Synthesis of N-(methoxycarbonyl or isopropylcarbamoyl- methoxyphosphonyl)-α-amino acid ester and their stereomers

N-(methoxycarbonyl-methoxyphosphonyl)-α-amino add esters (I) were synthesized via the reaction of the corresponding phosphonyl chloride with amino acid ester hydrochlorides in the presence of a base. Compound I was aminated to yield N-(isopropylcarbainoyl-methoxyphosphonyl)-α-amino acid esters (II). With l-amino acids as starting materials, the isomers of products I and II were separated and their configurations were confirmed by the single crystal X-ray diffraction of II.     

Reliable folding of hybrid tetrapeptides into short β-hairpins

Five hybrid tetrapeptides, each consisting a central dipeptide segment of α-amino acid residues flanked by two aromatic γ-amino acid residues, are found to fold into well-defined β-hairpin conformations as shown by NMR, computational study, and X-ray structures. The turn loop of this β-hairpin motif accommodates different two-residue α-amino acid sequences from the highly flexible Gly-Gly, to the more restricted D-Pro-Gly. The presence of α-amino acid side chains enhances the stabilities of the ...     

Highly efficient synthesis of β-amino esters via Mannich-type reaction under solvent-free conditions using ZnCl_2 catalyst

β-Amino esters were synthesized via ZnCl_2-catalyzed Mannich-type reaction of imines and malonate esters under solvent-free conditions in 6 min.Theβ-amino ester was converted into the corresponding aspartic acid derivatives.     

Synthesis of Novel C2-Symmetrical Bidentate Phosphoramidite Ligands for Rh-catalyzed Asymmetric Hydrogenation of β-（Acylamino）acrylates

Enantiomerically pure β-amino acids and their derivatives are especially attractive due to their vital importance for biochemical and medicinal applications1. One of the most convenient paths to β-amino acids involves the asymmetric hydrogenation of the…     

Concise synthesis of valuable chiral N-Boc-β-benzyl-β-amino acid via construction of chiral N-Boc-3-benzyl-5-oxoisoxazolidine through cross-metathesis/conjugate addition/oxidation

Valuable chiral N-Boc-β-benzyl-β-amino acid was concisely synthesized via construction of chiral NBoc-3-benzyl-5-oxoisoxazolidine through cross-metathesis/conjugate addition/oxidation.All of the starting materials for the synthesis of chiral N-Boc-β-benzyl-β-amino acid are cheap,and two-step short procedure make it easy for the rapid construction of various chiral β-arylmethyl-β-amino acids and important drugs,such as sitagliptin phosphate.     

Oxalic acid catalyzed solvent-free one pot synthesis of coumarins

Oxalic acid was found to be an efficient catalyst for Pechmann condensation,which includes the reaction between phenols andβ-keto esters leading to formation of coumarin derivatives.The advantages of present methods are the use of cheap and easy available catalyst,solvent-free reaction conditions,better yields and shorter reaction time.     

α-氨基酸与氯化铷在水溶液中焓相互作用参数

The mixing enthalpies of aqueous heavy rare alkali metal chloride RbC1 solutions with aqueous α-amino acid (Loglycine, L-alanine and α-aminobutyric acid) solutions, as well as the dilution enthalpies of RbC1 and α-amino acid solutions in pure water had been measured at 298.15K. The transfer enthalpies of RbCI from pure water to aqueous α-amino acid solutions could be obtained from these data. The enthalpic pair interaction parameters of RbC1 with α-amino acid in water have been evaluated according to the McMillan-Mayer theory and discussed in terms of the electrostatic interaction, structure interaction and Savage-wood group additivity mode.     

An Efficient One-pot Synthesis of β-Amino/β-Acetamido Carbonyl Compounds via ZrCl4-catalyzed Mannich-type Reaction

Zirconium(IV) chloride catalyzed efficient one-pot synthesis of β-amino/β-acetamido carbonyl compounds at room temperature is described. In the presence of ZrCl4, the three-component Mannich-type reaction via a variety of in situ generated aldimines, with various ketones, aromatic aldehydes and aromatic amines in ethanol, led to the formation of β-amino carbonyl compounds and the four-component Mannich-type reaction of aromatic aldehydes with various ketones, acetonitrile and acetyl chloride resulted in the corresponding β-acetamido carbonyl compounds in high to excellent yields. This methodology has also been applied towards the synthesis of dimeric β-amino/β-acetamido carbonyl compounds.     

Efficient Lewis Acids Catalyzed Aza-Michael Reactions of Enones with Carbamates

The β-amino carbonyl functionality is not only a segment of biologically important natural products but also a versatile intermediate for the synthesis of nitrogen-containing compounds.1 The development of novel synthetic methods leading to β-amino ketone, β-amino acids or their derivatives has attracted much attention in organic synthesis.2 Among the traditional methods for generating β-amino carbonyl compounds, Mannich-type reaction is one of the classical and powerful methods.3 However,…     

One-pot Approach to the Conversion of Alcohols into α-Halo-α,β-unsaturated Esters

α-Halo-α, β-unsaturated esters are important intermediates in organic synthesis. For example, they are used for α-amino acid preparation1 and vinylogous Darzen reactions2, as a versatile fluorinated building block, they are also used for the preparati…     

Diastereoselective α—Alkylation of β—Amino Esters：Preparation of Novel α—Substituted β—Amino Esers from α—Amino Acids

Enantiomerically pure α-substituted β-amino esters were prepared from natural L-α-amino acids through Arndt-Eistert homologation and diastereoselective α-alkylation.     

Silicon-mediated enantioselective synthesis of structurally diverseα-amino acid derivatives

The catalytic asymmetric synthesis of novel and chiral amino acid derivatives with unconventional chemo-, diastereo-, and enantio-selectivity remains a paramount challenge. Herein we reported a novel protocol for the use of highly enantioselective copper-catalyzed cycloaddition of α,β-unsaturated acylsilanes as a springboard reaction for the facile synthesis of structurally diversified pyrrolidines and complicated α-amino esters by desilylation. The newly developed process could provide a wide range of synthetically useful acylsilane-substituted pyrrolidines(ASiP) in high yields and excellent diastereo-and enantioselectivities with Cu/(R)-XylBINAP complex as the catalyst. And the downstream desilylation transformation enables to expand the potntial applications of 1,3-dipolar cycloaddition in the construction of structurally unique amino acid derivatives, in which an unprecedented and concerted fluoride anion-promoted C–X(X=H, Si, N, C) bond cleavage occurred to the enantioselective construction of aldehyde-substituted pyrrolidines, linear cinnamaldehyde or alkene-substituted amino esters in high ee values.     

The structural analysis of the inclusion complex of β-cyclodextrin with m-nitrophenoxyacetic acid

The inclusion complex of β-cyclodextrin with m-nitrophenoxyacetic acid was studied by single crystal X-ray diffraction,2D NMR spectroscopy and semi-empirical methods AMI.The crystallographic study shows that two β-cyclodextrins are held together by hydrogen bonds to form head-to-head dimers.The disordered guest molecule adjusts itself to attain the most stable accommodation into the cavity in which the nitro group is located at the dimer interface while the carboxyl group is buried in the primary hydroxyl groups of β-cyclodextrin.The guest inside the cavity is disordered over two sites and exhibits mobility.Moreover,2D NMR spectroscopy and theoretical study show the same inclusion behavior.In comparison to the inclusion complex of β-cyclodextrin with p-nitrophenoxyacetic acid,the host-guest stoichiometries are different,i.e.,2:1 for m-nitrophenoxyacetic acid and 1:1 for p-nitrophenoxyacetic acid,while the inclusion orientation and the packing pattern of the host are similar in both complexes.     

Catalytic enantioselective synthesis of β-amino alcohols by nitrene insertion

Chiral β-amino alcohols are important building blocks for the synthesis of drugs, natural products, chiral auxiliaries, chiral ligands and chiral organocatalysts. The catalytic asymmetric β-amination of alcohols offers a direct strategy to access this class of molecules. Herein, we report a general intramolecular C(sp³)–H nitrene insertion method for the synthesis of chiral oxazolidin-2-ones as precursors of chiral β-amino alcohols. Specifically, the ring-closing C(sp³)–H amination of N-benzoyloxycarbamates with 2 mol% of a chiral ruthenium catalyst provides cyclic carbamates in up to 99% yield and with up to 99% ee.The method is applicable to benzylic, allylic, and propargylic C–H bonds and can even be applied to completely non-activated C(sp³)–H bonds, although with somewhat reduced yields and stereoselectivities. The obtained cyclic carbamates can subsequently be hydrolyzed to obtain chiral β-amino alcohols. The method is very practical as the catalyst can be easily synthesized on a gram scale and can be recycled after the reaction for further use. The synthetic value of the new method is demonstrated with the asymmetric synthesis of a chiral oxazolidin-2-one as intermediate for the synthesis of the natural product aurantioclavine and chiral β-amino alcohols that are intermediates for the synthesis of chiral amino acids, indane-derived chiral Box-ligands, and the natural products dihydrohamacanthin A and dragmacidin A.     

潜在的大环锌金属蛋白酶抑制剂的设计与合成

A series of succinate-derived macrocyclic amides 1 were synthezized using ring-closing metathesis in the keystep.The substrate scope includes tings of 11 to 14 members.The cyclic dicarboxylic acids 1 represent a family ofnew model compounds for potential zinc metalloprotease inhibitors.The metathesis precursors were provided byamide coupling of tert-butyl 3-earboxyhex-5-enoate 2 with numerous side chain alkenylated amino acid esters ofgeneral type 3 derived from L-tyrosine and L-cysteine.     

Soluble Polymer-Supported Synthesis of α-Amino Acid Derivatives

Due to the central role played by α-amino acid in chemistry and biology, the development of versatile and new methodology for the synthesis of natural and unnatural α-amino acid has emerged as an important and challenging synthetic endeavour for organic chemists.[1] Among the various methodologies reported for α-amino acid synthesis, [2,3] the solid-phase organic synthesis (SPOS) has served as an important approach. [4] However, inherent prob lems on solid supports are reactive site accessibility, site-site interaction and monitoring of the reaction.     

Effect of the Esters of Gallic Acid on Model and Human Blood Platelet Membranes Studied by Fourier Transform Infrared Spectroscopy

Gallic acid is one of the components of Chinese herbal drug Radix paeoniae used for promoting blood circulation to remove blood stasis. This paper studied the effects of gallic acid and its esters (e.g. ethyl, propyl, isobutyl and butyl gallate) on model and human blood platelet membranes by FTIR which was used for monitoring the physical state of the acyl chain, interfacial and head group region of the membrane lipid bilayer. From the experimental results it can be seen that the gallic acid and its esters have the modifying function on the pure and cholesterol-containing DPPC model membranes, and have the quantity-effective and structural-effective relationships. In addition, it is discovered that these esters have the modifying effect on the structure of human blood platelet membrane and can reverse the effect of ADP. That the effect of the esters of gallic acid counteracts the effect of cholesterol and ADP on human blood platelet perhaps provides a new explanation of the mechanism of Chinese herbal d     

Stereoselectivities in α- and β-Amino Acids Catalyzed Mannich Reactions Involving Cyclohexanone

The effects of two different amino acid catalysts on the stereoselectivities in the direct Mannich reactions of cyclohexanone,p-anisidine and p-nitrobenzaldehyde were studied with the aid of density functional theory.Transition states of the stereo-determining C C bond-forming step with the addition of enamine intermediate to the imine for the L-proline(·-amino acid) and (R)-3-pyrrolidinecarboxylic acid(·-amino acid)-catalyzed processes were reported.B3LYP/6-31G calculations provide a good explanation for t...     

Enantioselective trapping of oxonium ylide intermediates by N-benzhydryl-α-imino ester:Synthesis of β-tetrasubstituted α-amino acids

A synergistic rhodium(Ⅱ)/phosphoric acid catalyzed three component reaction of 3-diazooxindoles,alcohols and N-benzhydryl-α-imino ester is developed for the efficient construction of chiral β-alkoxy C~β-tetrasubstituted α-amino acid derivatives in good yields and with excellent diastereoselectivities and high enantioselectivities.The synthetic application of the resulting products was illustrated by reducing with Pd/C under H_2 atmosphere followed reacting with CSCl_2 at room temperature to rapid afford 3-spirocyclic oxindole in a good yield with a chirality retainment.The three-component reaction is proposed to proceed through an electrophilic trapping of the oxonium ylides by N-benzhydryl-α-imino ester.     

Asymmetric reduction of representative ketones with a bis-chiral oxazaborolidine system

In recent years, many optically active β-amino alcohols, mostly derived from naturally occurring α-amino acids, have been incorporated into the asymmetric synthesis as chiral auxiliaries or ligands.1 An effective asymmetric catalysts, the oxazaborolidine-borane reagents, which were originally pioneered by Itsuno and Corey,2 were generally prepared from chiral β-amino alcohols by the reaction with boric acid or formed in situ in the presence of borane. These reagents provide excellent enanti…