An intramolecular imination/azidation sequence has been realized through the tetrakis(acetonitrile)copper(I) hexafluorophophate [Cu(CH3CN)4PF6]‐catalyzed reaction of γ,δ‐unsaturated ketone O‐benzoyl oximes with trimethylsilyl azide (TMSN3). The reaction proceeds via the copper‐mediated N O cleavage and subsequent C N forming 5‐exo cyclization. The thus formed intermediate is then azidated to afford the corresponding dihydropyrrole product. Preliminary mechanistic investigations suggest that the cyclization step does not involve a radical intermediate.
A method for the preparation of 11α‐hydroxy derivatives of lithocholic and chenodeoxycholic acids, recently discovered to be natural bile acids, is described. The principal reactions involved were (1) elimination of the 12α‐mesyloxy group of the methyl esters of 3α‐acetate‐12α‐mesylate and 3α,7α‐diacetate‐12α‐mesylate derivatives of deoxycholic acid and cholic acid with potassium acetate/hexamethylphosphoramide; (2) simultaneous reduction/hydrolysis of the resulting △11‐3α‐acetoxy and △11‐3α,7α‐diacetoxy methyl esters with lithium aluminum hydride; (3) stereoselective 11α‐hydroxylation of the △11‐3α,24‐diol and △11‐3α,7α,24‐triol intermediates with B2H6/tetrahydrofuran (THF); and (4) selective oxidation at C‐24 of the resulting 3α,11α,24‐triol and 3α,7α,11α,24‐tetrol to the corresponding C‐24 carboxylic acids with NaClO2 catalyzed by 2,2,6,6‐tetramethylpiperidine 1‐oxyl free radical (TEMPO) and NaClO. In summary, 3α,11α‐dihydroxy‐5β‐cholan‐24‐oic acid and 3α,7α,11α‐trihydroxy‐5β‐cholan‐24‐oic acid have been synthesized and their nuclear magnetic resonance (NMR) spectra characterized. These compounds are now available as reference standards to be used in biliary bile acid analysis. 相似文献
Nicotinic acetylcholine receptors (nAChRs) play an important role in many central nervous system disorders such as Alzheimer’s and Parkinson’s diseases, schizophrenia, and mood disorders. The α4β2 subtype has emerged as an important target for the early diagnosis and amelioration of Alzheimer’s disease symptoms. Herein we report a new class of α4β2 receptor ligands characterized by a basic pyrrolidine nucleus, the basicity of which was properly decreased through the insertion of a fluorine atom at the 3‐position, and a pyridine ring carrying at the 3‐position substituents known to positively affect affinity and selectivity toward the α4β2 subtype. Derivatives 3‐(((2S,4R)‐4‐fluoropyrrolidin‐2‐yl)methoxy)‐5‐(phenylethynyl)pyridine ( 11 ) and 3‐((4‐fluorophenyl)ethynyl)‐5‐(((2S,4R)‐4‐fluoropyrrolidin‐2‐yl)methoxy)pyridine ( 12 ) were found to be the most promising ligands identified in this study, showing good affinity and selectivity for the α4β2 subtype and physicochemical properties predictive of a relevant central nervous system penetration. 相似文献
A new enantioselective α‐alkylation of α‐tert‐butoxycarbonyllactams for the construction of β‐quaternary chiral pyrrolidine and piperidine core systems is reported. α‐Alkylations of N‐methyl‐α‐tert‐butoxycarbonylbutyrolactam and N‐diphenylmethyl‐α‐tert‐butoxycarbonylvalerolactam under phase‐transfer catalytic conditions (solid potassium hydroxide, toluene, −40 °C) in the presence of (S,S)‐3,4,5‐trifluorophenyl‐3,3′,5,5′‐tetrahydro‐2,6‐bis(3,4,5‐trifluorophenyl)‐4,4′‐spirobi[4H‐dinaphth[2,1‐c:1′,2′‐e]azepinium] bromide [(S,S)‐NAS Br] (5 mol%) afforded the corresponding α‐alkyl‐α‐tert‐butoxycarbonyllactams in very high chemical (up to 99%) and optical yields (up to 98% ee). Our new catalytic systems provide attractive synthetic methods for pyrrolidine‐ and piperidine‐based alkaloids and chiral intermediates with β‐quaternary carbon centers. 相似文献
An efficient strategy for a high‐yielding and stereoselective synthesis of α‐trifluoromethyl unsaturated carboxylic acids directly from the reactions of 3,3,3‐trifluoropropanoic acid (CF3CH2COOH) with various aryl aldehydes in the presence of titanium tetrachloride (TiCl4) is reported here for the first time, which is a valuable expansion for the classical Knoevenagel reaction. Because these compounds may have potential applications in organic electronics and can be easily converted to the corresponding fluorinated alcohols and amino acids with excellent bioactivity, this route should be a good choice for the preparation of α‐trifluoromethyl‐containing derivatives. 相似文献
An efficient and generally applicable protocol for decarboxylative coupling of α,α‐difluoroarylacetic acids with ethynylbenziodoxolone (EBX) reagents has been developed, affording α,α‐difluoromethylated alkynes bearing various functional groups in moderate to excellent yields. Remarkably, this potassium persulfate (K2S2O8)‐promoted reaction employs water as solvent under transition metal‐free conditions, thus providing a green synthetic approach to α,α‐difluoromethylated alkynes.
α‐Substituted β‐acetyl amides could undergo C C bond cleavage to form α‐keto amides when treated with copper(II) chloride (CuCl2) and boron trifluoride diethyl etherate (BF3⋅OEt2) under an oxygen atmosphere. The yield can be increased by the addition of tert‐butyl hydroperoxide which alone can also effect the reaction. The reaction provides a new protocol for the synthesis of α‐keto amides.
This work reports the use of acrylated fatty acid methyl ester (AFAME) as a biomonomer for the synthesis of bio‐based hybrid magnetic particles poly(styrene‐co‐AFAME)/γ‐Fe2O3 produced by miniemulsion polymerization. Poly(styrene‐co‐AFAME)/γ‐Fe2O3 can be tailored for use in various fields by varying the content of AFAME. The strategy employed is to encapsulate superparamagnetic iron oxide nanoparticles (SPIONs) as γ‐Fe2O3 into a styrene/AFAME‐based copolymer matrix. Raman spectroscopy is employed to ensure the formation of the SPIONs (γ‐Fe2O3) obtained by a co‐precipitation technique followed by oxidation of Fe3O4. The functionalization of SPIONs with oleic acid (OA) is carried out to increase the SPIONs–monomer affinity. The presence of OA on the surface of γ‐Fe2O3 is certified by identification of main absorption bands by fourier‐transform infrared spectroscopy (FTIR). Thermal analysis (differential thermogravimetry/differential thermo analysis and differential scanning calorimetry) results of poly(styrene‐co‐AFAME)/γ‐Fe2O3 show an increase in AFAME content leading to a lower copolymer glass transition temperature (Tg). Dynamic light scattering (DLS) measurements result in poly(styrene‐co‐AFAME)/γ‐Fe2O3 particles with diameter in the range of 100–150 nm. It is also observed by transmission electron microscopy (TEM) and cryo‐TEM techniques that γ‐Fe2O3 particles are successfully encapsulated into the poly(styrene‐co‐AFAME) matrix. 相似文献
A detailed structural analysis on the in situ synthesized β‐Ca3(PO4)2/α‐Fe2O3 composites is demonstrated. Compositional ratios, the influence and occupancy of iron at the β‐Ca3(PO4)2 lattice, oxidation state of iron in the composites are derived from analytical techniques involving XRD, FT‐IR, Raman, refinement of the powder X‐ray diffraction and X‐ray photoelectron spectroscopy. Iron exists in the Fe3+ state throughout the investigated systems and favors its occupancy at the Ca2+(5) site of β‐Ca3(PO4)2 until critical limit, and thereafter crystallizes as α‐Fe2O3 at ambient conditions. Fe3+ occupancy at the β‐Ca3(PO4)2 lattice yields a Ca9Fe(PO4)7 structure that is isostructural with its counterpart. A strong rise in the soft ferromagnetic behavior of β‐Ca3(PO4)2/α‐Fe2O3 composites is obvious that depends on the content of α‐Fe2O3 in the composites. Overall, the diverse level of iron inclusions at the calcium phosphate system with a Ca/P ratio of 1.5 yields a structurally stable β‐Ca3(PO4)2/α‐Fe2O3 composites with assorted compositional ratios. 相似文献
A novel enzymatic production system of optically pure β‐hydroxy α‐amino acids was developed. Two enzymes were used for the system: an N‐succinyl L ‐amino acid β‐hydroxylase (SadA) belonging to the iron(II)/α‐ketoglutarate‐dependent dioxygenase superfamily and an N‐succinyl L ‐amino acid desuccinylase (LasA). The genes encoding the two enzymes are part of a gene set responsible for the biosynthesis of peptidyl compounds found in the Burkholderia ambifaria AMMD genome. SadA stereoselectively hydroxylated several N‐succinyl aliphatic L ‐amino acids and produced N‐succinyl β‐hydroxy L ‐amino acids, such as N‐succinyl‐L ‐β‐hydroxyvaline, N‐succinyl‐L ‐threonine, (2S,3R)‐N‐succinyl‐L ‐β‐hydroxyisoleucine, and N‐succinyl‐L ‐threo‐β‐hydroxyleucine. LasA catalyzed the desuccinylation of various N‐succinyl‐L ‐amino acids. Surprisingly, LasA is the first amide bond‐forming enzyme belonging to the amidohydrolase superfamily, and has succinylation activity towards the amino group of L ‐leucine. By combining SadA and LasA in a preparative scale production using N‐succinyl‐L ‐leucine as substrate, 2.3 mmol of L ‐threo‐β‐hydroxyleucine were successfully produced with 93% conversion and over 99% of diastereomeric excess. Consequently, the new production system described in this study has advantages in optical purity and reaction efficiency for application in the mass production of several β‐hydroxy α‐amino acids.
Chiral bioinspired iron complexes of N4 ligands based on the ethylenediamine backbone display remarkable levels of enantioselectivity for the first time in the asymmetric epoxidation of α,β‐unsaturated ketones using hydrogen peroxide (up to 87% ee) or peracetic acid as oxidant, respectively. Notablely, isotopic labeling with H218O strongly demonstrated that there is a reversible water binding step prior to generation of the significant intermediate. Besides, the complex [L2Fe(III)2(μ‐O)(μ‐CH3CO2)]3+ usually derived from the decay of the LFe(IV)O species or thermodynamic sinks for a number of iron complexes was identified by HR‐MS. In addition, the possible mechanisms were proposed and LFe(V)O species may be the main active intermediate in the catalytic system. 相似文献
(2S,3aR,7aS)‐Perhydroindolic acid, the key intermediate in the synthesis of trandolapril, and its trans‐isomers, were readily prepared. These proline‐like molecules are unique in that they contain a rigid bicyclic structure, with two hydrogen atoms trans to each other at the bridgehead carbon atoms. These molecules were used successfully as chiral organocatalysts in asymmetric domino Michael addition/cyclization reactions of aldehyde esters with β,γ‐unsaturated α‐keto esters. They proved to have excellent catalytic behavior, allowing for the synthesis of multi‐substituted, enantiomerically enriched hemiacetal esters. Under optimal conditions (using 10 mol% catalyst loading), a series of β,γ‐unsaturated α‐keto esters was examined with up to 99% de, ee and yield, respectively. Additionally, the enantiomerically enriched hemiacetal esters could be readily transformed into their corresponding bioactive pyrano[2,3‐b]pyrans (possessing a multi‐substituted bicyclic backbone). 相似文献
Efficient one‐step syntheses of α,β‐ and β,β‐dihaloenones were achieved by ruthenium(II)‐catalyzed reactions between cyclic or acyclic diazodicarbonyl compounds and oxalyl chloride or oxalyl bromide in moderate to good yields. This methodology offers several significant advantages, which include ease of handling, mild reaction conditions, one‐step reaction, and the use of an effective and non‐toxic catalyst. The synthesized compounds were further transformed into highly functionalized novel molecules bearing aromatic rings on the enone moiety using the Suzuki reaction.