Solid-state linear-dichroic infrared (IR-LD) spectroscopic and theoretical characterization of 2-[(2-ethoxy-3,4-dioxocyclobut-1-en-yl)amino]propanamide

2-[(2-Ethoxy-3,4-dioxocyclobut-1-en-yl)amino]propanamide (N-alaninamidoamide of squaric acid ethyl ester) has been characterized structurally and spectroscopically by ab initio calculations and IR-LD spectroscopy of oriented crystals suspended in a nematic liquid crystal. The results are compared with single crystal X-ray structures illustrating the possibilities of this experimental approach to obtaining structural information as well as assigning IR bands.     

Measurements of the solubilities of derivatized amino acids in supercritical carbon dioxide

The solubilities of phenylalanine and tyrosine in supercritical carbon dioxide (SCCO₂) were measured after derivatization as the N-acetyl amino acid ethyl ester, N-carbobenzoxy amino acid and N-acetyl amino acid. Using an SCCO₂ flow system, a measuring method of the saturated solubilities of the derivatized amino acids was established in which the contact height of the extraction cell, i.e. a packed column, is increased till the concentration of a derivatized amino acid at the exit of the cell reaches a plateau. The solubilities of N-acetyl phenylalanine ethyl ester (APEE) exceeded 0.001 mole fraction, which is higher than those of caffeine produced in industrial SCCO₂ processes. A possible way of separating the amino acid mixtures using polarity differences in different amino acid side chains was demonstrated using the solubility data of the N-acetyl-amino acid ethyl esters in SCCO₂, as the solubilities of APEE are higher than those of N-acetyl tyrosine ethyl ester by two orders of magnitude.     

Development of N,N-bis(perfluoroalkanesulfonyl)squaramides as new strong Brønsted acids and their application to organic reactions

New strong Brønsted acids derived from a squaric acid scaffold bearing different perfluoroalkanesulfonyl groups have been developed and applied to several organic reactions. These squaramides are bench-stable and exhibit much higher reactivities in several organic reactions than squaric acid itself. N,N-Bis(trifluoromethanesulfonyl)squaramide 2a was applied to the Mukaiyama aldol reaction and Mukaiyama Michael reaction. Mechanistic studies revealed that the Brønsted acid might be the predominant catalyst through direct protonation of carbonyl compound by the acid itself rather than the silylated Brønsted acid. The utility of this acid 2a was further extended to Hosomi-Sakurai allylation of aldehydes and a carbonyl-ene reaction. Furthermore, other squaramides 2b and c bearing longer perfluoroalkyl chains have been developed, which are also bench-stable and displayed similar reactivities with squaramide 2a in several organic reactions.     

Spectroscopic and structural studies of some oxocarbon condensation products: IV. a spectroscopic and mass spectral investigation of some derivatives of squaric acid

Proton-NMR, vibrational and mass spectral data are reported for nine molecules derived from. squaric acid. The data substantiate the cyclobuta[b]quinoxaline structure for six of the molecules whereas the others are shown to be simple derivatives of squaric acid.     

Synthesis and chiroptical properties of amino acid-derived poly(methylpropargyl ester)s

Chiral methylpropargyl ester monomers containing amino acid moieties, N-(tert-butoxycarbonyl)-l-alanine (R)-1-methylpropargyl ester (1), N-(benzyloxycarbonyl)-l-valine (R)-1-methylpropargyl ester (2), and N-(tert-butoxycarbonyl)-l-O-cyclohexyl-l-glutamic acid (R)-1-methylpropargyl ester (3) were synthesized and polymerized with (nbd)Rh⁺[η⁶-C₆H₅B⁻(C₆H₅)₃] to give the corresponding polymers with number-average molecular weights ranging from 32 700 to 64 100 in 84-85% yields. The polymers were soluble in toluene, CHCl₃, CH₂Cl₂, THF, DMF, and DMSO, but insoluble in hexane, diethyl ether, and MeOH. The specific rotation and circular dichroism (CD) spectroscopic studies revealed that poly(1)-poly(3) took predominantly one-handed helical structures in the solvents, wherein the degree of one-handedness and tightness of the helix depended on the solvent. The helical structure of the polymers was stable to the addition of MeOH and heat.     

An efficient chiral synthesis of fluoro-containing amino acids: N-benzyloxycarbonyl-2-amino-4,4-difluorobutyric acid methyl ester and its analogs

Fluoro-containing amino acids, N-benzyloxycarbonyl-2-amino-4,4-difluorobutyric acid methyl ester and analogs, were prepared in high enantiomeric excess. Incorporation of 2-amino-4,4-difluoro butyric acid as P1 group provided a potent HCV NS3 protease inhibitor.     

Synthesis and application in SPPS of a stable amino acid isostere of palmitoyl cysteine

(S)-2-Amino-4-(2-pentadecyl-1,3-dioxolan-2-yl)-butanoic acid, 11, Pdiob, a synthetic analogue C-isostere of palmitoylated cysteine, has been prepared starting from tetrabenzyl glutamic acid. The less hindered benzyl carboxylate ester was transformed into the corresponding β-ketophosphonate and subjected to a Horner-Wadsworth-Emmons reaction followed by hydrogenation/hydrogenolysis. This product was used for the preparation on solid phase and under microwave dielectric heating of a highly lipidated peptide that can be considered as an acid stable analogue of the C-terminus of the H-Ras heptapeptides 180-186.     

Diastereoselective total synthesis of (+)-morusimic acid B, an amino acid from Morus alba

An efficient, flexible and diastereoselective synthesis of the naturally occurring pyrrolidine amino acid, (+)-morusimic acid B, has been accomplished. Starting from chiral, optically active (+)-(3S)-hydroxy butyric acid methyl ester the key steps of our synthesis are diastereoselective α-alkylation of its dianion to introduce the main part of the side chain, Curtius rearrangement of the hydrazide derivative to a 2-oxazolidinone followed by N→π-cyclization with mercury(II) acetate to generate the cis-2,5-disubstituted pyrrolidine ring. The remote C-3 stereocentre is established after chain elongation with the dianion of methyl acetoacetate and asymmetric hydrogenation of the resulting β-oxoester with Noyori's Ru(II)-(R)-BINAP catalyst.     

N-方酰麻黄碱配体的合成及催化前手性芳酮的不对称还原反应

方酸与醇反应成方酸二酯,后者与天然麻黄碱反应得到N-方酰麻黄碱或N-方酰双麻黄碱。单N-方酰麻黄碱与脂肪胺及硫氢化钠等反应合成了C-3位含氮和含硫的系列配体。首次将这些方酰麻黄碱配体经原位制备手性恶唑硼烷催化前手性芳酮及二酮的不对称还原反应,得到化学产率和e.e.值分别为85%-98%和52.5%-87.4%的手性仲醇。新化合物的结构已IR,^1H NMR,MS和元素分析所证实,化合物4b的晶体结构用X射线射确认。     

Antifungal activities of amino acid ester functional pyrazolyl compounds against Fusarium oxysporum f.sp. albedinis and Saccharomyces cerevisiae yeast

Series of functional multidendate ligands based on pyrazole and amino acid derivatives were prepared in good and excellent yields (75–5%) by condensation of one equivalent of amino acid ester hydrochloride substrates with two equivalents of (3,5-dimethyl-1H–pyrazol-1-yl)methanol. These tridentate functionalized compounds and their starting materials were screened for their antifungal activities against Fusarium oxysporum f.sp. albedinis and the yeast of Saccharomyces cerevisiae. Considerable activities were recorded with respect to the two studied microorganisms.     

Synthetic applications of di-tert-butoxyethyne,II: New syntheses of squaric,semisquaric and croconic acids

New synthetic entries to: a) the semisquaric acid skeleton of the natural mycotoxin “moniliformin”; b) the squaric acid system, and c) the croconic acid system, via (η-tetra-tert-butoxycyclopentadienone)(η-cyclopentadienyl)cobalt, starting from di-tertbutoxyethyne are reported.     

Resolution of non-protein amino acids via the microbial protease-catalyzed enantioselective hydrolysis of their N-unprotected esters

In the Aspergillus oryzae protease-catalyzed ester hydrolysis, substitution of N-unprotected amino acid esters for the corresponding N-protected amino acid esters resulted in a large enhancement of the hydrolysis rate, while the enantioselectivity was deteriorated strikingly when the substrates employed were the conventional methyl esters. This difficulty was overcome by employing esters bearing a longer alkyl chain such as the isobutyl ester. Utilizing this ester, amino acids carrying an aromatic side chain were resolved with excellent enantioselectivities (E=50 to >200). With amino acids bearing an aliphatic side chain also, good results in terms of the hydrolysis rate and enantioselectivity were obtained by employing such an ester as the isobutyl ester. Moreover, the enantioselectivity proved to be enhanced further by conducting the reaction at low temperature. This procedure was applicable to the case where the enantioselectivity was not high enough even by the use of the isobutyl ester.     

Discovery of carboxypeptidase Y as a catalyst for the incorporation of sterically demanding α-fluoroalkyl amino acids into peptides

The first example of a direct enzymatic coupling of two different, sterically demanding C^α-fluoroalkyl amino acids to amino acid nucleophiles is reported. N-Protected Ala methyl ester derivatives bearing a methyl-, difluoromethyl-, or trifluoromethyl group, respectively, instead of the α-proton were accepted as substrates by carboxypeptidase Y and could, therefore, be coupled directly to various nucleophiles.     

Tetramethylcyclobutadiene)cobalt complexes of protected aromatic amino acids*

Reactions of [(C4Me4)Co(MeCN)3]PF6 with aromatic amino acid derivatives give the arene complexes [(C4Me4)Co(amino acid)]PF6 (amino acid = ethyl ester of N-acetylphenylalanine, N-acetyltyrosine or N-acetyltryptophan) in 75–85% yields; the structure of the tyrosine complex was determined by X-ray diffraction.     

New C2-symmetric 2,2′-bipyridine crown macrocycles for enantioselective recognition of amino acid derivatives

A series of new C₂-symmetric 2,2′-bipyridine-contaning crown macrocycles 1-4 has been developed for enantiomeric recognition of amino acid derivatives. These new macrocycles have been showed to be strong complexing agents for primary organic ammonium salts (with K up to 4.83×10⁵ M⁻¹ and −ΔG₀ up to 32.4 kJ mol⁻¹) and also useful chromophores for UV-vis titration studies. These macrocyclic hosts exhibited enantioselective binding towards the (S)-enantiomer of phenylglycine methyl ester hydrochloride (Am1) with K_(S)/K_(R) up to 2.10 (ΔΔG₀=−1.84 kJ mol⁻¹) in CH₂Cl₂ with 0.25% CH₃OH. The structure-binding relationship studies showed that the aromatic subunit and the ester group of the ammonium guests are both important for good enantioselectivity. In addition, the host-guest complexes have been studied using various NMR experiments.     

Synthesis of a C3-symmetric macrocycle with alternating sugar amino acid and tyrosine residues

A C₃-symmetric macrocycle with alternating sugar amino acid and tyrosine residues was synthesized in seven steps from tyrosine tert-butyl ester and a sugar amino acid precursor derived from D-glucosamine. An Fmoc-protected D-glucosamine derivative was oxidized at C-6 to give the sugar amino acid, which was immediately coupled to tyrosine tert-butyl ester to produce an orthogonally protected building block. This building block was subsequently elongated to the trimer via the dimer, and finally cyclized to give the C₃-symmetric macrocycle.     

Spectroscopic and structural study of novel 8-aminoquinoline derivative embedded in nematic host

We have reported a novel derivative of 8-aminoquinoline, which represents ester-amide of squaric acid ethyl ester (1). The novel derivative was characterized by both the conventional and linear polarized IR-spectroscopy of oriented colloid suspensions in nematic host, UV-spectroscopy, ¹H-NMR and mass spectrometry. The correlation between the structure and spectroscopic properties was estimated by using the known crystallographic data of the compound studied.     

方酸与某些偶氮化合物的反应

作为非苯系芳香性化合物和有机插烯二元酸,双功能性的方酸,可与许多亲核试剂反应并生成相应的双取代产物,通常都很难生成单取代产物。当它与芳环直接相连时会产生惊人的深色位移,这类化合物有诱人的应用前景。考虑到偶氮染料在染料工业中的作用和地位,我们试图在方酸衍生物中引入偶氮基,     

Environmentally benign process for the synthesis of N-formyl amino acid esters

Several amino acid ester hydrochlorides were reacted with ammonium formate to give N-formyl amino acid esters in good yields.     

Squaraines based on 2-arylpyrroles

Various derivatives of 2-phenylpyrrole were condensed with squaric acid to give the corresponding squaraines. The products are drawn with the anti geometry rather than the syn geometry generally shown in the past: the arguments for this formulation are given, including the analogy with 2,5-bis(4-ethyl-3,5-dimethylpyrrol-2-yl)-1,4-benzoquinone, for which an X-ray structure is presented. Solutions of the new bis(5-arylpyrrol-2-yl)squaraines have intense, sharp absorption bands shifted to the red. Condensation of squaric acid with arylpyrroles possessing fused ring systems, and condensation with 2-styrylpyrrole, gave chromophores with high values for λ_max and ?_max. Certain of these chromophores appear to be suitable for further structural elaboration to give materials having potential in optoelectronic and photodynamic applications.