly formed cysteine stereocenter. The process proceeds in high yield and with complete retention of the alpha-anomeric configuration.     

An efficient synthesis of dehydroamino acids and dehydropeptides from O-Cbz and O-Eoc derivatives of serine and threonine

A simple and efficient method for the synthesis of dehydroamino acids from serine and threonine is reported. Various O-Cbz and O-Eoc derivatives of serine and threonine are prepared using CbzCl and EocCl, respectively, and are subjected to an anti-selective elimination on treatment with K₂CO₃ in DMF at 65 °C to afford dehydroalanine and dehydroamino butyric acid derivatives, respectively, in excellent yields. The high stability of these carbonate derivatives of serine and threonine allows their use in normal peptide synthesis as protected serine and threonine residues. Peptides synthesized by incorporating O-Cbz or O-Eoc derivatives undergo ready elimination under the reported conditions, to give the corresponding dehydropeptides in excellent yields. The reaction conditions are mild enough not to cause the racemization of other stereogenic centers present in the peptide.     

E/Z-Configurational assignment of dehydropeptides: Differential noe enhancement between the vinyl and amide protons of an α,β-dehydro amino acid derivative

The nuclear Overhauser enahancement difference technique applied to vinyl and amide protons of an α,β-dehydroamino acid derivative allows the assignment of the E or Z configuration; E-form, NOE = 26–37% and Z-form, NOE = 0%.     

Association of model peptides and dehydropeptides: N-acetyl-l-alanine- and dehydroalanine N′,N′-dimethylamides

The comparative studies on the association of Ac-ΔAla-NMe₂ and Ac-l-Ala-NMe₂ in carbon tetrachloride were performed by the analysis of their average molecular weight, dipole moments and FTIR spectra. To aid spectroscopic interpretation and gain some deeper insight into the nature of associates, the geometries of the minimum energy of the dimers of Ac-ΔAla-NMe₂ and Ac-l-Ala-NMe₂ were calculated by the B3LYP/6-31+G** method. The average molecular weight in the studied concentration range, for the ΔAla and l-Ala peptide, as determined by the osmometric method, did not exceed 1.5 and 1.2 of the monomeric mass, respectively. Accordingly, the percentage of the monomeric form (α) decreased as concentration was increased more significantly for the ΔAla analogue than for its saturated counterpart. In the studied concentrations, the dipole moment of the unsaturated compound decreases and that of its counterpart is almost constant. We identified a wider range of dimeric forms of Ac-ΔAla-NMe₂ than those of Ac-l-Ala-NMe₂. While Ac-ΔAla-NMe₂ mainly forms cyclic dimers, built of open conformers H/F, specific for α,β-dehydroamino acids, Ac-l-Ala-NMe₂ forms cyclic and linear dimers, characteristic for the usual amino acids. Ac-ΔAla-NMe₂ has a greater tendency to associate than its saturated variant, which is the result of stronger hydrogen bonds.     

List of publications of Prof. Dr. H. J. Seifert

List of publications of Prof. Dr. H. J. Seifert     

S.C.F.M.O. study of Hafner's hydrocarbons

SCF MO calculations have been made for Hafner's hydrocarbons using neglect of differential overlap after the manner ofPople andPariser andParr. ^* transitions have been calculated by a limited configuration interaction method. The results show that agreement between predicted spectra and observed spectra is quite good for the heptalene derivative and reasonably good for the pentalene derivative. It is suggested that both molecules are aromatic in contradiction to predictions by Craig's rule.

---

Zusammenfassung SCF MO-Rechnungen mit zero differential overlap nach der Methode vonPople, Pariser undParr wurden fürHafner's Kohlenwasserstoff angestellt. Mittels begrenzter Konfigurationswechselwirkung (wurden)die ^*-Übergänge berechnet, wobei die Ergebnisse im Fall des Heptalen-Derivates verhältnismäßig gut, in dem des Pentalen-Derivates jedoch nur ungefähr mit dem Experiment übereinstimmen. Darüber hinaus sprechen die Resultate im Gegensatz zur Craig'schen Regel dafür, daß beide Moleküle aromatischen Charakter haben.

---

Résumé Nous avons effectué des calculs SCF MO pour les hydrocarbures deHafner, en négligeant le recouvrement différentiel d'aprèsPople etPariser etParr. Quelques transitions ^* ont été calculées par interaction de configurations limitée. L'accord avec l'expérience est assez bon pour le dérivé de l'heptalène, et raisonable pour le dérivé du pentalène. Les deux molécules semblent être aromatiques, contrairement à la règle de Craig.

     

60th Birthday of Prof. Dr. Dr. h.c. Heino Finkelmann

This section contains news of the macromolecular community all over the world. Articles about, for example, people, projects, and market trends are welcome. Suggestions should be sent to the editorial office of the Macromolecular journals, preferably by E‐mail to macromol@wiley‐vch.de. The editorial office decides which articles will be published.     

Aromatic annelation. I. Synthesis of pyridines.

The preparation of substituted pyridines from cycloalkanones by elaboration of an aromatic ring is described.     

An E.P.R. study of peptides after U.V. irradiation

Abstract— Various peptides of Gly, Ala, Phe, Tyr, and Trp have been irradiated with U.V. light in the solid state or in frozen aqueous solution. The radicals produced were studied by E.P.R. spectroscopy at low temperature and at room temperature. Radicals seem to occur preferentially on Gly or Ala when in the C-terminal position and there is evidence for a photosensitization of these amino acids by aromatic amino acids.