A new enantioselective α‐benzylation and α‐allylation of α‐tert‐butoxycarbonyllactones was devloped. α‐Benzylation and α‐allylation of α‐tert‐butoxycarbonylbutyrolactone and α‐tert‐butoxycarbonylvalerolactone under phase‐transfer catalytic conditions (50% cesium hydroxide, toluene, −60 °C) in the presence of (S,S)‐3,4,5‐trifluorophenyl‐NAS bromide (1 mol%) afforded the corresponding α‐substituted α‐tert‐butoxycarbonyllactones in very high chemical yields (up to 99%) and optical yields (up to 99% ee). The synthetic potential of this method has been successfully demonstrated by the asymmetric synthesis of unnatural α‐quaternary homoserines, 3‐alkyl‐3‐carboxypyrrolidine and 3‐alkyl‐3‐carboxypiperidine. 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
The effects of α‐, γ‐ and δ‐tocopherols on the stability and decomposition reactions of lipid hydroperoxides were studied. Isomerization and decomposition of cis,trans methyl linoleate hydroperoxides (cis,trans ML‐OOH) in hexadecane at 40 °C were followed by high‐performance liquid chromatography. Due to its higher hydrogen donating ability, α‐tocopherol was more efficient than γ‐ and δ‐tocopherols in inhibiting the isomerization of cis,trans ML‐OOH to trans,trans ML‐OOH. α‐Tocopherol stabilized hydroperoxides into the cis,trans configuration, whereas γ‐ and δ‐tocopherols allowed hydroperoxides to convert into trans,trans isomers. Thus, the biological importance of α‐tocopherol as compared to other tocopherols may be partly due to its better efficacy in protecting the cis,trans configuration of hydroperoxides formed, for example, in the enzymatic oxidation of polyunsaturated fatty acids. The isomeric configuration of hydroperoxides has an impact on biological activities of further oxidation products of polyunsaturated fatty acids. Paradoxically, the order of activity of tocopherols with regard to hydroperoxide decomposition was different from that obtained for hydroperoxide isomerization. γ‐ and δ‐tocopherols were more efficient inhibitors of ML‐OOH decomposition when compared to α‐tocopherol. A loss of antioxidant efficiency, observed as the tocopherol concentration increased from 2 to 20 mM, was highest for α‐tocopherol but was also evident for γ‐ and δ‐tocopherols. Thus, the differences in the relative effects of tocopherols at differing concentrations seem to result from a compromise between their radical scavenging efficiency and participation in side reactions of peroxidizing nature. 相似文献
The highly catalytic asymmetric α‐hydroxylation of 1‐tetralone‐derived β‐keto esters and β‐keto amides using tert‐butyl hydroperoxide (TBHP) as the oxidant was realized by a chiral N,N′‐dioxide‐magnesium ditriflate [Mg(OTf)2] complex. A series of corresponding chiral α‐hydroxy dicarbonyl compounds was obtained in excellent yields (up to 99%) with excellent enantioselectivities (up to 98% ee). The products were easily transformed into useful building blocks and the precursor of daunomycin was achieved in an asymmetric catalytic way for the first time. 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
The first highly enantioselective organocatalytic rearrangement of α‐acyloxy‐β‐keto sulfides to α‐acyloxy thioesters has been developed which provides a number of important synthetic building blocks in high yield and with excellent enantioselectivities (ee: up to 92%). 相似文献
The highly catalytic asymmetric α‐hydroxylation of β‐indanone esters and β‐indanone amides using peroxide as the oxidant was realized with a new C‐2′ substituted Cinchona alkaloid derivatives. The two enantiomers of α‐hydroxy‐β‐indanone esters could be obtained by simply changing the oxidant. This protocol allows a convenient access to the corresponding α‐hydroxy‐β‐indanone esters and α‐hydroxy‐β‐indanone amides with up to 99% yield and 98% ee.
An efficient catalytic asymmetric hydrogenation of racemic α‐arylcyclohexanones with an ethylene ketal group at the 5‐position of the cyclohexane ring via dynamic kinetic resolution has been developed, giving chiral α‐arylcyclohexanols with two contiguous stereocenters with up to 99% ee and >99:1 cis/trans‐selectivity. Using this highly efficient asymmetric hydrogenation reaction as a key step, (−)‐α‐lycorane was synthesized in 19.6% overall yield over 13 steps from commercially available starting material. 相似文献
A highly enantioselective Michael addition of cyclic 1,3‐dicarbonyl compounds to β,γ‐unsaturated α‐keto esters catalyzed by amino acid‐derived thiourea‐tertiary‐amine catalysts is presented. Using 5 mol% of a novel tyrosine‐derived thiourea catalyst, a series of chiral coumarin derivatives were obtained in excellent yields (up to 99%) and with up to 96% ee under very mild conditions within a short reaction time. 相似文献
α‐Conotoxin MII (α‐CTxMII) is a 16‐residue peptide with the sequence GCCSNPVCHLEHSNLC, containing Cys2–Cys8 and Cys3–Cys16 disulfide bonds. This peptide, isolated from the venom of the marine cone snail Conus magus, is a potent and selective antagonist of neuronal nicotinic acetylcholine receptors (nAChRs). To evaluate the impact of channel–ligand interactions on ligand‐binding affinity, homology models of the heteropentameric α3β2‐nAChR were constructed. The models were created in MODELLER with the aid of experimentally characterized structures of the Torpedo marmorata‐nAChR (Tm‐nAChR, PDB ID: 2BG9) and the Aplysia californica‐acetylcholine binding protein (Ac‐AChBP, PDB ID: 2BR8) as templates for the α3‐ and β2‐subunit isoforms derived from rat neuronal nAChR primary amino acid sequences. Molecular docking calculations were performed with AutoDock to evaluate interactions of the heteropentameric nAChR homology models with the ligands acetylcholine (ACh) and α‐CTxMII. The nAChR homology models described here bind ACh with binding energies commensurate with those of previously reported systems, and identify critical interactions that facilitate both ACh and α‐CTxMII ligand binding. The docking calculations revealed an increased binding affinity of the α3β2‐nAChR for α‐CTxMII with ACh bound to the receptor, and this was confirmed through two‐electrode voltage clamp experiments on oocytes from Xenopus laevis. These findings provide insights into the inhibition and mechanism of electrostatically driven antagonist properties of the α‐CTxMIIs on nAChRs. 相似文献
The first organocatalytic enantioselective Strecker synthesis of α‐quaternary α‐trifluoromethylated amino acids has been developed. Employing Takemoto’s thiourea catalyst the nucleophilic addition of trimethylsilyl cyanide to trifluoromethyl ketimines affords α‐amino nitriles in good to excellent yields (50–99%) and very good enantioselectivities (ee=83–95%). The enantiopure amino nitriles can be obtained by recrystallization. Deprotection and hydrolysis leads to the title amino acids. 相似文献
Highly regio‐ and diastereoselective 1,2‐addition of organolithium reagents to chiral fluoroalkyl α,β‐unsaturated N‐tert‐butanesulfinyl ketimines was developed, providing a general and efficient method for the asymmetric synthesis of structurally diverse α‐tertiary fluoroalkyl allylic amines in high yields and with excellent diastereoselectivities (dr up to>99:1). The synthetic application of the method was demonstrated by the rapid and convenient preparation of challenging α‐fluoroalkyl α‐amino acids with α‐tetrasubstituted carbon.
The direct α‐Csp2 H functionalization and thiomethylation of α‐oxoketene dithioacetals (DTAs) has been accomplished with dimethyl sulfoxide (DMSO) in the presence of iodine and a copper(I) salt for the first time. A prerequisite is the in situ iodination of the α‐Csp2 atom of dithioacetals that could offer other reaction channels. The operationally simple one‐pot protocol includes region‐defined consecutive iodination and sulfenylation of the challenging α‐Csp2 H bond of dithioacetals employing cheap and readily available reagents. DMSO here plays a dual role as thiomethyl source and solvent.
It was shown that the catalytic hydrogenation of α‐iminophosphonates by molecular hydrogen can serve as a convenient method for the synthesis of racemic and optically active α‐aminophosphonates. Up to 94% ee was achieved in the rhodium‐catalyzed enantioselective hydrogenation using chiral ligand (R)‐BINAP. 相似文献
A new enantioselective synthetic method for the synthesis of α,α‐dialkylmalonates with a quaternary carbon center was developed via α‐alkylation of prochiral malonates by phase‐transfer catalysis (PTC). Asymmetric α‐alkylation of benzylideneamino tert‐butyl α‐methylmalonates under phase‐transfer catalytic conditions in the presence of (S,S)‐3,4,5‐trifluorophenyl‐NAS bromide afforded the corresponding α,α‐dialkylmalonates in high yields (up to 97%) with excellent enantioselectivities (up to 98% ee). The products were then selectively hydrolyzed to chiral malonic monoacids under basic, acidic, or catalytic hydrogenation conditions.
The highly enantioselective cascade reaction between N‐protected α‐cyanoglycine esters and α,β‐unsaturated aldehydes is disclosed. The reaction represents a one‐step entry to polysubstituted 5‐hydroxyproline derivatives having a quaternary α‐stereocenter generally in high yields with up to >95:5 dr and 99:1 er. It is also a direct catalytic two‐step entry to functionalized α‐quaternary proline derivatives. 相似文献
A novel copper‐catalyzed oxidative alkylation of α‐amino carbonyl compounds with ethers has been established for the selective synthesis of α‐etherized α‐amino carbonyl compounds. This oxidative alkylation is achieved by dual C(sp3) H bond oxidative cross‐coupling, and its scope is expanded to α‐amino ketones, α‐amino esters and α‐amino amides.
An asymmetric Michael addition of α‐substituted cyano ketones to β,γ‐unsaturated α‐keto esters to form chiral dihydropyrans catalyzed by a series of α‐amino acid‐derived thiourea‐tertiary amines is presented. A novel tyrosine‐derived thiourea catalyst was identified as the optimal catalyst providing the desired product in 91–95% yields and with 90–96% ee at a low catalyst loading of 2.0 mol%. The utility of the reaction was exemplified by facile conversion of the dihydropyran product into pharmaceutically useful dihydropyridine. 相似文献