Total Synthesis of Siomycin A: Completion of the Total Synthesis

The total synthesis of siomycin A ( 1 ), a representative compound of the thiostrepton family of peptide antibiotics, was achieved by incorporating the five synthetic segments A ( 2 ), B ( 3 ), C ( 4 ), D ( 5 ), and E ( 6 ). The dehydropiperidine segment A ( 2 ) was esterified with the dihydroquinoline segment C ( 4 ), and the subsequent coupling with the β‐phenylselenoalanine dipeptide segment D ( 5 ) at the segment C portion followed by lactamization between the segments A and D gave segment A‐C‐D ( 27 ). This was amidated with the pentapeptide segment B ( 3 ) at the segment A portion followed by one‐pot cyclization (between segments A and B) and elongation (with the β‐phenylselenoalanine dipeptide segment E ( 6 ) at the segment A portion), thus furnishing siomycin A ( 1 ).     

Preparation of S-acetylthioglycoloyl insulins based on separation by anion-exchange high-performance liquid chromatography.

A method for the preparation of insulin derivatives having protected sulfhydryl group(s) on definite site(s) on the molecule which uses anion-exchange high performance liquid chromatography on a TSKgel DEAE-2SW column for separation is described. Porcine insulin reacts with N-succinimidyl S-acetylthioacetate to afford four species of insulin derivatives that have S-acetylthioglycoloyl group(s) at: i) Gly(A1), ii) Gly(A1) and Phe(B1), iii) Gly(A1) and Lys(B29), and iv) Gly(A1), Phe(B1) and Lys(B29) positions. An insulin derivative which has a group at the Lys(B29)-position is prepared by the S-acetylthioglycoloylation of Gly(A1), Phe(B1)-dicitraconyl insulin followed by decitraconylation. The five derivatives are readily deacetylated with hydroxylamine to yield the corresponding sulfhydryl insulin derivatives.     

Conversion of D-glucose to cyclitol with hydroxymethyl substituent via intramolecular silyl nitronate cycloaddition reaction: application to total synthesis of (+)-cyclophellitol

[reaction: see text] A diastereoisomeric mixture of 1-nitro-6-heptene-2,3,4,5-tetraol derivative (A) was prepared by Henry reaction between d-glucose-based aldehyde and nitromethane. Only the (2S)-isomer of A led to cyclitol (B) via nitronate-olefin cycloaddition on treatment with TMS-Cl and Et(3)N in the presence of catalytic DMAP followed by acid treatment. (+)-Cyclophellitol (1) was synthesized from B in eight steps.     

Regioselective quinazolinone-directed ortho lithiation of quinazolinoylquinoline: practical synthesis of naturally occurring human DNA topoisomerase I poison luotonin a and luotonins B and E

A regioselective quinazolinone-directed ortho lithiation on an adjacent quinoline moiety has been used as a key step for a short, efficient, and practical synthesis of the human DNA topoisomerase I poison luotonin A and luotonins B and E. The quinazolinoylquinoline 5 on treatment with in situ-generated nonnucleophilic mesityllithium furnished the desired dilithiated intermediate 6, which on treatment with formaldehyde followed by Mitsunobu ring closure reaction gave luotonin A (1a) in very good yield. The reaction of dilithiated intermediate 6 with DMF directly furnished luotonin B (1b) in 81% yield. Luotonin B (1b) on methylation with p-TSA/methanol gave luotonin E (1c) in 82% yield.     

Total synthesis of everninomicin 13,384-1--Part 3: synthesis of the DE fragment and completion of the total synthesis

The stereoselective construction of the DE fragment (2) of everninomicin 13,384-1 (1) is reported. From the two possible ways of inserting the DE fragment between the A1B(A)C and FGHA2 domains of the natural product, the sequence involving the DEFGHA2 segment was found to be the most viable. This coupling was followed by attachment of a suitably protected and activated A1B(A)C fragment which led, after orthoester construction and final deprotection to the targeted everninomicin 13,384-1 (1), completing the total synthesis of this complex naturally occurring substance.     

Synthesis of entadamide A and entadamide B isolated from Entada phaseoloides and their inhibitory effects on 5-lipoxygenase

Two new sulfur-containing amides, entadamide A (1) and entadamide B (2), isolated from the seeds of Entada phaseoloides, were synthesized by the addition reaction of methanethiol to propiolic acid (5) followed by condensation with ethanolamine by the use of dicyclohexylcarbadiimide. These compounds inhibited the 5-lipoxygenase activity of RBL-1 cells at 10(-4) g/ml. This finding suggests that entadamides A and B may be examples of a new type of antiinflammatory drug.     

Pafuranones A and B,two dimeric polyketides from a rare marine algae-derived fungus Paraconiothyrium sp.

A pair of dimeric polyketide epimers formed through conjugate addition and intramolecular lactonization were identified from the culture of a rare marine algae-derived fungus, Paraconiothyrium sp. OUCMDZ-3316.     

Reactivity of digermylenes toward potassium graphite: synthesis and characterization of germylidenide anions

The synthesis and characterization of the digermylenes [LGe-GeL] [L = L(1) (3A), L(2) (3B)] supported by the 2,6-diiminophenyl (L(1)) and 2-imino-5,6-methylenedioxylphenyl (L(2)) ligands are described. Their reactivities toward potassium graphite are also reported. The reaction of [LGeCl] [L = L(1) (2A), L(2) (2B)] with KC(8) in tetrahydrofuran (THF) at room temperature afforded the digermylenes [LGe-GeL] [L = L(1) (3A), L(2) (3B)], which are the first examples of diaryldigermylenes stabilized by o-imino donor(s). The treatment of 3A with 2 equiv of KC(8) in Et(2)O, followed by the addition of excess tetramethylethylenediamine (TMEDA), results in cleavage of the Ge(I)-Ge(I) bond to afford the germylidenide anion [L(1)GeK·TMEDA] (4A). Similarly, the reaction of 3B with excess KC(8) in THF afforded the germylidenide anion [L(2)GeK] (4B). The molecular structures of compounds 4A and 4B as determined by single-crystal X-ray diffraction analysis show that the K atoms are η(1)-coordinated with the low-valent Ge atoms. Moreover, the negative charges at the Ge atoms in compounds 4A and 4B are stabilized by electron delocalization in the germanium heterocycles.     

Determination of carotenoids in tomato juice by liquid chromatography

A high-performance liquid chromatography method was developed to determine the various carotenoids in tomato juice. A C30 column and a mobile phase of acetonitrile-1-butanol (7:3, v/v) (A) and methylene chloride (B) with the following gradient elution were used: 99% A and 1% B intitally, increased to 4% B in 20 min, 10% B in 50 min and returned to 1% B in 55 min. Sixteen carotenoids, including all-trans-lutein, all-trans-beta-carotene, all-trans-lycopene and their 13 cis isomers were identified and resolved within 52 min with flow-rate at 2.0 ml/min and detection at 476 nm. Of the various extraction solvent systems, the best extraction efficiency of carotenoids in tomato juice was achieved by employing ethanol-hexane (4:3, v/v). Lycopene was found to be present in largest amount in tomato juice, followed by beta-carotene and lutein.     

Synthesis of 4,4-disubstituted piperidine analogs of (±)-cis-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide

Condensation of (±)-1-benzyl-3-methyl-4-piperidone ( 1 ) with aniline followed by trapping of the intermediate imine with cyanide generated a mixture of isomeric nitriles 2A and 2B , the structures of which were established unambiguously by obtaining an X-ray crystal structure on nitrile 2B . Subsequent elaboration of the nitrile intermediates provided analogs of (±)-cis-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide having a second substituent (carbomethoxyl, carboethoxyl, methoxymethyl) at the piper-idine 4-position. The conversion of the carboxamide intermediates 3A and 3B to the carboalkoxyl intermediates 5A, 5B and 6A was accomplished utilizing a modified esterification procedure. Proton nmr data are presented for both the final products and the key synthetic intermediates.     

免疫亲和萃取-超高效液相色谱-串联质谱法分离测定中成药及中药材中的5种黄曲霉毒素

利用免疫亲和萃取结合超高效液相色谱-串联四极杆质谱技术(UHPLC-ESI/QqQ-MS/MS)建立了中成药及中药材中5种黄曲霉毒素(B1、B2、G1、G2和M1)的提取、分离、确证与定量方法。样品经80%(体积分数)的甲醇水溶液提取和免疫亲和固相萃取后,采用UHPLC-ESI/QqQ-MS/MS的多反应监测模式实现分离、鉴定和外标法定量。5种目标毒素标准溶液的检出限(LOD)为0.05～0.3 μg/L。在0.5～100 μg/L的基质添加浓度范围内具有良好的线性关系(r2＞0.99);以甘草为例,当添加水平为1.0 μg/kg和5.0 μg/kg时,得到62.3%～82.4%的回收率(相对标准偏差(RSD)＜10%, n=6)。该方法灵敏度高、选择性和重复性好、回收率较高、检测速度快,适用于中成药及中药材等复杂基体中多种黄曲霉毒素的快速分析与筛查。     

A total synthesis of methylenomycin B

A new synthesis of methylenomycin B (1) has been accomplished in four steps starting with a NI(CO)₄ promoted cyclocondensation reaction of allyl chloride and 2-butyn-1-ol in MeOH, followed by hydrogenolysis of the resulting mixture to 2,3-dimethyl-5-methyl-oxycarbonylmethyl-2-cyclopentenone (3), which by hydrolysis and oxidative decarboxylation yielded 1.     

Synthesis,coordination to Rh(I), and hydroformylation catalysis of new beta-aminophosphines bearing a dangling nitrogen group: an unusual inversion of a Rh-coordinated P center

Variants of the beta-aminophosphine L(1) [Ph(2)PCH(2)CH(Ph)NHPh] containing additional nitrogen donor functions have been prepared. These functions are branched off the C atom adjacent to the P atom, or the P atom itself. Ligand [Ph(2)PCH(o-C(6)H(4)NMe(2))CH(Ph)NHPh] has been obtained as a mixture of two diastereomers L(3A) and L(3B) by lithiation of L(2) [Ph(2)PCH(2)(o-C(6)H(4)NMe(2))] with n-BuLi followed by PhCH=NPh addition and hydrolysis. The diastereomers have been separated by fractional crystallization from ethanol. Ligand Et(2)NCH(2)P(Ph)CH(2)CH(Ph)NHPh has been obtained as a mixture of two diastereomers L(5A) and L(5B)(starting with P-Ph reductive cleavage of L(1) by lithium and subsequent hydrolysis to give PhP(H)CH(2)CH(Ph)NHPh (mixture of two diastereomers L(4A) and L(4B)). The latter reacts with diethylamine and formaldehyde to afford the L(5) diastereomeric mixture. Complexes RhCl(CO)(L) (L = L(3A), 1(A); L(3B), 1(B); L(5A/B), 2(A/B)) were obtained by reaction of [RhCl(CO)(2)](2) and the appropriate ligand or ligand mixture. Complexes 1(A), 1(B), and 2(A) have been isolated in pure form and characterized by classical techniques and by single-crystal X-ray diffraction. All structures exhibit a bidentate kappa-P,kappa-N(NHPh) mode similar to the complex containing L(1). While complexes 1(A) or 1(B) are stable in CDCl(3) solution, complex 2(A) slowly converts to its diastereomer 2(B). This unexpected epimerization appears to take place by inversion at the Rh-coordinated P center, an apparently unprecedented phenomenon. A mechanism based on a reversible P-C bond oxidative addition is proposed. The influence of the pendant nitrogen function of the diaminophosphines L(3A) and L(5A/B) on the rhodium catalytic activity in styrene hydroformylation has been examined and compared to that of the aminophosphines L(1) or L(2). The observed trends are related to the basicity of the dangling amine function and to its proximity to the metal center.     

Synthesis of (+)-zerumin B using a regioselective singlet oxygen furan oxidation

A short and efficient synthesis of the antitumor diterpenoid (+)-zerumin B has been accomplished starting from (+)-sclareolide. At the heart of the synthetic strategy lies the regioselective formation of the alpha-substituted gamma-hydroxybutenolide moiety of zerumin B. This was achieved by means of a [1,4] O-->C triisopropylsilyl migration followed by singlet oxygen (1 O 2) oxidation of the resulting 2-triisopropylsilyl-3-(alpha-hydroxy)alkylfuran.     

Total synthesis of everninomicin 13,384-1--Part 1: retrosynthetic analysis and synthesis of the A1B(A)C fragment

In this first of a series of four articles we introduce everninomicin 13,384-1 (1), a powerful antibiotic effective against drug resistant bacteria, as a target for total synthesis and discuss its retrosynthetic analysis. From the three defined fragments required for the synthesis (2: A1B(A)C fragment; 4: DE fragment; 5: FGHA2 fragment), we describe herein two approaches to the A1B(A)C block. The first strategy relied on an olefin metathesis reaction to construct a common intermediate for rings B and C, but was faced with final protecting group problems. The second, and successful approach, involved a 1,2-phenylsulfeno migration and a sulfur directed glycosidation procedure to link rings B and C, as well as an acyl fluoride intermediate to install the sterically hindered aryl ester moiety (ring A1). The final stages of the synthesis of the required 2-phenylseleno glycosyl fluoride 2 required introduction of a phenylseleno group at C-1 of ring C followed by a novel, DAST-promoted 1,2-migration to produce the desired 2-beta-phenylseleno glycosyl fluoride moiety.     

A simple oxidation of formycin to oxoformycin and oxoformycin B. Synthesis of 6-methyloxoformycin,A C-nucleoside analog of doridosine

A simple, high-yield procedure has now been developed for the direct oxidation of formycin to oxoformycin and oxoformycin B. Treatment of formycin (1) with bromine/water provided oxoformycin (8) . A similar treatment of formycin B (4) gave oxoformycin B (6) . Upon prolonged exposure of either 1 or 8 to bromine/water at reflux temperature, conversion to 6 occurred in good yield. Application of this procedure to 1-methylformycin (2) , 1-methylformycin B (5) and 2-methylformycin (17) gave 1-methyloxoformycin (9) , 1-methyloxoformycin B (7) and 2-methyloxoformycin (18) , respectively. Deamination of 8 and 9 with nitrosyl chloride also gave 6 and 7 , respectively. This selective oxidation of 6-methylformycin gave 7-amino-6-methyl-3-β-D-ribofuranosylpyrazolo[4,3-d]pyrimidin-5(4H)-one (10) , a C-nucleoside analog of doridosine. A similar oxidation of 1,6-dimethylformycin B (11) gave 1,6-dimethyloxoformycin B (12) . This direct introduction of the 5-oxo function into the pyrazolo[4,3-d]pyrimidine ring appears to be due to the attack of Br⁺ at N(4), followed by the addition of water to C(5) and subsequent elimination of hydrogen bromide from the transient intermediate 3 .     

Microwave-mediated Claisen rearrangement followed by phenol oxidation: a simple route to naturally occurring 1,4-benzoquinones. The first syntheses of verapliquinones A and B and panicein A

The naturally occurring 1,4-benzoquinones 2-methoxy-6-propyl-1,4-benzoquinone (1), 2-methoxy-6-pentyl-1,4-benzoquinone (primin 2), 2-methoxy-6-pentadecyl-1,4-benzoquinone (3), 2-methoxy-6-heptadecyl-1,4-benzoquinone (dihydroirisquinone, pallasone B; 4) were synthesized by a simple protocol involving microwave accelerated Claisen rearrangement of allyl ethers 10, followed by hydrogenation of the side chain alkene, and oxidation to the quinone. The Claisen-based methodology was extended to the first synthesis of the marine benzoquinones verapliquinones A and B (5 and 6), and panicein A (7). Isoarnebifuranone (9) was also synthesized by a similar strategy.     

苯并异噻唑啉酮类化合物的合成与活性研究

通过烷基醇与固体三光气(BTC)反应后加入1,2-苯并异噻唑啉-2(3H)-酮(BIT)继续反应的“一锅法”制备了8种未见文献报道的2-(苯并异噻唑啉-3-酮-2-基)甲酸酯类化合物.化合物结构经IR、1HNMR和元素分析确认,并且对枯草芽孢杆菌、金黄色葡萄球菌、嗜水单细胞菌和大肠杆菌进行了初步抑菌活性实验,实验结果表...     

Pd/C-Mediated Arylation Followed by I2-Catalyzed Hydration Strategy: Preparation of Functionalized Novel Indanone Derivatives

A simple and inexpensive synthesis of novel 2-(3-oxo-3-arylpropyl)-2,3-dihydro-1H-inden-1-one derivatives has been achieved via Pd/C-mediated arylation followed by I₂-mediated regioselective hydration of 2-(prop-2-ynyl)-2,3-dihydro-1H-inden-1-ones. A wide variety of 3-aryl substituted 2-propynyl indanone derivatives were conveniently prepared by using 10% Pd/C-PPh₃-CuI as a catalyst system, some of which were used to prepare the corresponding ketones via alkyne hydration in the presence of catalytic I₂. In an in vitro study a representative compound showed inhibition of PDE4B (phosphodiesterase type 4B) and binding with this protein in silico     

Study of the physicochemical properties of tulobuterol dry syrups using taste and smell sensors

The purpose of the present study was to evaluate the taste and smell of Tulobuterol Dry Syrup (TB-DS) in its original form (formulation A) and generic form (formulations B and C) by means of gustatory sensation tests and taste and smell sensors. In addition, the physicochemical properties of the syrups in a solid state were compared. Evaluation of sweetness with a powdered sample revealed significant differences between formulation A and formulation B and between formulation B and formulation C. In contrast, the results of principal component analysis (PCA) with a taste sensor revealed differences in principal component 1 (PC 1) among formulations A, B, and C. Smell sensor measurement of powdered samples revealed differences in products in terms of only PC 1, but these results were not related to the results of gustatory sensation testing with a smell sensor. Measurement of particle size distribution and scanning electron microscopy revealed differences in the particle diameter and particle surface shape for each product. Formulation B had the strongest absorption in the near-infrared spectrum, followed by formulation A and then formulation C. Accordingly, differences in preparations were presumably caused by variations in manufacturing specifications, such as types of additives and their content and coating methods used. In other words, the characteristics of each product were revealed by evaluation of their physical properties, sensing of taste and smell, and human gustatory sensation tests.