Expeditious access to (−)-shikimic acid derivatives for Tamiflu synthesis

A three-step, one-pot process has been developed for the synthesis of 5-epi-shikimic acid derivative 5 using inexpensive and abundant d-ribose as the starting material. Based on this pivotal intermediate, the syntheses of two key shikimic acid derivatives 6 and 7 for Tamiflu have been achieved in a concise and practical fashion.     

The enantioselective synthesis of APTO and AETD: polyhydroxylated beta-amino acid constituents of the microsclerodermin cyclic peptides

The polyhydroxylated beta-amino acids (2S,3R,4S,5S,7E)-3-amino-8-phenyl-2,4,5-trihydroxyoct-7-enoic acid (APTO) and (2S,3R,4S,5S,7E,9E)-3-amino-10-(4-ethoxyphenyl)-2,4,5-trihydroxydeca-7,9-dienoic acid (AETD) are key components of the microsclerodermin family of anti-fungal cyclic peptides. They have been synthesised in protected form in twelve steps using a unified strategy, with the introduction of the unsaturated sidechain in the final step of the synthesis from a common aldehyde intermediate. The synthesis features the ordered application of asymmetric aminohydroxylation and dihydroxylation reactions to efficiently introduce the stereochemistry of the targets with high selectivity.     

A concise synthesis of (R)- and (S)-α-alkyl isoserines from d- and l-malic acids

A simple and diastereoselective method for the synthesis of (R)- and (S)-α-alkyl isoserines has been developed in four steps starting from commercially available d- and l-malic acid, respectively. This approach features stereocontrolled alkylation of 2-(2-tert-butyl-5-oxo-1,3-dioxolan-4-yl)acetic acid and proceeds through a methylcarbamate via a Curtius rearrangement.     

Optically isotropic mesophase in comb-shaped copolymers with side mesogenic groups

Two series of comb-shaped copolymers poly(4-(4-cyanobiphenyl-4′-yloxy)butyl acrylate)-co-(4-(6-acryloyloxyhexyl-1-oxy)isophthalic acid)) and poly(4-(6-acryloyloxyhexyl-1-oxy)benzoic acid)-co-(acrylic acid)) have been prepared by free-radical copolymerization, and their phase diagrams have been constructed. Formation of the optically isotropic phase characterized by the absence of birefringence and high optical activity has been demonstrated for a number of copolymers. At the same time, the DSC curves of these compounds show a well-defined phase transition with the heat of melting equal to 2–5 J/g. Specific features of hydrogen bonding in the copolymers have been studied by IR spectroscopy. It has been speculated that there is correlation between microphase separation between hydrophobic and hydrophilic units in the copolymers and formation of the optically isotropic mesophase.     

Self-assembled 1,2-bis[4-(4-(10-decyloxy)phenylazo)]benzoylhydrazine dimer and its hydrogen-bonded complexes

We report the synthesis and investigation of a new self-assembled benzoylhydrazine-based compound, namely 1,2-bis[4-(4-(10-decyloxy)phenylazo)]benzoylhydrazine and their hydrogen-bonded complexes with different carboxylic acid derivatives, of which some exhibit liquid crystalline properties and some are non-mesogens. The conversion of the non-liquid crystalline target compound that is free from carboxylic acid to liquid crystalline complexes containing various carboxylic acids can probably be rationalised through the breaking of intermolecular hydrogen bonding within the supramolecular assembly by carboxylic acid dopants. The enhancement of liquid crystalline properties of benzoylhydrazine compounds with respect to various carboxylic dopants is documented. Other salient features can be exemplified by the formation of discotic columnar phase as shown by the azo-linkage containing 4-(4′-(10-decyloxy)phenylazo)benzoic acid-doped complex.     

一种新型锰MOF的合成、结构和磁性的研究

通过水热合成法以1-(4羧苯基)-1H-苯并咪唑-5,6-二羧酸为配体合成了一种新型金属锰MOF[Mn(Hcbic)]n(H3cbic=1-(4羧苯基)-1H-苯并咪唑-5,6-二羧酸),并通过X-ray进行了单晶分析.该Mn-MOF是包含了一维左、右双螺旋链,螺距约为0.3902 nm,同时配体Hcbic2-中的4-...     

Production of antibodies from chicken egg yolk to phenyl- N -methylcarbamate insecticides for analytical purposes

With the aim of developing polyclonal antibodies binding as many phenyl-N-methylcarbamate insecticides (PNMCs) as possible, IgY antibodies were produced in laying hens. Two haptens (3-(2,6-dimethyl-4-(methylcarbamoyl)phenylaminocarbonyl)propanoic acid and 4-((2,6-dimethyl-4-(methylcarbamoyl)phenylaminocarbonyl)-3,3-dimethyl)butanoic acid) were synthesized preserving the major structural features of PNMCs, by a novel synthetic pathway. These haptens differed only in the spacer arm incorporated. Immunizing antigen and coating antigen were prepared by coupling the first hapten with bovine serum albumin and the second with thyroglobulin, from porcine thyroid glands, respectively. The titre and maturation increase in the developed antibodies, in the egg yolk, were assessed by non-competitive ELISA. Avidity and cross-reactivity of the antibodies with selected pesticides were estimated by means of competitive ELISA. The produced IgYs exhibited a high binding capacity to carbaryl, trimethacarb, metolcarb, aminocarb, and promecarb. These antibodies can be used for immunosorbent preparation for analytical purposes.     

Synthesis and Properties of Sulfophenyl-Substituted Metal Phthalocyanine Complexes

Sulfonation of 4-phenylphthalic acid gave 4-(p-sulfophenyl)phthalic acid triammonium salt which was used in the synthesis of tetra[4-(p-sulfophenyl)]phthalocyanine copper and cobalt complexes by the urea method. The products were characterized by elemental analyses and ¹³C NMR, IR, and electronic spectra. Some specific features of the electronic spectra of sulfophenyl-substituted metal phthalocyanines were revealed, depending on the central metal atom, solvent nature, and concentration.     

Synthesis and structure of novel 1lambda4,2,6-thiadiazines

S,S-Disubstituted sulfodiimines 9 are known to be versatile building blocks for the synthesis of various sulfur-nitrogen-containing heterocycles. Addition-condensation reactions of 9 with three different activated carbonylsubstrates 14-16 lead to several new 1lambda(6),2,6-thiadiazine-3-ones 17-20. S-Debenzylation via a novel synthetic approach utilizing different electrophiles such as TMSCl, Alk(3)O(+)BF(4)(-), Tos(2)O, and Mes(2)O gives rise to a variety of so far hardly known 1lambda(4),2,6-thiadiazine-3-ones 25 and 26. Structure elucidation reveals NH/CH tautomers in solution as well as a tetrahedral asymmetric sulfur attached to the conjugated planar N/C skeleton. The structural features of the 1lambda(4),2,6-thiadiazines 25 and 26 as well as their reactivity toward certain electrophiles will be discussed in detail. Alkylation with Alk(3)O(+)BF(4)(-) preferably results in formation of the 3-alkoxy-1lambda(4)-2,6-thiadiazines 29. In the presence of acid or base, also the N-2-alkyl isomers 30 are formed. Mesylation of 26 with methanesulfonic acid anhydride followed by aminolysis furnishes a variety of the desired heterocycles 5 in moderate overall yield.     

Investigation of the low-frequency vibrations of crystalline tartaric acid using terahertz spectroscopy and solid-state density functional theory

The room temperature and cryogenic terahertz (THz) spectra (10-95 cm(-1)) of l-tartaric acid and dl-tartaric acid were investigated. At 293 K, the l-tartaric acid spectrum showed four absorption features at 36.4, 61.6, 78.7, and 87.3 cm(-1) in the experimental spectrum. Once cooled to 78 K, these features narrowed and shifted to 35.9, 63.4, 81.1, and 90.1 cm(-1). The THz spectrum of dl-tartaric acid is significantly different, containing only a single absorption at 79.9 cm(-1) at room temperature, which shifts to 82.9 cm(-1) at 78 K. Solid-state density functional theory calculations [B3LYP/6-311G(2d,2p)] were performed to simulate the crystalline structure of both molecular solids and to assign the observed spectral features to specific atomic motions. The THz spectrum of l-tartaric acid is particularly interesting in that it contains a theoretically unaccounted for spectral feature that may arise from second-order phonon processes and also exhibits an anomalous red-shifting absorption feature with cooling that is shown to originate from negative thermal expansion of the crystal.     

High-resolution spectroscopy of H2SO4, HDSO4, and D2SO4 vapor in the region 1200-10,000 cm(-1)

The high-resolution (0.05 cm(-1)) spectra of gas-phase H2SO4, HDSO4, and D2SO4 were measured over the frequency region 1200-10,000 cm(-1) using Fourier-transform infrared spectroscopy. The increased resolution of this work compared with previous studies has lead to an improved vibrational analysis of H2SO4. This study has answered unresolved questions about combination bands and overlapping features from previous gas-phase spectroscopic studies of H2SO4 and marks the first experimental measurement of the nu8 and nu15 torsional vibrations in this molecule. This work leads to a brief discussion on vibrational mode mixing in sulfuric acid.     

Synthetic analogues of Peganum alkaloids. III. Pentamethylenequinazolones

Monosubstituted 5-, 6-, and 8-methoxy-3,4-dihydro-2,3-pentamethylenequinazolones (1–3) have been syntehsized by the condensation of monosubstituted methoxyanthranilic acids with caprolactam. Demethylation with hydrobromic acid gave the corresponding hydroxy compounds [4–6]. When the 6- and 8-methoxy- and 6- and 8-hydroxy-3,4-dihydro-2,3-pentamethylenequinazolones (2, 3, 5, and 6) were reduced with zinc in hydrochloric acid, the corresponding quinazoline derivatives (7–10) were obtained. The melting points of the basis and their hydrochlorides are given. Some features of their UV, mass, and PMR spectra are reported.     

Total synthesis of mycalamide A

This communication describes a concise and efficient total synthesis of mycalamide A by the convergent coupling of pederic acid unit with the mycalamine unit. The left-half, (+)-7-benzoylpederic acid, was synthesized from (2R,3R)-3-methylpent-4-en-2-ol in seven steps and 34.6% overall yield through a route that features a one-step Pd(II)-catalyzed tandem Wacker/Heck cyclization reaction to prepare the tetrahydropyran ring system. The right-half, the mycalamine unit, was synthesized in 21 steps and 10.5% overall yield from diethyl d-tartrate. Effective, stereoselective methods were developed for the assembly of the two parts to yield either mycalamide A or C(10)-epi-mycalamide A.     

IR plus vacuum ultraviolet spectroscopy of neutral and ionic organic acid monomers and clusters: propanoic acid

The vibrational spectrum of molecular propanoic acid, cooled in a supersonic expansion, in the region of 2500 to 7500 cm(-1) is obtained employing infrared plus vacuum ultraviolet nonresonant ionization detected spectroscopy. The fundamental and first overtone of the CH and OH stretch modes of cold propanoic acid molecules can be identified in the spectrum. Propanoic acid neutral and ionic clusters are also studied employing nonresonant ion dip and photodissociation spectroscopic techniques, respectively. For the neutral dimer, a sequence of features observed at ca. 2500-2700 cm(-1) can be assigned as combination bands of low frequency modes with the COH bending overtone; these features characterize the cyclic dimer ring structure. IR spectra of the larger neutral clusters n=3, 4, 5 indicate that they also have cyclic structures in which the OH groups are engaged in the cluster hydrogen bonding network. The CH groups are not involved in this hydrogen bonding structure. Free OH features are observed for the protonated ion clusters (C(2)H(5)COOH)(n)H(+), n=1,...,5, indicating that at least one OH group of these cluster ions is not involved in the cluster hydrogen bonding network. A comparison of the results for four hydrogen bonding neutral and ionic clusters (CH(3)OH, C(2)H(5)OH, CH(3)COOH, and C(2)H(5)COOH) is presented and discussed.     

苯磺酸贝他斯汀的合成新方法

探索了一条合成苯磺酸贝他斯汀的新路线。以2-吡啶甲酸、氯苯为原料，经过9步反应合成苯磺酸贝他斯汀，其中关键消旋中间体(4-氯苯基)(2-吡啶基)甲氧基哌啶，经过D-DBTA拆分，可得到光活性(S)-(4-氯苯基)(2-吡啶基)甲氧基哌啶(>99% ee)。同时，(R)-(4-氯苯基)(2-吡啶基)甲氧基哌啶经过消旋化后再次拆分得到(S)-构型产物。该合成方法反应条件温和，具有工业化生产前景。最终产物结构由¹H NMR， ¹³C NMR和HR-MS(ESI)确证。      

Total synthesis of (-)-salinosporamide A

A concise and stereoselective total synthesis of (-)-salinosporamide A (1), a potent inhibitor of the 20S proteasome that is in clinical development as an anticancer drug candidate, has been accomplished in 14 steps with 19% overall yield from 4-pentenoic acid. Our synthesis features a stereoselective alkylation utilizing a chiral auxiliary, formation of a pyrrolidine unit, and oxidation of the pyrrolidine to a γ-lactam. To demonstrate the scalability of our synthesis, (-)-salinosporamide A has been synthesized on a gram scale.     

Reaction of 3,4-dioxohexane-1,6-dioic acid esters with 2,4-dinitrophenylhydrazine

Reaction was studied of 3,4-dihydroxyhexa-2,4-diene-1,6-dioic acid esters with 2,4-dinitrophenylhydrazine that led to the formation of esters of (3E)-3-[2-(2,4-dinitrophenyl)-hydrazinylidene]-4-oxohexane-1,6-dioic and (3E,4E)-3,4-bis[2-(2,4-dinitrophenyl)hydrazinylidene]-hexane-1,6-dioic acids. The structural features of compounds synthesized were established from the data of IR and NMR spectra and X-ray diffraction (XRD) analysis.     

Synthesis of phenylacetylene containing 1,2,3-triazole group

Bromination of (E)-1-[4-(2-carboxy-vinyl)phenyl]-[1,2,3]triazole-4-carboxylic acid ethyl ester, which was synthesized in 90% yield by a Huisgen-type [3 + 2]-cycloaddition reaction between 3-(4-azidophenyl) acrylic acid and ethyl propiolate, in CHCl₃ followed by a debrominative decarboxylation reaction with Et₃N in DMF under microwave irradiation condition afforded stereoselective (Z)-1-(4-(2-bromovinyl)phenyl)-1,2,3-triazole-4-carboxylic acid ethyl ester in 94% yield. Treatment of (Z)-1-(4-(2-bromovinyl)phenyl)-1,2,3-triazole-4-carboxylic acid ethyl ester with EtONa in DMF afforded 1-(4-ethynylphenyl)-1,2,3-triazole-4-carboxylic acid ethyl ester in a yield of 90%.     

Synthesis of 2-O-(4-coumaroyl)-3-(4-hydroxyphenyl)lactic acid, an important intermediate of rosmarinic acid biosynthesis.

A simple method to synthesize (+/-)-2-O-(4-coumaroyl)-3-(4-hydroxyphenyl)lactic acid (1), a key intermediate in rosmarinic acid biosynthesis in higher plant cells, was established by condensation of protected 4-coumaric acid and (+/-)-3-(4-hydroxyphenyl)lactic acid followed by deprotection. A stable supply of 1 thus attained will lead to biochemical and molecular biological characterization of later steps of rosmarinic acid biosynthesis.     

A concise route to a key intermediate in the total syntheses of (+)-tirandamycic acid and (-)-tirandamycin a 2

An efficacious, asymmetric synthesis of the 2,9-dioxabicyclo[3,3,1]nonane 4 has been completed in nine chemical steps from 4,5-dimethylfuraldehyde (8). Since enantiomerically pure 4 has been previously converted in five steps by Ireland into (+)-tirandamycic acid (3) and more recently by Schlessinger into (-)-tirandamycin A (1), this achievement constitutes in a strictly formal sense the total syntheses of these substances. The key step in the synthesis of 4 features the transformation of the enantiomerically pure furfuryl diol 25 into 29 by initial selective oxidation of (the furan ring and subsequent acid-catalyzed bicycloketalization.