New Antifungal Metabolites from the Mariana Trench Sediment-Associated Actinomycete Streptomyces sp. SY1965

New streptothiazolidine A (1), streptodiketopiperazines A (2) and B (3), and (S)-1-(3-ethylphenyl)-1,2-ethanediol (4), together with eight known compounds (5–12), were isolated from the Mariana Trench sediment-associated actinomycete Streptomyces sp. SY1965. The racemic mixtures of (±)-streptodiketopiperazine (2 and 3) and (±)-1-(3-ethylphenyl)-1,2-ethanediol (4 and 5) were separated on a chiral high-performance liquid chromatography (HPLC) column. Structures of the new compounds were elucidated by their high-resolution electrospray ionization mass spectroscopy (HRESIMS) data and extensive nuclear magnetic resonance (NMR) spectroscopic analyses. Streptothiazolidine A is a novel salicylamide analogue with a unique thiazolidine-contained side chain and its absolute configuration was established by a combination of nuclear Overhauser effect spectroscopy (NOESY) experiment, electronic circular dichroism (ECD) and 13C NMR calculations. New streptothiazolidine A (1) and streptodiketopiperazines A (2) and B (3) showed antifungal activity against Candida albicans with MIC values of 47, 42, and 42 g/mL, respectively.

Pd/C-CATALISED HYDROGENIZATION OF METHYL PYRROLE-3-CARBOXYLATES IN THE DIASTEREOSELECTIVE SYNTHESIS OF α-SUBSTITUTED β-PROLINES

The analysis of synthetic and biological importance of α-substituted β-prolines was conducted. Methods of synthesis of β-prolines and their esters, based on both intra- and intermolecular reactions of formation of functionalized pyrrolidinic cycle, as well as catalytic reduction of corresponding 2,3-substituted pyrroles and their dihydro derivatives, were systematized. The necessity of the hydrogenation process improvement of 2,3-di-substituted pyrroles using cheap catalysts was justified. The approach to α-substituted β-prolines (2-substituted pyrrolidine-3-carboxylic acids) was pro-posed, the first stage of which is N-Boc-protection of 2-substituted pyrrolidine-3-carboxylates with di-tert-butyl dicarbonate (Boc-anhydride) in the dichloromethane solution at the room temperature in presence of catalytic amounts of N,N-dime-thylaminopyridine. Obtained derivatives were subjected to hydrogenation in the autoclave at 45 atm. at 40 oC for 20 hours in presence of 10 % Pd/C catalyst. It was found, that reaction at such conditions proceeds with the full conversion of starting compounds and demonstrates high stereoselec-tivity and leads to the mixture of diastereomeric N-Boc-protected pyrrolidine-3-carboxylates of cis- and trans-configurations with corresponding contents of 84–87 % and 13–16 % according to NMR 1Н and chromato-mass spectra. The mild hydrolysis of isolated reaction mixtures in the water solution of lithium hydroxide followed by neutrali-zation and N-Boc-deprotection with 15 % hydrochloric acid allows isolating pure major diaste-reomers of α-substituted β-prolines with 69–74 % yields. Their trans-configuration was reliably confirmed by NMR 1Н spectroscopy using the NOESY experiment.

Mapping Local Conformational Landscapes of Proteins in Solution

SummaryThe ability of proteins to adopt multiple conformational states is essential to their function and elucidating the details of such diversity under physiological conditions has been a major challenge. Here we present a generalized method for mapping protein population landscapes by NMR spectroscopy. Experimental NOESY spectra are directly compared to a set of expectation spectra back-calculated across an arbitrary conformational space. Signal decomposition of the experimental spectrum then directly yields the relative populations of local conformational microstates. In this way, averaged descriptions of conformation can be eliminated. As the method quantitatively compares experimental and expectation spectra, it inherently delivers an R-factor expressing how well structural models explain the input data. We demonstrate that our method extracts sufficient information from a single 3D NOESY experiment to perform initial model building, refinement and validation, thus offering a complete de novo structure determination protocol.

Stereochemical Investigations of Diastereomeric N-[2-(Aryl)-5-methyl-4-oxo-1,3-thiazolidine-3-yl]-pyridine-3-carboxamides by Nuclear Magnetic Resonance Spectroscopy (1D and 2D)

Some new N-[2-(aryl)-5-methyl-4-oxo-1,3-thiazolidine-3-yl]-pyridine-3-carboxamides were synthesized and their structures were investigated by IR, NMR (1H, 13C, and 2D), and mass spectra. The presence of C-2 and C-5 stereogenic centers on the thiazolidinone ring resulted in diastereoisomeric pairs. The configurations of two stereogenic centers were assigned based upon 1H NMR analysis of coupling constants and 2D nuclear overhauser enhancement spectroscopy (NOESY) experiment. Resolution of the diastereoisomers was performed by high performance liquid chromatography (HPLC) using a chiral stationary phase.