Progress toward the synthesis of piperazimycin A: exploration of the synthesis of γ-hydroxy and γ-chloropiperazic acids

Employing Hamada’s chemistry with MAOS optimization of several steps, an expedient route to key (3S,5S)- and (3R,5R)-γ-hydroxy and (3R,5S)-γ-chloropiperazic acids, was developed en route to a total synthesis of piperazimycin A.     

Thermal degradation of deoxybenzoin polymers studied by pyrolysis-gas chromatography/mass spectrometry

The thermal degradation behavior of novel ultra-fire-resistant polymers and copolymers containing deoxybenzoin units in the backbone was studied by pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). The polymers were synthesized by the polycondensation of 4,4′-bishydroxydeoxybenzoin (BHDB) with isophthaloyl chloride (to give polyarylates), phenylphosphonic dichloride (to give polyphosphonates), and their mixtures (to give poly(arylate-co-phosphonate) copolymers). The thermal decomposition, under nitrogen conditions, of BHDB-polyarylate was characterized by a simultaneous degradation of both the bisphenolic (deoxybenzoin) and isophthalate sub-units, whereas a three-step decomposition phenomenon was observed for the BHDB-polyphosphonate. BHDB-polymers containing phosphonate groups in the backbone did not show any phosphorus-based volatile decomposition products, whereas the corresponding bisphenol A-based polyphosphonates released volatile decomposition products comprised mainly of phosphorus-containing compounds.     

Stereoselective synthesis of 3,3-diarylacrylonitriles as tubulin polymerization inhibitors

A series of 3,3-diarylacrylonitriles were synthesized stereoselectively as tubulin polymerization inhibitors for potential use in cancer chemotherapy. This synthetic route features stannylcupration and palladium-catalyzed Stille cross-coupling chemistry, allowing both E and Z isomers of 3,3-diarylacrylonitriles to be prepared in a very short sequence of reactions.     

Structure revision of spiroleucettadine, a sponge alkaloid with a bicyclic core meager in H-atoms

Our 2004 disclosure of the amino hemiketal-containing spiroleucettadine was met with keen interest by the natural products and synthetic communities. As repeated efforts to synthesize spiroleucettadine failed and questions regarding the original structure elucidation process arose, evidence mounted against the validity of the proposed structure. The low ratio of H/C in the core of spiroleucattadine complicated the original structure elucidation process. Speculation prompted a reisolation of spiroleucettadine from an untouched portion of the original Luecetta collection and a thorough analysis of analytical data. In addition, a systematic analysis of candidate structures was performed via density functional theory (DFT) calculations; a favored high scoring structure 1b was ultimately confirmed to be spiroleucettadine via X-ray analysis of crystalline spiroleucettadine and reinforced the validity of DFT calculations in structure elucidation. We present the revised structure of spiroleucettadine, a bicyclic sponge alkaloid with a scarcity of H-atoms in its core.     

Precursors to [FeFe]-hydrogenase models: syntheses of Fe2(SR)2(CO)6 from CO-free iron sources

This report describes routes to iron dithiolato carbonyls that do not require preformed iron carbonyls. The reaction of FeCl 2, Zn, and Q 2S 2C n H 2 n (Q (+) = Na (+), Et 3NH (+)) under an atmosphere of CO affords Fe 2(S 2C n H 2 n )(CO) 6 ( n = 2, 3) in yields >70%. The method was employed to prepare Fe 2(S 2C 2H 4)( (13)CO) 6. Treatment of these carbonylated mixtures with tertiary phosphines, instead of Zn, gave the ferrous species Fe 3(S 2C 3H 6) 3(CO) 4(PR 3) 2, for R = Et, Bu, and Ph. Like the related complex Fe 3(SPh) 6(CO) 6, these compounds consist of a linear arrangement of three conjoined face-shared octahedral centers. Omitting the phosphine but with an excess of dithiolate, we obtained the related mixed-valence triiron species [Fe 3(S 2C n H 2 n ) 4(CO) 4] (-). The highly reducing all-ferrous species [Fe 3(S 2C n H 2 n ) 4(CO) 4] (2-) is implicated as an intermediate in this transformation. Reactive forms of iron, prepared by the method of Rieke, also combined with dithiols under a CO atmosphere to give Fe 2(S 2C n H 2 n )(CO) 6 in modest yields under mild conditions. Studies on the order of addition indicate that ferrous thiolates are formed prior to the onset of carbonylation. Crystallographic characterization demonstrated that the complexes Fe 3(S 2C 3H 6) 3(CO) 4(PEt 3) 2 and PBnPh 3[Fe 3(S 2C 3H 6) 4(CO) 4] feature high-spin ferrous and low-spin ferric as the central metal, respectively.     

Analysis and deconvolution of dimethylnaphthalene isomers using gas chromatography vacuum ultraviolet spectroscopy and theoretical computations

An issue with most gas chromatographic detectors is their inability to deconvolve coeluting isomers. Dimethylnaphthalenes are a class of compounds that can be particularly difficult to speciate by gas chromatography – mass spectrometry analysis, because of their significant coelution and similar mass spectra. As an alternative, a vacuum ultraviolet spectroscopic detector paired with gas chromatography was used to study the systematic deconvolution of mixtures of coeluting isomers of dimethylnaphthalenes. Various ratio combinations of 75:25; 50:50; 25:75; 20:80; 10:90; 5:95; and 1:99 were prepared to test the accuracy, precision, and sensitivity of the detector for distinguishing overlapping isomers that had distinct, but very similar absorption spectra. It was found that, under reasonable injection conditions, all of the pairwise overlapping isomers tested could be deconvoluted up to nearly two orders of magnitude (up to 99:1) in relative abundance. These experimental deconvolution values were in agreement with theoretical covariance calculations performed for two of the dimethylnaphthalene isomers. Covariance calculations estimated high picogram detection limits for a minor isomer coeluting with low to mid-nanogram quantity of a more abundant isomer. Further characterization of the analytes was performed using density functional theory computations to compare theory with experimental measurements. Additionally, gas chromatography – vacuum ultraviolet spectroscopy was shown to be able to speciate dimethylnaphthalenes in jet and diesel fuel samples.     

Polydopamine‐Mediated Immobilization of Alginate Lyase to Prevent P. aeruginosa Adhesion

Given alginate's contribution to Pseudomonas aeruginosa virulence, it has long been considered a promising target for interventional therapies, which have been performed by using the enzyme alginate lyase. In this work, instead of treating pre‐established mucoid biofilms, alginate lyase is immobilized onto a surface as a preventive measure against P. aeruginosa adhesion. A polydopamine dip‐coating strategy is employed for functionalization of polycarbonate surfaces. Enzyme immobilization is confirmed by surface characterization. Surfaces functionalized with alginate lyase exhibit anti‐adhesive properties, inhibiting the attachment of the mucoid strain. Moreover, surfaces modified with this enzyme also inhibit the adhesion of the tested non‐mucoid strain. Unexpectedly, treatment with heat‐inactivated enzyme also inhibits the attachment of mucoid and non‐mucoid P. aeruginosa strains. These findings suggest that the antibacterial performance of alginate lyase functional coatings is catalysis‐independent, highlighting the importance of further studies to better understand its mechanism of action against P. aeruginosa strains.

     

A new 3-alkylpyridine alkaloid from the marine sponge Haliclona sp. and its cytotoxic activity

A new alkaloid, 3-dodecyl pyridine containing a terminal cyano group (1), was isolated from the methanol extract of an Indonesia marine sponge Haliclona sp. Its chemical structure was determined by a combination of spectroscopic methods, including 1D and 2D NMR. Bioassay results indicated that compound 1 had moderate cytotoxity against tumour cell lines A549, MCF-7 and Hela with IC₅₀ values of 41.8, 48.4 and 33.2 μM, respectively.     

Strong enantioselective self-recognition of a small chiral molecule

In the present report, we have crystallized a single enantiomer and the racemate of N-3,5-dinitrobenzoyl (DNB) leucine. In both cases, the X-ray structures show clear evidence of homochiral dimerization in the solid state. Moreover, only homochiral dimers were observed in the unit cell of the racemate, a result of solid-state enantioselective complexation. The crystal structures support a chiral recognition mechanism involving two hydrogen bonds and an offset pi-pi interaction between the DNB rings.