Isolation,Structure, and HIV‐1 Integrase Inhibitory Activity of Xanthoviridicatin E and F,Two Novel Fungal Metabolites Produced by Penicillium chrysogenum

HIV‐1 Integrase is a critical enzyme for replication of HIV, and its inhibition is one of the most promising new drug targets for anti‐retroviral therapy with potentially significant advantages over existing therapies. Xanthoviridicatins E ( 1 ) and F ( 2 ) are two novel polyketide natural products that were isolated from a fermentation broth of an endophytic strain of Penicillium chrysogenum isolated from the living leaves collected in Peru. These compounds are new members of the unsymmetrical xanthoviridicatin family represented by the broader xanthomegnin family. Xanthoviridicatins E and F inhibited the cleavage reaction of HIV‐1 integrase with an IC₅₀ of 6 and 5 μM , respectively. The bioassay‐directed isolation, structure elucidation, and HIV‐1 inhibitory activity of these compounds are described.     

Construction of the 17-Thiasteroid Ring System by the Diene-Sulfur Dioxide Cycloaddition Reaction

Abstract

We recently showed² that the steroid ring system can be constructed with a phosphorus atom replacing a carbon in the D-ring by the cycloaddition of a phosphorus (III) halide with a diene that is a vinyl dihydrophenanthrene derivative, such as (1). The phosphine oxide (3) resulting from the hydrolysis of the initial cycloadduct (2) has some resemblance to the hormone equilenin, which also has rings A and B in naphthalene form.     

Proximally functionalized cavitands and synthesis of a flexible hemicarcerand

A general study on the synthesis of partly bridged octols3a-d and4c-d is described. Tri-bridged diol3c can be prepared in 54% yield in DMSO at 70°C with excess CH₂BrCl or in 52% yield in DMF at 70°C with only 4 equiv. of CH₂BrCl. 1,3-Di-bridged tetrol4a, one of the two possible di-bridged isomers formed in preference to the other, was obtained in 30% yield. Tri-bridged diols3c andd can be selectively debrominated in one step by treatment with 5 equiv. ofn-BuLi in THF to afford the corresponding dibromo derivatives8a andb in 77% and 76% yields, respectively. After incorporation of the fourth bridge, the remaining two bromines can be replaced by C(O)OMe to give9c (60%), by OH to give9d (62%) or by CN to give9f (>95%). When the lithiated derivatives of3c andd are quenched with electrophiles other thanH ⁺, a selectively functionalized tri-bridged diol with hydroxyl (8c, 47%) and selectively functionalized cavitands with thiomethyl (9g, 25%) or iodo (9h, 20%) groups can be synthesized. Two molecules of9d were coupled with CH₂BrCl in DMSO/THF under high dilution conditions to give the flexible hemicarcerand10 in 71% yield. Supplementary Data. A list of observed and calculated structure factors have been deposited with the British Document Supply Centre as Supplementary Publication No. SUP 82170 (50 pages)This paper is dedicated to the commemorative issue on the 50th anniversary of calixarenes.     

An Aminated GDP-Fucose Analog Useful in the Fucosyltransferase Catalyzed Addition of Biological Probes onto Oligosaccharide Chains1

Abstract

An analog (1) of GDP-fucose, where C-6 is derivatized with an eight-atom spacer terminating in a primary amino group, was chemically synthesized. This amino group in sugar nucleotide 1 can be acylated using an N-hydroxysuccinimide ester of biotin and it can be coupled to another molecule that also contains an amino group using squaric acid diethyl ester as the coupling reagent. In this way, biotin and a blood group A-active trisaccharide were linked to C-6 of fucose in GDP-fucose. Both complex sugar nucleotides thus prepared were active as donors for a human milk fucosyltransferase, which transferred the derivatized α-linked fucose residue to a glycoside of N-acetyllactosamine, thus labeling this sequence with either biotin or the blood-group A trisaccharide. Compound 1 is proposed as a general and versatile reagent which should permit the addition of biological probes to the sugar chains of cell surface glycoproteins or glycolipids.     

Synthesen und Reaktionen von Pyridazinderivaten, 11. Mitt.: 5-Acyl-4-pyridazincarbonsäurrester als „key intermediates” für 4-Acylpyridazine und 4-Alkyl-bzw. 4-Arylpyridazino[4,5-d]pyridazin-1 (2H) one

A convenient general method of preparing 4-acylpyridazines (4) is reported. It involves homolytic acylation of ethyl-4-pyridazinecarboxylate yielding ethyl-5-acyl-4-pyridazinecarboxylates (2) which easily can be converted to4 by alkaline hydrolysis followed by decarboxylation. The hitherto unknown pyridazino[4,5-d]pyridazine-1 (2H) ones bearing an alkyl- or arylsubstituent on C-4 (5a-g) were prepared in quantitative yields by reaction of2 with hydrazine.

10. Mitt.:G. Heinisch, A. Jentzsch undI. Kirchner, Tetrahedron Lett.1978, 619.     

Simple Infrared Cell for Corrosive Gases

Abstract

A simple infrared cell that can be used for corrosive gases is described. The cell consists of a Kel-F tube with silver chloride windows sealed on with Kel-F wax. Evacuation of the cell to 10^?5 mm is possible.     

Efficient Synthesis of Aryl Hydroxylactams by Reducing Imides With Activated Zinc Dust

A series of aryl hydroxylactams (2a, 2b, 2d–2g, 2i–2k, 2m, and 2n) was synthesized by partially reducing aryl cyclic imides in moderate to excellent yields with activated zinc dust alone in acetic acid. This method was regiospecific and can be employed as an alternative for reported methods to partially reduce aryl cyclic imides.     

A Piezoelectric Crystal Detector for Acetoin

Abstract

A piezoelectric quartz crystal coated with tetrabutyphosphoniun chloride was found to be a good detector for acetoin. The coating is sensitive in the ppb range and completely reversible. The response curve is linear over a concentration range of 8-120 ppb. The detector can be tuned to give a satisfactory response in 30 seconds.     

Total Synthesis of (±)-Armepavines and (±)-Nuciferines From (2-Nitroethenyl)benzene Derivatives

A concise route to armepavine 1 and nuciferine 2 and 3, which can be isolated from the leaves of Nelumbo nucifera (Nymphaceae), has been achieved in which the longest linear sequence is only six steps from commercially available benzaldehyde in 28%, 21%, and 20% overall yield, respectively. The key transformations in the synthesis are the radical cyclization of aryl bromide with Bu₃SnH and the Pictet–Spengler reaction of N-substituted amine with aldehyde.     

ESR Titration of AS2O3 by Potassium Permanganate

Abstract

A rapid esr titration method is described and demonstrated with the As₂O₃/KMnO₄ system. The results indicate that end points can be established with a precision of better than 1% and an accuracy of 0.4%.     

不同氟取代基对苝酰亚胺电子迁移率的影响

利用空间电荷限制电流(SCLC)法测试了二种氟代苝酰亚胺的电子迁移率, 一种是N,N'-二(五氟代苯基)-3,4,9,10-苝四羧基二酰亚胺(1), 另一种是N,N'-二(1,1-二氢十五氟代辛基)-3,4,9,10-苝四羧基二酰亚胺(2). 结果发现, 化合物2的电子迁移率要比1高1～2个数量级. UV-Vis, XRD, SEM和AFM等表征手段证明, 这一现象可以用不同的氟取代基导致不同的聚集态结构来解释: 对于化合物1而言, 苯环平面与苝环平面之间存在大的夹角, 破坏了苝酰亚胺分子的平面性, 再加上刚性的氟代苯环大的空间位阻作用, 化合物1分子无法依靠相邻苝环之间的重叠排列而结晶, 只能无序堆积形成非晶膜; 与之相反, 在化合物2分子中苝环上的端基是柔性的锯齿状氟代烷基链, 空间位阻小, 化合物2分子能通过相邻苝环之间相互接近而形成的π-π偶合作用而结晶, 因此有利于电子在苝酰亚胺分子间的跳跃传输.     

Beiträge zur Chemie der Pyrrolpigmente, 78. Mitt.: Die Eigenschaften desb-Nor-bilatrien-abc-b-Nor-biladien-ac-Systems

The redox coupleb-nor-biladiene-ac (2)/b-nor-bilatriene-abc (3) exhibits an oxidative half wave potential of 800 mV in acetonitrile solution. It is demonstrated that it can be used as an extremely efficient electron carrier through bulk membranes. Whereas2 is not suitable as a ligand in carrier mediated cation transport,3 is a medium suited carrier for Cu(II) or Zn(II) ions, however, it is the most efficient one found so far for transport of Hg(II) ions. A 1:1 zinc chelate of3 is isolated and characterized. it is deduced to represent a polymer consisting of about 73 monomer units.

     

Microwave‐Assisted Protection of Phenols as tert‐Butyldimethylsilyl (TBDMS) Ethers Under Solvent‐Free Conditions

Abstract

A facile, time‐saving procedure to protect phenols with tert‐butyldimethylsilyl chloride using imidazole as catalyst under solvent‐free conditions is described. Several phenolic compounds with different substitution patterns can be silylated in high yield with substantially reduced generation of residues, a present goal in organic synthesis.     

3-Hydroxythiazole and 1-Hydroxyimidazole as Products of a Mutual Ring Closure Reaction: Extension to Selenium Derivatives

A thiazole derivative can be easily prepared, e.g., from an α -thiocyanatoketone and a nitrogen nucleophile. In this work, α -bromopropiophenone was chosen as a starting compound. Since the carbonyl group facilitates nucleophilic substitution, bromine can be simply replaced with the thiocyanato group. The following reaction with hydroxylamine hydrochloride provides an intermediate, which undergoes a ring closure reaction. Finally, 3-hydroxy-5-methyl-4-phenylthiazol-2(3H)-iminium chloride 4a or 1-hydroxy-4-methyl-5-phenyl-1,3-dihydro-2H-imidazole-2-thione 5a arises depending on the presence of a base. In the next part, this interesting phenomenon was successfully investigated on selenium derivatives as well. All prepared substances have not been described in the literature yet.     

Synthese von Dibenzo[a,g]chinolizinen — Ein neuer Zugang zu Protoberberinen

Summary A novel synthesis to prepare dibenzo-8-quinolizinones8 is reported using the intramolecular cyclisation of the benzylated Reissert compounds6 for the key step. Methylation of8 by methyllithium gives partial deoxygenated coralynes10 which in turn can be reduced by NaBH₄ yielding the 8-methyltetrahydro-protoberberines11. The structures are assigned by NMR-spectroscopy.

     

A facile method for the synthesis of free-standing pillar[5]arene-based two-dimensional covalent organic monolayers in solution

ABSTRACT

This report describes a facile method by which, without using any surface-assisted growth or pre-organisation, free-standing two-dimensional (2D) covalent organic monolayers (COMs) were synthesised through condensation reactions of planar tri-aldehydes with A1/A2-diamino-substituted pillar[5]arene (DAP5). In the as-formed monolayers (DAP5-COM-1 and DAP5-COM-2), the tubular pentagonal pillar[5]arene units positioned out of the 2D polymer planes suppress efficiently the interlayer π-π stacking interactions. Both DAP5-COM-1 and DAP5-COM-2 can be transferred onto solid surfaces for further characterisation and were found to possess unusual fluorescence up-conversion property.     

联二噻吩稠合的近红外BODIPY染料的合成与光谱性质

以叠氮乙酸乙酯和联二噻吩甲醛为原料,合成了联二噻吩并吡咯单体,之后在酸催化下与4-N,N-二甲基氨基苯甲醛缩合并与三氟化硼配位,得到一个新型的BODIPY染料SY。采用~1HNMR、质谱以及元素分析对其结构进行了表征。化合物SY在二氯甲烷中的最大吸收和发射波长分别为654和689nm;采用荧光光谱滴定方法研究了它对pH值的响应,酸性条件下N,N-二甲基苯氨基团发生质子化,抑制了光诱导电子转移对BODIPY母体的荧光淬灭,其溶液的荧光显著增强,染料SY可以作为近红外的pH值荧光探针。     

联二噻吩稠合的近红外BODIPY染料的合成与光谱性质

以叠氮乙酸乙酯和联二噻吩甲醛为原料,合成了联二噻吩并吡咯单体,之后在酸催化下与4-N,N-二甲基氨基苯甲醛缩合并与三氟化硼配位,得到一个新型的BODIPY染料SY。采用¹H NMR、质谱以及元素分析对其结构进行了表征。化合物SY在二氯甲烷中的最大吸收和发射波长分别为654和689 nm;采用荧光光谱滴定方法研究了它对pH值的响应,酸性条件下N,N-二甲基苯氨基团发生质子化,抑制了光诱导电子转移对BODIPY母体的荧光淬灭,其溶液的荧光显著增强,染料SY可以作为近红外的pH值荧光探针。     

A Simple Method Involving Aqueous Two-Phase Separation-Systems for Activity Determination of Enzymes Hydrolyzing Macromolecular Substrates

Abstract

A new general procedure for quantitation of enzymes degrading macromolecular substrates is described. With the use of chromogenic substrates combined with separation of substrate and product by aqueous two-phase systems, rapid separation and accurate measurements can be achieved.

Furthermore, in competitive substrate assays using constant amounts of enzyme and chromogenic substrate in combination with a varying amount of native substrate, unknown concentrations of native substrate can easily be determined.

The principle is illustrated here by a system consisting of the enzyme, dextranase; the chromogenic substrate, blue dextran; and the native substrate, dextran.     

On the experimental technique of X-ray diffraction in liquid crystals

Abstract

A modified freely suspended film method is described. Sample alignment can be achieved either by spontaneous ordering or by applying an electric or a magnetic field. Conventional X-ray equipment can be used.