Reactions of Polyols with Boric Acid and Sodium Monoborate

Complex formation was studied in the systems boric acid (sodium monoborate)-polyol (D-sorbitol, mannitol, dulcitol, xylitol, glycerol)-water, concentrational stability constants of the complexes and ionization constants of bis(polyol)boric acids were estimated. In the systems D-sorbitol, D-mannitol, dulcitol, glycerol-boric acid-water electric conductivity increases sharply to peak at the molar ratio polyol : boric acid = 2 : 1; in the case of dulcitol there appears yet another peak at the molar ratio polyol : boric acid = 1 : 1. In the systems D-sorbitol, D-mannitol, glycerol-sodium monoborate-water three complex anions: [BPolyol₂]^? in acidic, [BPolyol]^?, and [B₂Poyol]^2- in neutral and basic regions of the system were revealed, their stability being dependent on the nature of the polyol and the overall concentration of the solution. In the system dulcitol-sodium monoborate-water only one complex anion [BDulc]^? is formed, and in the system xylitol-sodium monoborate-water dimeric complex [BXyl]^? is found.     

Zooxanthellamide Cs: vasoconstrictive polyhydroxylated macrolides with the largest lactone ring size from a marine dinoflagellate of Symbiodinium sp

Zooxanthellamide Cs (ZAD-Cs), C(128)H(220)N(2)O(53)S(2) (ca. 2.7 kDa), was obtained from a cultured marine dinoflagellate of the genus Symbiodinium as an inseparable isomeric mixture of polyhydroxylated 61- to 66-membered macrolides. The chemical structures of the components were clarified by detailed 2D NMR analysis to be the macrolactonized analogues of zooxanthellamide A (ZAD-A), which had been previously isolated from the same microalgae. Chemical lability of ZAD-Cs suggests that ZAD-A is an artifact derived from ZAD-Cs during the isolation steps. Three of the components possess the largest (63-, 64-, and 66-membered) ring sizes found to date among the natural macrolides. ZAD-Cs exhibited higher vasoconstrictive activity than that of the zooxanthellatoxins, the first vasoconstrictive macrolides from Symbiodinium sp. The structure-activity relationship suggests that the huge macrolactone structure is important for biological activity. The relationship between the structures of the polyol metabolites and the phylogenetic systematics of Symbiodinium sp. is also discussed.     

Bioorganic studies on marine natural products--diverse chemical structures and bioactivities

The discovery of new molecules contributes to the development of basic scientific concepts, leads to valuable drug-oriented compounds, and suggests possible new pharmacological reagents. Newly discovered substances can even be responsible for the creation of new scientific fields. Due to the radically different habitats of marine organisms, several notable examples of secondary metabolites from marine organisms have been isolated. Two of the most remarkable properties of these compounds are their structural and physiological diversities. These bioactive compounds are candidates for drugs or biological probes for physiological studies. Palytoxin is a polyol compound that shows extreme acute toxicity. Halichondrins are remarkable antitumor macrolides from sponge. Pinnatoxins, potent shellfish poisons, cause food poisoning. This paper describes bioorganic studies on such newly discovered wonders of nature. Several bioactive marine alkaloids and important substances involved in dynamic ecological systems are also described.     

Designed synthesis of cobalt and its alloys by polyol process

The role of polyol, precursor and reaction promoting agents in the synthesis of metal and alloy nanoparticles using polyol process has been investigated by analyzing the reaction steps involved in the synthesis of cobalt in Co ion-polyol-[OH⁻] ion system in detail. The reducing potential of polyols and the easiness with which any metal salt can react to form reducible complexes has been evaluated using the orbital molecular theory and the results were experimentally verified. The reduction limit of polyol and their extension using reaction promoting agents such as [OH⁻] ions is also explained. The reduction of cobalt is preceded by various reaction stages of complex/compound formation, which has been fully identified. Furthermore, the reducing form of cobalt has been identified as either cobalt alkoxide or cobalt hydroxide. The results confirmed that the complex forming reactions that take place prior to the formation of the precursor, which finally get reduced to metal, play a decisive role in determining the physical properties of the nanoparticles. The approach can be extended to reduce any metals or alloys using polyol process.     

Stereocontrolled synthesis of the C21-C38 fragment of the unnatural enantiomer of the antibiotic nystatin A1

The C(21)-C(38) fragment all-trans-41 of the unnatural enantiomer 1 of nystatin A(1) was prepared starting from the N-propionyl oxazolidinone 9. Aldol adduct ent-8 (ee > 96 %) derived in two steps was hydroborated with (thexyl)BH(2). Oxidative work-up and treatment with acid furnished delta-lactone 4. It contains the complete stereotetrade of the target molecule. The alpha,beta-unsaturated ester 28 was reached after another four steps. It should be a precursor for the polyene moieties of a variety of polyol,polyene macrolides. Illustrating that, the alpha,beta-unsaturated aldehyde 29 obtained from 28 and DIBAL was extended by 10 C atoms in four steps yielding the C(21)-C(38) segment 41. The latter set of transformations included the regio- and stereoselective Claisen rearrangement 32-->35.     

The Development of a Convergent and Efficient Enantioselective Synthesis of the Bengamides via a Common Polyol Intermediate

An efficient, general synthetic route to the bengamide family of antitumor agents from a common polyol thioester is described. Consecutive aldol condensations afford the protected polyol thioester side chain suitable for coupling to the bengamides. A novel chiral‐phase‐transfer‐catalyzed enantioselective alkylation affords the properly functionalized caprolactams required for the synthesis of more‐complex members of the bengamide family. Use of the methyl 2‐naphthyl ether protecting group, compatible with the boron Lewis acids required for enantioselective aldol condensation, allows direct access to all the bengamides.     

Synthetic mimetics of actin-binding macrolides: rational design of actin-targeted drugs

Actin polymerization and dynamics are involved in a wide range of cellular processes such as cell division and migration of tumor cells. At sites of cell lysis, such as those occurring during a stroke or inflammatory lung diseases, actin is released into the serum where it polymerizes, leading to problems with clot dissolution and sputum viscosity. Therefore, drugs that target these actin-mediated processes may provide one mechanism to treat these conditions. Marine-organism-derived macrolides, such as reidispongiolide A, can bind to, sever, and inhibit polymerization of actin. Our studies show that the function of these complex macrolides resides in their tail region, whereas the head group stabilizes the actin-drug complex. Synthetic compounds derived from this tail region could therefore be used as a mimetic of the natural product, providing a range of designer compounds to treat actin-associated diseases or as probes to study actin polymerization.     

Effects of methyl substitution on radiative and solvent quenching rate constants of [Ru(phen)2dppz]2+ in polyol solvents and bound to DNA

Methyl substituents on the distant benzene ring of the dppz ligand in the "light switch" complex [Ru(phen)(2)dppz](2+) have profound effects on the photophysics of the complexes in water as well as in the polyol solvents ethylene glycol, glycerol, and 1,2- and 1,3-propanediol. Whereas 11,12-dimethyl substitution decreases the rate of quenching by diminishing hydrogen bonding by solvent, the 10-methyl substituent in addition also decreases both the radiative and the nonradiative rate constant for decay to the ground state of the non-hydrogen-bonded excited state species. For both the 10-methyl and the 11,12-dimethyl derivatives, the effect of methyl substitution on the equilibrium of solvent hydrogen bonding to the excited state is due to changes in the entropy terms, rather than in the enthalpy, indicating that the effect is a steric perturbation of the solvent cage around the molecule. When intercalated into DNA, the effects of methyl substitution is smaller than those in polyol solvent or water, suggesting that the water molecules that quench the excited state by hydrogen bonding to the phenazine aza nitrogens mainly access them from the same groove as in which the Ru(II) ion resides. Since the Delta-enantiomer of [Ru(phen)(2)10-methyl-dppz](2+) has an absolute quantum yield of up to 0.23 when bound to DNA, a value 7000 times higher than in pure water solution, it is promising as a new luminescent DNA probe.     

Direct analysis of polyols using 3-nitrophenylboronic acid in capillary electrophoresis: thermodynamic and electrokinetic principles of molecular recognition

The design of boronic acid sensors for photometric detection of carbohydrates has relied on exploiting differences in the thermodynamic stability of complex formation for molecular recognition. Herein, we introduce a direct method for analysis of sugar alcohols using 3-nitrophenylboronic acid (NPBA) as an electrokinetic probe in capillary electrophoresis (CE). Dynamic complexation of neutral polyols by NPBA during electromigration allows for their simultaneous resolution and UV detection based on formation of an anionic ternary boronate ester complex in phosphate buffer. Unlike conventional boronic acid sensors, thermodynamic and electrokinetic processes in CE allow for improved selectivity for the resolution of sugar alcohol stereoisomers having different vicinal polyol chain lengths even in cases when binding affinity is similar due to differences in their complex mobility. Three complementary approaches were investigated to compare the thermodynamics of polyol chelation with NPBA, namely direct binding assays by CE, UV absorbance spectroscopy and an indirect pK _a depression method. Overall, CE offers a convenient platform for characterization of reversible arylboronic acid interactions in free solution while allowing for direct analysis of complex mixtures of neutral/UV-transparent polyols without complicated sample handling.     

Artificial intelligence pathway search to resolve catalytic glycerol hydrogenolysis selectivity

The complex interaction between molecules and catalyst surfaces leads to great difficulties in understanding and predicting the activity and selectivity in heterogeneous catalysis. Here we develop an end-to-end artificial intelligence framework for the activity prediction of heterogeneous catalytic systems (AI-Cat method), which takes simple inputs from names of molecules and metal catalysts and outputs the reaction energy profile from the input molecule to low energy pathway products. The AI-Cat method combines two neural network models, one for predicting reaction patterns and the other for providing the reaction barrier and energy, with a Monte Carlo tree search to resolve the low energy pathways in a reaction network. We then apply AI-Cat to resolve the reaction network of glycerol hydrogenolysis on Cu surfaces, which is a typical selective C–O bond activation system and of key significance for biomass-derived polyol utilization. We show that glycerol hydrogenolysis features a huge reaction network of relevant candidates, containing 420 reaction intermediates and 2467 elementary reactions. Among them, the surface-mediated enol–keto tautomeric resonance is a key step to facilitate the primary C–OH bond breaking and thus selects 1,2-propanediol as the major product on Cu catalysts. 1,3-Propanediol can only be produced under strong acidic conditions and high surface H coverage by following a hydrogenation–dehydration pathway. AI-Cat further discovers six low-energy reaction patterns for C–O bond activation on metals that is of general significance to polyol catalysis. Our results demonstrate that the reaction prediction for complex heterogeneous catalysis is now feasible with AI-based atomic simulation and a Monte Carlo tree search.

An end-to-end artificial intelligence framework for the activity prediction of heterogeneous catalytic systems (AI-Cat method) is developed and applied for resolving the selectivity of glycerol hydrogenolysis on Cu catalysts.     

Application of an integrated matrix-assisted laser desorption/ionization time-of-flight, electrospray ionization mass spectrometry and tandem mass spectrometry approach to characterizing complex polyol mixtures

Polyols are being used in a wide range of industrial applications including surfactants and precursors for grafted polymers. The characterization of polyols is of significance in correlating compositions and structures with their properties. We illustrate two real world examples where traditional analytical methods including GPC and NMR failed to reveal compositional differences, but the combination of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), electrospray ionization mass spectrometry (ESI MS), and MS/MS can produce compositional information required for problem solving. The first example involves failure analysis of four ethylene oxide and propylene oxide (EO/PO) copolymer products. The results from the mass spectrometry analysis unequivocally demonstrate that one of the samples has a small variation in copolymer composition, leading to its abnormal activity. The second example is in the area of deformulation of complex polyol mixtures. Two samples displaying similar properties and activities were found to be two different polyol blends. One of the samples is a more cost-effective product. These examples demonstrate that MALDI, ESI MS, and MS/MS should be seriously considered as an integrated component of an overall polyol characterization program in product failure analysis and deformulation.     

Sound absorption behavior of flexible polyurethane foams including high molecular‐weight copolymer polyol

Noise pollution is an important issue for automotive industries. In this article, the high molecular‐weight copolymer polyol is blended in the polyol mixtures for fabricating flexible polyurethane foams to improve sound absorption efficiency. Changes of cavity size and material density of the foams are negligible by inclusion of copolymer polyol in the polyol mixture, but the closed pore ratio and specific airflow resistance increase for the copolymer polyol content higher than 20 wt% because of changes of phase separation behavior from drainage flow rate reduction that occurs with increased viscosity. Sound absorption efficiency increases with increasing copolymer polyol content up to 20 wt%, but it decreases beyond this point. The sound absorption property mainly results from the closed pore ratio, not from the cavity size. The compression strength increases with increasing copolymer polyol contents by increased amount of hard segments. Therefore, an optimum amount of high molecular‐weight polyol is recommended for enhanced sound absorption property.     

Size-controlled synthesis of highly water-soluble silver nanocrystals

We describe a modified polyol process for the synthesis of silver nanocrystals with uniform sizes ranging from several nanometers to 20 nm. The use of polyacrylic acid, in place of polyvinylpyrrolidone in the conventional polyol process, significantly limits the growth of silver nanocrystals, prevents the interparticle aggregation and fusion, and leads to a uniform population of samples with high water solubility. The size of nanocrystals can be conveniently tuned by controlling the reaction time, the concentration and chain length of the polymeric surfactants, and the reaction temperature. Uniform silver nanocrystals within sizes below 20 nm are preferred candidates over larger particles for applications where high density of optical absorption is required, for example, for photothermal conversion in cancer therapy.     

Biosensor-guided screening for macrolides

Macrolides are complex polyketides of microbial origin that possess an extraordinary variety of pharmacological properties, paired with an impressive structural diversity. Bioassays for specific detection of such compounds will be of advantage for a class-specific drug screening. The current paper describes a cell-based microbial biosensor, assigning a luminescence response to natural or chemically modified macrolides, independent from their biological activity. This biosensor is based on the coupling of the structural luciferase genes of Vibrio fischeri to the regulatory control mechanism of a bacterial erythromycin resistance operon. The bioassays is easy to handle and can be applied to various screening formats. The feasibility of the test system for natural products screening is exemplified by the isolation and characterization of picromycin from a Streptomyces species. Biosensor-guided screening for macrolides is based on macrolide-promoted expression of lux genes and induction of luminescence (independent of macrolide antibiotic activity).     

Synthesis of resorcinylic macrocycles related to radicicol via ring-closing metathesis

Novel resorcinylic macrolides, for example, 17, 24, were prepared via ring-closing metathesis as analogues of the HSP90 inhibitor radicicol.     

Development of synthetic routes to macrocyclic compounds based on the HSP90 inhibitor radicicol

Short routes are reported to novel macrolides (e.g., 9, 12, 20) related to the HSP90 inhibitor radicicol.     

Combination of a sub‐3 μm superficially porous particle packed column with charged aerosol detection for the simple and sensitive measurement of nine macrolides in human urine

Due to the lack of chromophores in many macrolides, analytical methods based on mass spectrometry and electrochemical detection coupled to liquid chromatography have been suggested to be suitable for the quantification of macrolides in complex matrices. In this study, a simple and sensitive analytical method was established for the simultaneous measurement of nine macrolides in human urine by combining a sub‐3 μm superficially porous particle packed column with charged aerosol detection. After thorough investigation of various sample preparation methods, including two liquid–liquid extraction methods and four solid‐phase extraction methods, HLB solid‐phase extraction was selected and further optimized. Absolute recovery of the optimized sample preparation method ranged from 99.5–110.2%, indicating its very high extraction/clean‐up efficiency. For chromatography, parameters influencing macrolide separation were systematically optimized, and the resulting conditions allowed baseline separation of nine macrolides within 24 min using a very simple mobile phase. The established method was validated for linearity, limit of detection, limit of quantification, absolute recovery, and precision. Based on its limit of detection (0.025–0.100 μg/mL), the method had similar or greater sensitivity than most methods based on electrochemical detection. It was found that the current method was appropriate for application to real human urine samples after drug administration.     

Actin-binding toxin "tail" wags the dog

Actin-binding marine macrolides exhibit significant structural and functional diversity. In this issue, Perrins et al. demonstrate that a long stereochemically conserved aliphatic side chain, known as the "tail", found in many of these compounds is the functional determinant of cytotoxicity (Perrins et al., 2008).     

Spongistatins: Biological activity and synthetic studies

Following the isolation from marine sponges, in 1993, of a family of related highly oxygenated macrolactones named spongistatins, altohyrtins and cinachyrolides, impressive synthetic efforts have been devoted to the synthesis of these macrolides. Their highly potent activity as cancer cells growth inhibitors combined with a fascinating and complex architecture has prompted synthetic organic chemists to develop efficient routes to these molecules. From the first total syntheses by the groups of Evans and Kishi in 1997 and 1998 which delivered milligram quantities of spongistatins/altohyrtins, further intensive studies have led to new pathways with practical solution to provide gram scale amounts of key intermediates. The present review focuses on biological properties and synthetic issues related to these marine macrolides.     

超低单醇含量聚醚基软质聚氨酯泡沫的研究

以双金属络合氰化物(DMC)为催化剂,首先制备出超低单醇含量、高分子量的聚氧化丙烯醚多元醇。用这种聚醚多元醇采用全水发泡体系合成软质聚氨酯泡沫塑料,通过物理机械性能的检测表明,用DMC聚醚多元醇比常规的PPG聚醚多元醇制备的软质聚氨酯泡沫塑料具有更优越的理化性能和开发应用价值。