Influence of adsorbed anions on the dehydroxylation of synthetic goethite

The influence of surface structure on the dehydroxylation of synthetic goethite has been studied using heat-flux differential scanning calorimetry. Adsorption of various anions by goethite causes a progressive change in both the amount and environment of surface hydroxyls and this is reflected by changes in the DSC curves. These alterations indicate the importance of surface features in determining the course of dehydroxylation and further suggest that, in studies of this type of reaction, the use of synthetic products known to be free of surface contaminants could prove to be of great value in understanding dehydroxylation mechanisms.

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Zusammenfassung Der Einfluß von Oberflächenstrukturen auf die Dehydroxylierung synthetischer Goethite wurde unter Anwendung der Wärmestrom-Differential-Abtastkalorimetrie untersucht. Die Adsorption verschiedener Anione durch Goethit verursacht eine progressive Änderung sowohl der Menge als auch der Umgebung der Oberflächenhydroxyle und dies wird durch die Änderungen der DSC-Kurven wiedergespiegelt. Diese Änderungen zeigen die Bedeutung der Oberflächenbeschaffenheiten bei der Bestimmung des Verlaufs der Dehydroxylierung und weisen ferner darauf hin, daß bei Studien dieses Reaktionstyps der Einsatz synthetischer Produkte, die bekanntlich frei von Oberflächenverunreinigungen sind, sich hinsichtlich der Klärung der Dehydroxylierungsmechanismen als sehr wertvoll erweisen könnte.

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Résumé On a étudié par analyse calorimétrique différentielle (DSC) l'influence de la structure de surface sur la déshydroxylation de goethites synthétiques. L'adsorption d'anions divers par la goethite entraîne une variation progressive à la fois de la quantité et de l'environnement des hydroxyles de surface, ce qui se reflète dans les variation des courbes DSC. Ces altérations indiquent l'importance des propriétés de surface quand il s'agit de déterminer le cours de la déshydroxylation et suggèrent en outre que l'emploi de produits synthétiques connus comme étant exempts de contaminants de surface, pourrait être de grande valeur dans des études de ce type de réactions, pour comprendre les mécanismes de déshydroxylation.

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Micelle-sequestered dissociation of cationic DNA-intercalated drugs: unexpected surfactant-induced rate enhancement

Detergent sequestration using micelles as a hydrophobic sink for dissociated drug molecules is an established technique for determination of dissociation rates. The anionic surfactant molecules are generally assumed not to interact with the anionic DNA and thereby not to affect the rate of dissociation. By contrast, we here demonstrate that the surfactant molecules sodium dodecyl sulfate (SDS), sodium decyl sulfate, and sodium octyl sulfate all induce substantial rate enhancements of the dissociation of intercalators from DNA. Four different cationic DNA intercalators are studied with respect to surfactant-induced dissociation. Except for the smallest intercalator, ethidium, the dissociation rate constants increase monotonically with surfactant concentration both below cmc and (more strongly) above cmc, much more than expected from electrostatic effects of increased counterion concentration. The rate enhancement, most pronounced for the bulky, multicationic, hydrophobic DNA ligands in this study, indicates a reduction of the activation energy for the ligand to pass out from a deeply penetrating intercalation site of DNA. The discovery that surfactants enhance the rate of dissociation of cationic DNA-intercalators implies that rate constants previously determined by micelle-sequestered dissociation may have been overestimated. As an alternative, more reliable method, we suggest instead the addition of excess of dummy DNA as an absorbent for dissociated ligand.     

Total synthesis of (+)-discodermolide: an improved endgame exploiting a Still-Gennari-type olefination with a C1-C8 beta-ketophosphonate fragment

[structure: see text] An improved, third-generation, total synthesis of (+)-discodermolide, a potent microtubule-stabilizing anticancer agent of marine sponge origin, is achieved in 11.1% yield over 21 steps. Key steps include a Still-Gennari HWE olefination, performed using NaH as the base, between C1-C8 beta-ketophosphonate 7 and C9-C24 aldehyde 8, introducing the (8Z)-alkene with 10:1 selectivity, and K-Selectride reduction of the derived enone 16, installing the (7S)-configuration.     

Actin-binding marine macrolides: total synthesis and biological importance

Marine organisms produce a fascinating range of structurally diverse secondary metabolites, which often possess unusual and sometimes unexpected biological activities. This structural diversity makes these marine natural products excellent molecular probes for the investigation of biochemical pathways. Recently, a number of novel and stereochemically complex macrolides, having a large macrolactone (22- to 44-membered) ring, that interact with the actin cycloskeleton have been isolated from different marine sources. Actin, like tubulin, is a major component of the cytoskeleton and has important cellular functions. Although the details of these interactions are still under investigation, these marine macrolides are becoming increasingly important as novel molecular probes to help elucidate the cellular functions of actin. Owing to their potent antitumor activities, these compounds, for example the aplyronines, also have potential for preclinical development in cancer chemotherapy. Their appealing molecular structures, with an abundance of stereochemistry, and biological significance, coupled with the extremely limited availability from the marine sources, have stimulated enormous interest in the synthesis of these compounds. This review summarizes the biological properties of these unusual marine natural products and features the recently completed total syntheses of swinholide A, scytophycin C, aplyronine A, mycalolide A--all of these being potent cytotoxic agents that target actin--and a diastereoisomer of ulapualide A. Rather than detailing each individual step of these multistep total syntheses, the different synthetic strategies, key reactions, and methods adopted for controlling the stereochemistry are compared.     

Total synthesis of the microtubule-stabilizing agent (-)-laulimalide

[structure: see text] The total synthesis of the potent microtubule-stabilizing anticancer agent (-)-laulimalide has been achieved in 27 steps and 2.9% overall yield. Notable features are the use of Jacobsen HDA chemistry for the enantioselective construction of the side chain dihydropyran, a diastereoselective aldol coupling using chiral boron enolate methodology, a Mitsunobu macrolactonization, and a Sharpless AE to introduce the epoxide onto des-epoxy-laulimalide.     

Stereochemistry of contiguous cyclopropane formation from cascade cyclization of a skipped dienyl homoallyl triflate

Solvolysis of asymmetric homoallylic triflates bearing a terminal stannyl substituent gives disubstituted cyclopropanes and bicyclopropanes bearing differentiated termini in high enantiopurity.     

Total synthesis of polycavernoside A, a lethal toxin of the red alga Polycavernosa tsudai

[structure: see text] Two approaches to the synthesis of the aglycon 120 of polycavernoside A (1) were developed, only one of which was completed. The successful "second-generation" route assembled the aglycon seco acids 102 and 106 via Nozaki-Hiyama-Kishi coupling of aldehyde 70, prepared from methyl (S)-3-hydroxy-2-methylpropionate (72) and (S)-pantolactone (73), with vinyl bromide 71. The latter was obtained from a sequence which commenced from the silyl ether 24 of 3-hydroxypropionaldehyde and entailed cyclization of (Z)-zeta-hydroxy-alpha,beta-unsaturated ester 82. Regioselective Yamaguchi lactonization of trihydroxycarboxylic acids 102 and 106 and subsequent functional-group adjustments led to macrolactone 120, to which the fucopyranosylxylopyranoside moiety was attached. Stille coupling of the glycosidated aglycon 128 with dienylstannane 129 furnished polycavernoside A in a synthesis for which the longest linear sequence was 25 steps. The overall yield to lactone 120 was 4.7%.     

O-silylated enolate phenylthialkylation: A synthesis of α,β-unsaturated 5- and 6-membered lactones.

ZnBr₂-catalysed phenylthioalkylation of ketene bis(trimethylsilyl)acetals, obtained from carboxylic acids, with appropriate α-chlorosulphides can be used to prepare γ- and δ- lactones.     

Synthesis and biological evaluation of spongistatin/altohyrtin analogues: E-ring dehydration and C46 side-chain truncation

Simplified analogues of the potent antimitotic marine macrolide spongistatin 1/altohyrtin A were synthesised and evaluated as growth inhibitory agents against a range of human tumour cell lines, including Taxol-resistant strains, revealing that E-ring dehydration leads to enhanced cytotoxicity at the low picomolar level while truncation of the side-chain at C46 results in a drastic decrease in activity.