Synthesis of a novel Boc-protected cyclopropane-modified proline analogue

The synthesis of the Boc derivative of a novel member of the cyclopropane-modified proline library, Boc-protected 5-azaspiro[2.4]heptane-6-carboxylic acid, is reported. The synthesis was performed in six steps starting from (2S,4R)-4-hydroxyproline using a modified Simmons-Smith reaction as the key step. The reaction conditions for all the steps were carefully selected to avoid racemization at the chiral centers in the intermediates and the final product.     

1-Alkyl-5-((di)alkylamino) tetrazoles: building blocks for peptide surrogates

An approach to the synthesis of 1-alkyl-5-((di)alkylamino)tetrazoles by nucleophilic substitution in 1-alkyl-5-sulfonyltetrazoles with anions generated from the primary or secondary amines was developed. Tolerance of the method to the presence of some functional groups (i.e., protected amine) in both components of the reaction was demonstrated. Obtained tetrazoles are promising building blocks for the design of peptide surrogates, in particular, for replacement approaches of alkyl urea derivatives.     

Synthesis of Boc-protected 4,5-methano-β-proline

An efficient method for the preparation of Boc-protected 4,5-methano-β-proline—a novel bicyclic cyclopropane-containing β-amino acid—was developed, starting from readily available itaconic acid. A modified Simmons–Smith reaction was used for the construction of the cyclopropane ring. The method allowed for the synthesis of both cis and trans isomers of the title compound in 49% total yield and can be employed for gram-scale preparations. An approach to the preparation of methyl 5-oxopyrrolidine-3-carboxylate, which is one of the key intermediates in the synthetic scheme, on a multigram scale was also developed.     

Electrical transport and magnetic ordering in R 2Ti3Ge4 (R=Dy, Ho and Er) compounds

New R ₂Ti₃Ge₄ (R=Dy, Ho and Er) intermetallic compounds have been synthesized and characterized by X-ray diffraction and low temperature ac magnetic susceptibility, electrical resistivity and thermoelectric power measurements were carried out. The compounds crystallize in the parent, Sm₅Ge₄-type orthorhombic structure (space group Pnma) and lanthanide contraction is observed as one moves along the rare-earth series. The changeover from paramagnetic to antiferromagnetic phase happens at low temperatures and the ordering temperature scales with the de Gennes factor. The electrical resistivity is metallic with a negative curvature above 100 K. Thermopower displays a weak maximum at temperatures less than 50 K signifying the possible phonon and magnon drag effects.     

Design,Synthesis, and Application of an Optimized Monofluorinated Aliphatic Label for Peptide Studies by Solid‐State 19F NMR Spectroscopy

A conformationally restricted monofluorinated α‐amino acid, (3‐fluorobicyclo[1.1.1]pentyl)glycine (F‐Bpg), was designed as a label for the structural analysis of membrane‐bound peptides by solid‐state ¹⁹F NMR spectroscopy. The compound was synthesized and validated as a ¹⁹F label for replacing natural aliphatic α‐amino acids. Calculations suggested that F‐Bpg is similar to Leu/Ile in terms of size and lipophilicity. The ¹⁹F NMR label was incorporated into the membrane‐active antimicrobial peptide PGLa and provided information on the structure of the peptide in a lipid bilayer.     

O-(α-Phenylethyl)hydroxylamine as a ‘chiral ammonia equivalent’: synthesis and resolution of 5-oxopyrrolidine- and 6-oxopiperidine-3-carboxylic acids

An approach to the synthesis and resolution of five- and six-membered lactams (i.e., 5-oxopyrrolidine- and 6-oxopiperidine-3-carboxylic acids) is described. The method relies on the one-pot Michael reaction—cyclization of itaconic acid or diethyl homoitaconate and enantiopure O-(α-phenylethyl)hydroxylamine as a ‘chiral ammonia equivalent’. It is shown that this chiral auxiliary can be used for the separation of diastereomeric lactam products and then easily removed by catalytic hydrogenolysis.     

Design,Synthesis, and Application of an Optimized Monofluorinated Aliphatic Label for Peptide Studies by Solid‐State 19F NMR Spectroscopy

A conformationally restricted monofluorinated α‐amino acid, (3‐fluorobicyclo[1.1.1]pentyl)glycine (F‐Bpg), was designed as a label for the structural analysis of membrane‐bound peptides by solid‐state ¹⁹F NMR spectroscopy. The compound was synthesized and validated as a ¹⁹F label for replacing natural aliphatic α‐amino acids. Calculations suggested that F‐Bpg is similar to Leu/Ile in terms of size and lipophilicity. The ¹⁹F NMR label was incorporated into the membrane‐active antimicrobial peptide PGLa and provided information on the structure of the peptide in a lipid bilayer.     

Synthesis of azabicyclo[n.1.0]alkane-derived bifunctional building blocks via the Corey–Chaykovsky cyclopropanation

An efficient approach towards the synthesis of monoprotected azabicyclo[5.1.0]octane-derived conformationally restricted γ-amino acids and diamines is reported. Optimization of the conditions for the key Corey–Chaykovsky reaction allowed the construction of two isomeric methanoazepane frameworks on a multigram scale in 55–65% yield. Additionally, the developed approach was used in the three-step synthesis of 3,4-methano-β-proline and its diamine derivatives.     

Elastic properties of the Ta–V system: bcc Ta0.33V0.67 and C15 TaV2

Resonant ultrasound spectroscopy was used to measure the elastic constants of bcc Ta_0.33V_0.67 over the temperature range 3.5–300?K; the results were compared to earlier measurements on C15 TaV₂. The temperature dependence of the polycrystalline shear modulus is completely different in the two phases; that of the bcc phase decreases with temperature whereas that of the C15 phases increases in an anomalous fashion. This difference is consistent with a model involving doubly-degenerate levels at the X point of the Brillouin zone in the C15 phase with the Fermi level lying near the doubly degenerate level. This model accounted for the unusual behaviour of the C15 phase. Debye temperatures were determined from the ultrasonic measurements: 295?K for the C15 phase and 315?K for the bcc phase.