Enantioselective formal total synthesis of the antitumor macrolide bryostatin 7

A new enantioselective synthesis of Masamune's AB fragment (1) for bryostatin 7 is described. Key steps in the new route include a Meerwein-Ponndorf-Verley reduction to set the O(7) stereocenter and an alkylative union between the dithiane 6 and iodide 5 to construct the C(9)-C(10) bond. Because we have previously published a synthesis of Masamune's C-ring phenyl sulfone 2, our new route to 1 constitutes a formal total synthesis of bryostatin 7; it also corrects the previously reported spectral data for 1 in CDCl3.     

Synthesis of RP 48497, an impurity of eszopiclone

RP 48497 is a photodegradation product of eszopiclone, a non-benzodiazepine sedative-hypnotic used in the treatment of insomnia. We report herein the first synthesis of RP 48497 via reduction, chlorination, and recyclization of 6-(5-chloropyridin-2-yl)-7-hydroxy-6,7-dihydropyrrolo[3,4-b]pyrazin-5-one (3), a key intermediate in the synthesis of eszopiclone. The structure of RP 48497 was confirmed by its (1)H-NMR and MS data. The mechanism of the reduction step in the synthesis of RP 48497 was also studied and the key parameters were determined. These findings should be important for quality control purposes in the manufacture of eszopiclone.     

Asymmetric synthesis of (-)-tetrahydrolipstatin: an anti-aldol-based strategy

A stereoselective synthesis of (-)-tetrahydrolipstatin is described. The synthesis involves an asymmetric ester derived titanium enolate anti-aldol reaction, a nitro-aldol reaction to append the C-2' C(11) side chain, and a diastereoselective reduction of a beta-hydroxy ketone to an anti-1,3-diol functionality followed by its elaboration to (-)-tetrahydrolipstatin.     

Aromatic ortho-benzylation reveals an unexpected reductant

The discovery of a novel arylpalladium(II) reduction enables the synthesis of diarylmethanes via reductive benzylation. Benzyl chlorides were found to be the major source of hydride, acting as an alkylating agent and an aprotic surrogate for benzyl alcohol. This represents the first example of an arylpalladium(II) reduction mediated by a benzyl halide.     

The first synthesis of (-)-asperpentyn and efficient syntheses of (+)-harveynone, (+)-epiepoformin and (-)-theobroxide

A generally applicable strategy for the synthesis of a range of polyoxygenated cyclohexane natural products has been developed. The enantioselective syntheses of (-)-theobroxide, a polyoxygenated cyclohexane natural compound with potent growth inducing properties in potato microtubers has been achieved via a 1,2 O-silyl migration between trans-hydroxyl groups and a remote hydroxyl directed epoxidation of an enone derived from quinic acid. A thus derived alpha-iodoenone was subjected to Stille coupling with tetramethylstannane to afford the first title compound. A similar strategy enabled a route to the complete asymmetric synthesis of the acetylenic phytotoxin (+)-harveynone. By selective reduction of (-)-theobroxide, (+)-epiepoformin was also prepared in enantiopure form and similarly, stereoselective reduction of (+)-harveynone completed the first enantioselective synthesis of (-)-asperpentyn, another natural compound with antimicrobial activity.     

Mechanistic and kinetic studies of crystallization of birnessite

Kinetic and mechanistic features have been studied for the crystallization of birnessite in aqueous systems via different synthesis methods: the oxidation of Mn2+, reduction of MnO4-, and redox reaction between Mn2+ and MnO4-. For oxidation methods, a topotactical conversion from Mn(OH)2 to birnessite via feitknechtite (beta-MnOOH) is observed. In reduction methods, birnessite evolves from the initially produced amorphous manganese oxide (AMO gel). For redox methods, both mechanisms exist, with the latter prevailing. A liquid mechanism is proposed to describe the reduction and redox synthesis, which comprises three stages: an induction period, a fast crystallization period, and a steady-state period. The redox method is accompanied by the formation and phase transformation of feitknechtite to birnessite. A method combining IR and XRD quantitation is proposed to detect nuclei in the induction period. Crystallization rates and apparent energies of activation of crystallization for reduction and redox methods are determined.     

Platinum-catalyzed synthesis of water-soluble gold-platinum nanoparticles

The ability to control composition and size in the synthesis of bimetallic nanoparticles is important for the exploitation of the bimetallic catalytic properties. This paper reports findings of an investigation of a new approach to the synthesis of gold-platinum (AuPt) bimetallic nanoparticles in aqueous solution via one-phase reduction of AuCl(4-) and PtCl(4)(2-) using a combination of reducing and capping agents. Hydrogen served as a reducing agent for the reduction of Pt(II), whereas acrylate was used as a reducing agent for the reduction of Au(III). The latter reaction was found to be catalyzed by the formation of Pt as a result of the reduction of Pt(II). Acrylate also functioned as capping agent on the resulting nanocrystals. By controlling the feed ratios of AuCl(4-) and PtCl(4)(2-) and the relative concentrations of acrylate, an effective route for the preparation of AuPt nanoparticles with bimetallic compositions ranging from approximately 4 to 90% Au and particle sizes ranging from 2 to 8 nm has been demonstrated. The composition, size, and shell properties were characterized using transmission electron microscopy, direct current plasma-atomic emission spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. Implications of the results to the exploration of bifunctional catalysts are also briefly discussed.     

A short and efficient enantioselective route to a key intermediate for the total synthesis of forskolin

A simple route for the enantioselective synthesis of key intermediates (11 and 12) for the total synthesis of forskolin has been developed starting from acid 6 and (S)-alcohol 5. The latter is prepared by enantioselective catalytic CBS reduction of dienone 3, and is converted by an intramolecular Diels-Alder reaction to tricyclic lactone 9.     

Application of the aza-Achmatowicz oxidative rearrangement for the stereoselective synthesis of the Cassia and Prosopis alkaloid family

cis-2-Methyl-6-substituted piperidin-3-ol alkaloids of the Cassia and Prosopis species are readily prepared by a combination of an aza-Achmatowicz oxidative rearrangement and dihydropyridone reduction followed by a stereoselective allylsilane addition to a N-sulfonyliminium ion. The stereochemical outcome of the reduction reaction can be attributed to steric hindrance between the pseudoaxially oriented 2,6-substituents and the equatorially approaching hydride reagent which explains the exclusive formation of the cis-alcohol by axial approach of the hydride. The unsaturation present in the (E)-methyl-pent-3-enoate side chain was removed by catalytic reduction, and the remaining ester group was converted to the corresponding Weinreb's amide. This key intermediate was utilized for the synthesis of azimic acid, deoxocassine, cassine, and spicigerine. The facile preparation of (S)-N-tosylamidofuran 16 and its conversion to the chiral Achmatowicz oxidation product 18 provide a formal chiral synthesis of these alkaloids.     

Practical preparation of 3,3-difluoropyrrolidine

A practical and cost-effective synthesis of 3,3-difluoropyrrolidine is reported. The synthesis involves the isolation of two intermediates, which are prepared via two efficient through processes: (1) a Claisen rearrangement followed by a Ru(VIII)-catalyzed oxidation to prepare the 2,2-difluorosuccinic acid and (2) an efficient cyclization to form N-benzyl-3,3-difluoropyrrolidinone followed by BH(3).Me(2)S reduction.     

A concise formal stereoselective total synthesis of （-）-swainsonine

A short formal stereoselective synthesis of （-）-swainsonine （1） is described. Our synthesis started with the versatile building block （R）-3-benzyloxyglutarimide 5. Through controlled regioselective reduction, Ley＇s-sulfone chemistry （N-α-sulfonylation and ZnCl2-catalyzed N-α-amidovinylation）, an RCM reaction, and an amide reduction, the synthesis of unsaturated indolizidine （8R,8aS）-3 has been achieved in five steps. The indolizidine （8R,8aS）-3 is an advanced intermediate toward the synthesis of （-）-swainsonine （1）.     

Synthesis of CuCorePtShell Nanoparticles as Model Structures for Core–Shell Electrocatalysts by Direct Platinum Electrodeposition on Copper

The synthesis of Cu(core)Pt(shell) model catalysts by the direct electrochemical deposition of Pt on Cu particles is presented. Cu particles with an average diameter of 200 nm have been deposited on glassy‐carbon electrodes by double pulse electrodeposition from a copper sulfate solution. Subsequent deposition from a platinum nitrate solution under potential control allows for a high selectivity of the Pt deposition towards Cu. Using a combination of cyclic voltammetry, XPS and sputtering, the structure of the generated particles has been analyzed and their core–shell configuration proven. It is shown that the electrocatalytic activity for the oxygen reduction is similar to that of other PtCu catalyst systems. The synthesized structures could allow for the analysis of structure–activity relations of core–shell catalysts on the way to the simple and controlled synthesis of supported Cu(core)Pt(shell) nanoparticles as oxygen reduction catalysts.     

Asymmetric synthesis of (−)-tetrahydrolipstatin

Attempts toward the asymmetric synthesis of (−)-tetrahydrolipstatin are described. A palladium catalyzed Wacker-type reaction to convert an alkene to a ketone, highly diastereoselective reduction of a β-hydroxy ketone, selective oxidation of a diol, and modular synthesis are the key features of the successful approach.     

Transition Metal‐Free Reduction of Activated Alkenes Using a Living Microorganism

Microorganisms can be programmed to perform chemical synthesis via metabolic engineering. However, despite an increasing interest in the use of de novo metabolic pathways and designer whole‐cells for small molecule synthesis, the inherent synthetic capabilities of native microorganisms remain underexplored. Herein, we report the use of unmodified E. coli BL21(DE3) cells for the reduction of keto‐acrylic compounds and apply this whole‐cell biotransformation to the synthesis of aminolevulinic acid from a lignin‐derived feedstock. The reduction reaction is rapid, chemo‐, and enantioselective, occurs under mild conditions (37 °C, aqueous media), and requires no toxic transition metals or external reductants. This study demonstrates the remarkable promiscuity of central metabolism in bacterial cells and how these processes can be leveraged for synthetic chemistry without the need for genetic manipulation.     

3-Glycidoxypropyltrimethoxysilane mediated in situ synthesis of noble metal nanoparticles: application to hydrogen peroxide sensing

The in situ synthesis is reported of noble metal nanoparticles via 3-glycidoxypropyltrimethoxysilane mediated reduction of 3-aminopropyltrimethoxysilane treated metal salts during sol-gel processing. The method described involves the synthesis of uniform spherical nanoparticles of gold, silver and palladium with controlled size that can be directly utilized for thin film preparation. A detailed study of the synthesis and application of gold nanoparticles to the electrochemical detection of hydrogen peroxide was carried out and reveals that the amplification of hydrogen peroxide sensing is size-dependent. In addition, these nanoparticles exhibit excellent compatibility towards composite preparation. As an example, a nanocomposite with Prussian Blue (PB) is synthesized and found to be useful for the fabrication of chemically modified electrodes (CME). The resulting CME shows dramatic improvement in the electrochemistry of PB with gradual enhancement in electrocatalytic efficiency towards hydrogen peroxide sensing. The nanocomposite is used to study the direct and horseradish peroxidase (HRP)-catalyzed reduction of hydrogen peroxide. The results recorded for hydrogen peroxide analysis show an improvement in sensitivity and limit of detection on decreasing the size of gold nanoparticles in all cases.     

A new stereoselective synthesis of ciguatoxin right wing fragments

The right wings (13 and 14) of ciguatoxins were synthesized highly stereoselectively. Key transformations in the synthesis are (i) an oxiranyl anion strategy to attach the H ring, (ii) intramolecular carbonyl olefination to cyclize the J ring, (iii) regio- and stereoselective reduction of the epoxyacetal to install the C42-stereocenter, and (iv) stereoselective reductive etherification to construct the K ring. The present procedure greatly improved the stereoselectivity and efficiency in comparison to a previous synthesis. Remarkably, only 23 steps were required from monocyclic I ring 5 to construct the ciguatoxin right wings. The high practicality of the present synthesis ensures a sufficient supply of these complex fragments for total syntheses and biomedical applications.     

First total synthesis of phenylpyridine analogues of the antimitotic rhazinilam

The first synthesis of phenylpyridine analogues of rhazinilam and evaluation of these new structures as inhibitors of microtubule disassembly by interaction with tubulin are described. The synthesis is based on such key steps as picolinic metalation, hetero-ring cross-coupling and reduction of an acetyl group to an ethyl group. Elaboration of a quaternary picolinic carbon is one of the challenges of the synthesis. Biological evaluation of compounds bearing a quaternary picolinic carbon showed interactions with tubulin similar to (-)-rhazinilam but at a lower level.     

The Metal-Ammonia Reduction of 1-Naphthoic Acid

The reduction of aromatic compounds with alkali metals in liquid anhydrous ammonia (Birch Reduction and its modifications) has developed as an effective method for the synthesis of 1,4-cyclohexadiene derivatives, and has been the subject of several reviews.^1,2 In many cases, particularly with polynuclear compounds,² the reaction is complicated by subsequent isomerizations, and/or the reduction of initial products which are often themselves subject to reduction under the reaction conditions. Recently, we have shown that inverse quenching techniques can provide a substantial improvement in this reduction reaction by minimizing the effect of excess metal during the quenching process.³ Application of these methods to 1-naphthoic acid 1 have not only provided an excellent synthesis of 1,4-dihydro-1-naphthoic acid, but we believe will furnish a much improved general technique f o r the reduction of polynuclear aromatic carboxylic acids.     

A Simple Synthesis of an N‐Doped Carbon ORR Catalyst: Hierarchical Micro/Meso/Macro Porosity and Graphitic Shells

Replacing platinum as an oxygen reduction catalyst is an important scientific and technological challenge. Herein we report a simple synthesis of a complex carbon with very good oxygen reduction reaction (ORR) activity at pH 13. Pyrolysis of magnesium nitrilotriacetate yields a carbon with hierarchical micro/meso/macro porosity, resulting from in situ templating by spontaneously forming MgO nanoparticles and from etching by pyrolysis gases. The mesopores are lined with highly graphitic shells. The high ORR activity is attributed to a good balance between high specific surface area and mass transport through the hierarchical porosity, and to improved electronic conductivity through the graphitic shells. This novel carbon has a high surface area (1320 m²g^?1), and high nitrogen content for a single precursor synthesis (～6 %). Importantly, its synthesis is both cheap and easily scalable.     

In situ carbon nanotube synthesis by the reduction of NiO/γ-Al2O3 catalyst in methane

The synthesis of carbon nanotubes (CNTs) via chemical vapour deposition of methane on NiO/γ-Al2O3 catalyst has been investigated. The reduction behavior of NiO/γ-Al2O3 by methane was studied using thermogravimetric (TG) and X-ray diffraction (XRD) techniques. It was found that the NiO supported on γ-Al2O3, was reduced to Ni⁰ in methane atmosphere in the temperature range of 710--770 ℃. The catalytic activity of NiO/γ-Al2O3 for CNTs synthesis by in situ chemical vapour deposition of methane during the reduction was also investigated. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to observe the CNTs produced at various reduction temperatures. The results indicated that the reduction temperature exhibits obvious influence on the morphology and the yield of CNTs. CNTs with the diameter of about 20 nm were obtained at reduction temperature of 750 ℃, and higher reduction temperature (such as 800 and 850 ℃) led to an increase in CNTs diameter and a decrease in CNTs yield.