Computational Approach to the Receptor-Bound Conformation of Cyclosporin A

The conversion of the conformation of cyclosporin A (CsA) observed in CHCl₃ to the receptor-bound state is investigated by two molecular-mechanics methods, template forcing and dynamic forcing. The conformations of CsA in CHCl₃ and complexed with LiCl in THF as determined by NMR are used as starting structures. The transition starting from the CsA/CHCl₃-derived conformation is hindered by steric interactions of two side chains (MeBmt¹ and Val⁵). While starting with the CsA/LiCl-derived conformation, the conversion is facile. It is illustrated that these calculations, which are of artificial character, using only the starting and final structures of the observed conformational transition during the receptor-binding event, allow an insight into the interactions between the substrates and receptor in terms of an induced fit.     

1-肼基-2,3-二氮杂萘盐酸盐的合成新方法

研究了l-肼基-2,3-二氮杂萘盐酸盐的合成新方法.以相对廉价易得的邻苯二甲酸酐为起始原料,依次通过还原、溴代、环合、取代、酸化等反应步骤得到目标产物1-肼基-2,3-二氮杂萘盐酸盐.研究表明该方法具有原料便宜易得、收率高、产物易分离纯化、后处理操作简单、总成本低等优点.     

A kinetics study of crystallization from discotic mesophases

The polymorphism of hexa- n -octanoate of rufigallol (RHO) was used to investigate the crystallization kinetics when starting from two different discotic mesophases, namely, a hightemperature enantiotropic mesophase and a low-temperature monotropic mesophase. In all cases, an Avrami exponent of n 3 was obtained, suggesting two-dimensional sporadic nucleation and growth. Although the same overall mechanism was predicted to operate for all crystallization temperatures investigated, the Avrami constant b has a temperaturedependence which is different for different starting columnar phases, indicating a strong influence on the rates of nucleation and of growth of the different molecular arrangements of the starting mesophases. Differential scanning calorimetry was used for the studies, supplemented by direct observations through optical polarizing microscopy.     

A Cu (I) catalyzed large scale synthesis of an antipsychotic drug substance Clozapine with new precursor 2-chloro benzoic acid

Development of an economic and commercial manufacturing process for an anti-psychotic drug substance clozapine with an alternative key starting material (2-chloro benzoic acid) in the place of literature reported key starting material Anthranilic acid. To avoid narcotic key starting materials usage in drug substances the author invented a commercially available raw material 2-chlorobenzoic acid, which reacts with another key starting material 4-chloro-1, 2-diamino benzene. This reaction proceeds through Ullman reaction to produce multi scale level Clozapine which quality meets the ICH requirements.     

A new synthetic approach to phenothiazine-2-amines

Elaboration of a Buchwald-Hartwig protocol for the introduction of amino functions to position 2 of the phenothiazine ring system has opened a new access to various N-alkyl and N-dienyl phenothiazines bearing secondary amines, tertiary amines, and amide moieties. Hydrolysis of the amido derivatives gave unsubstituted phenothiazine-2-amines. This protocol provides an easy access to phenothiazine-2-amines starting from the commercially available starting compounds.     

A new synthesis of biotin

(±)-Biotin is prepared starting from the new intermediate 3,4-diamino-2-carbomethoxy-thiophene.     

A short and highly stereoselective route to polyhydroxy-perhydroazaazulenes via a C-(d-galacto-pentopyranos-5-yl)isoxazolidine

A short and efficient route to enantiomerically pure hexahydroxy- and pentahydroxy-perhydroazaazulenes, ring-homologues of castanospermine, starting from the sole isoxazolidine derivative obtained in the 1,3-dipolar cycloaddition of a d-galactose-derived nitrone and methyl acrylate, is established. The procedure allows both backbone and stereochemical modulation of the products by choice of the starting monosaccharide. Structural assignment was based on crystallographic analysis of the starting isoxazolidine and NMR techniques. The products were tested for inhibitory activity against several glycosidases.     

A Convenient Sythesis of 1-Triacontamol,A Plant Growth Hormone

A synthesis of 1-triacontanol, a plant growth regulator, starting from myristic acid and by two successive additions of eight and nine carbon units from sebacic acid in Kolbe electro-organic process has been reported.     

A novel and efficient synthesis of L-vinylglycine

A simple and practical synthesis of the title compound starting with L-glutamic acid is described.     

A concise asymmetric route to the antibiotic macrolides patulolide A and pyrenophorin

In this letter, we describe an enantiospecific route to patulolide A and pyrenophorin through the synthesis of known protected seco acid precursors starting from commercially available (S)-ethyl lactate.     

A Ferrocenylsulfide-mediated Sulfur Ylide Epoxidation Reaction

A ferrocenylsulfides 1-2 mediated sulfur ylide epoxidation reaction was found to stereoselectively afford trans-oxiranes in excellent yields with recoverable starting material.     

A concise synthesis of meridianin F

A concise synthesis of the protein kinase inhibitor meridianin F has been achieved in good overall yield starting from 5,6-dibromoindole-3-carbaldehyde.     

A straightforward route to spiroketals

A straightforward route to 1,7-dioxa-, 1,4,7-trioxa- and 1,4,7,10-tetraoxaspiro[5.5]undecanes, starting from commercially available 3-chloro-2(chloromethyl)prop-1-ene, is described.     

A Morita-Baylis-Hillman adduct allows the diastereoselective synthesis of styryl lactones

We disclosed herein a diastereoselective approach for the total syntheses of (±)-Leiocarpin A and (±)-Goniodiol. These biologically active styryl lactones were obtained from a common intermediate, prepared in five steps and 40% overall yield, using a simple synthetic sequence starting from a Morita-Baylis-Hillman adduct. The total syntheses of these styryl lactones were accomplished in nine steps. This is the first report on the total synthesis of this class of natural products starting from Morita-Baylis-Hillman adduct.     

A Concise, metathesis based approach to construction of the lepadiformine/cylindricine tricyclic framework

A tandem dienyne metathesis based strategy has been developed for construction of the core tricyclic framework found in the lepadiformine and cylindricine alkaloids. 2-Pentenyl-2-ethynylpyrollidine acrylamide that serves as the starting material for the key ruthenium carbene catalyzed metathesis process is prepared by using a concise route starting with l-proline.     

A Convenient Access to Chiral Sulfonic Acids

Neomenthyl and trans myrtanyl sulfonic acids are obtained, free from inorganic salts, starting from the corresponding chiral alcohols.     

A Chiron Approach for the Total Synthesis of Crassalactone A

The total synthesis of crassalactone A ( 1 ) has been achieved in twelve steps starting from commercially available 1,5‐D ‐gluconolactone. Still? Gennari olefination, one‐pot deprotection, and lactonization are the key reactions involved in the synthesis.     

β-Stannylpropionaldehyde. A versatile cyclopropane building-block

Various functional group-substituted cyclopropanes were prepared in good yield starting from β-tributylstannylproprionaldehyde via homoallylstannanes or γ-hydroxypropylstannanes.     

A Novel Route to 1,2,4-Triazoles

A novel synthetic method for the synthesis of 1,2,4-triazoles have been described starting from 1,3,4-thiadiazoles by adsorbing on acidic alumina under microwave irradiations (MWI).     

4—O—乙基表鬼臼苦的一种简便制法

鬼臼毒素（1）是一种天然有机化合物，广泛存在于多种植物体内［‘j．人们已对其本身和衍生物的合成、理化性质、生理活性及立体结构等进行了深人研究，并相继开发出VP－16－ZI3、VM－26［’1等抗癌药物．我国具有丰富的鬼臼毒素资源，为了开辟利用鬼臼毒素资源的新途径，我们设想，将鬼臼毒素进行适当的结构修饰，使其转化成象6那样构型确定、具有双齿结构的二醇类及氨基醇类鬼臼毒素衍生物，以期望开发出一类新的手性配体，探索其在不对称合成中的应用．为此，我们需要大量的4－O一乙基表鬼臼苦（5）作为合成手性配体的中间体．据文献…