Access to piperidine imino-C-glycosides via stereoselective thiazole-based aminohomologation of pyranoses

The access to piperidine homoazasugars (dideoxyiminoheptitols) from pyranoses via formal one-carbon chain elongation and exchange of the ring oxygen with the NH group is described. The key process involves the stereoselective addition of 2-thiazolylmagnesium bromide to an N-glycosylhydroxylamine, i.e., a hidden open-chain sugar nitrone. The N-thiazolylalkylhydroxylamine formed in this way is reduced to amine, and this transformed into a substituted piperidine via intramolecular cyclization by an S(N)2 process. Cleavage of the thiazole residue attached to C2 of the piperidine ring reveals the formyl group, and this is reduced to hydroxymethyl to give the target homoazasugar. A collection of six stereodiversified compounds with free OH and NH groups and isolated as hydrochlorides has been prepared.     

Chemical modification of plant alkaloids. 6. T-reactions of anabasine derivatives

T-reactions of anabasine derivatives were performed for the first time. Condensation of 5-nitro-2-[2-(3pyridyl)piperidino]benzaldehyde with 1,3-dimethylbarbituric acid formed an annelated tetrahydroquinoline system containing a spiropyrimidine moiety as the T-reaction product. Condensation of this same aldehyde with Meldrum’s acid was accompanied by recyclization that led to opening of the piperidine ring and closing of the tetrahydroquinolone system. A third version of the T-reaction that also led to opening of the piperidine ring but without recyclization was the condensation with dimedone.     

多巴胺盐酸盐与二甲亚砜的相互作用研究

使用核磁共振技术、密度泛函理论(DFT)和分子中原子(AIM)理论,研究了多巴胺盐酸盐(DH)与二甲亚砜(DMSO)的相互作用。结果表明,DH中酚羟基和氨基正离子上的氢原子、苯环上位于酚羟基和侧链之间碳上的氢原子,甚至侧链上与苯环直接相连的亚甲基上的氢原子都可与DMSO中的氧原子形成分子间氢键。     

Asymmetric synthesis of acyclic 1,3-amino alcohols by reduction of N-sulfinyl beta-amino ketones. Formal synthesis of (-)-pinidinol and (+)- epipinidinol

Stereoselective reduction of acyclic N-sulfinyl beta-amino ketones with (LiEt(3)BH) and Li(t-BuO)(3)AlH, respectively, gave anti- and syn-1,3-amino alcohols with excellent selectivity. A formal asymmetric synthesis of the hydroxy piperidine alkaloids (-)-pinidinol and (+)-epipinidinol from a common N-sulfinyl beta-amino ketone ketal precursor was developed. The pinidinol piperidine ring was formed via a novel acid-catalyzed cascade reaction of a N-sulfinylamino silyl protected alcohol ketal.     

反式9, 10-二氢-9, 10-二苯基-9, 10-菲二醇包结性能的研究

合成了一种具有螯形结构的反式-9, 10-二氢-9, 10-二苯基-9,10-菲二醇(1)作为主体分子。它能与许多有机小分子化合物, 诸如DMF, DMSO, 吡啶, 哌啶, 喹啉, 异喹啉等形成包结化合物。本文还报道了这些包结化合物的IR, 粉末XRD的表征, 用^1H NMR谱测定了它们的分子摩尔比。DMF包结物的单晶四圆X衍射结果表明主体分子1与客体分子形成的包结物为配位笼状包合物。     

<Superscript>1</Superscript>H NMR spectroscopy in the study of the three-dimensional structure of 7-alkoxyalkyl-3-thia-7-azabicyclo-[3.3.1]nonan-9-ones and some of their derivatives

¹H NMR spectroscopy was used to establish that 7-alkoxyalkyl-3-thia-7-azabicyclo[3.3.1]nonan-9-ones and their decarbonylated derivatives in deuterochloroform solution exist in the double chair conformation. The predominantly formed secondary alcohols isomers have preferred double chair conformation with the hydroxyl group equatorial relative to the plane of the piperidine ring. On the other hand, the epimeric alcohols have predominant boat-chair conformation; the piperidine ring takes the boat form due to intramolecular hydrogen bonding between the unshared electron pair of the nitrogen atom and hydroxyl group proton. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1716–1725, November, 2008.     

A stereoselective approach to the synthesis of pseudodistomin D

A stereoselective total synthesis of the core unit of pseudodistomin D, starting from l-serine, is described. The key step is a stereoselective intramolecular Michael reaction in which the piperidine ring is formed with the obtention of 1.     

Tandem cross metathesis and intramolecular aza-Michael reaction to synthesize bicyclic piperidines and indolizidine 167E

We have successfully transformed the terminal alkenes of dihydropyridones to the α,β-unsaturated esters by cross metathesis (CM). After detosylation the secondary amides can undergo the intramolecular aza-Michael reaction to give the bicyclic piperidine structures. The stereoselectivity of the aza-Michael reaction is determined by the size of the newly formed ring. With simple transformations we have also achieved the synthesis of indolizidine 167E.     

Effect of Through‐Bond Interaction on Conformation and Structure in Rod‐Shaped Donor–Acceptor Systems. Part 2.

The crystal structures of seven N‐aryltropan‐3‐one (=8‐aryl‐8‐azabicyclo[3.2.1]octan‐3‐one) derivatives 1T1, 2T1, 2T2, 3T2, 5T2, 2T3 , and 3T3 are presented (Fig. 2 and Tables 1–5) and discussed together with the derivatives 1T2 and 4T2 published previously. The piperidine ring adopts a chair conformation. In all structures, the aryl group is in the axial position, with the plane through the aryl C‐atoms nearly perpendicular to the mirror plane of the piperidine ring. The through‐bond interaction between the piperidine ring N‐atom (one‐electron donor) and the substituted exocyclic C?C bond (acceptor) not only elongates the central C? C bonds of the piperidine ring but also increases the pyrimidalization at C(4) of the piperidine ring. Flattening of the C(2)–C(6) part of the piperidine ring decreases the through‐bond interaction.     

Nitrogen bridgehead compounds. Part 80 unusual reaction of ethyl 9-bromo-4-oxo-6,7,8,9-tetr ahydro-4h-pyrido[1,2-a]pyrimidine-3-carboxylates and N-Methylaniline

The acid-catalysed intramolecular nucleophilic addition of the phenyl ring to the C(9a) = N(1) double bond of ethyl 9-(N-methyl-N-phenyl)-4-oxotetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carboxylates, formed in the reactions of ethyl 9-bromo-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carboxylates and N-methylaniline, gave the first examples of a new tetracyclic pyrimido[1′,2′:1,2]pyrido[3,2-b]indole ring system ( 7 ). X-ray diffraction analysis of 7a revealed that the annelation of the pyrimidine and piperidine rings is transoid, while that of the piperidine and pyrroline rings is cis, the piperidine ring adopts an unusual ⁶T₈ twisted boat conformation, while the pyrroline ring has a ⁹T_8a conformation.     

配体结构对含2-甲基咪唑及N-乙基咪唑的NAMI 衍生物水解及溶液稳定性的影响

制备并用UV、循环伏安(CV)和NMR 法研究了NAMI(新抗肿瘤转移抑制剂, trans-[RuCl₄(DMSO)(imidazole)]Na·2DMSO)衍生物trans-[RuCl₄(DMSO)(2-MeIm)]Na·2DMSO (2-MeIm＝2-甲基咪唑, 化合物1)和trans-[RuCl₄(DMSO)-(N-EtIm)]Na·2DMSO (N-EtIm＝N-乙基咪唑, 化合物2)的水解机理-动力学、溶液稳定性和电化学性质. 化合物1 和化合物2 与NAMI 相似, 在pH 7.40 的缓冲溶液中发生两步脱氯水解反应(I 氯水解及II 氯水解) (分步反应); 在酸性溶液(pH 5.00)中脱DMSO 水解. 通过线性拟合得到各水解反应速率常数k_obs 及半衰期t_1/2. 结果表明化合物在酸性溶液中的稳定性相对较高. 在NAMI 衍生物咪唑环的N 位引入乙基比在2 位引入甲基生成的化合物稳定. 含氮配体相同时,NAMI-A(新抗肿瘤转移抑制剂, A: 该系列中的第一个化合物, trans-[RuCl₄(DMSO)(imidazole)][Himidazole])衍生物略比相应的NAMI 衍生物稳定.     

Stereocontrolled synthesis of quinine and quinidine

Disubstituted cyclopentene was prepared from cyclopentene monoacetate and transferred into disubstituted piperidine via oxidative cleavage of the olefin moiety followed by piperidine ring formation. The piperidine was then condensed at the side chain with a quinoline part to afford the olefin precursor of quinine. Finally, the olefin was converted into quinine through the corresponding epoxide. Quinidine was synthesized in a similar way.     

Thermodynamics of complex formation in dimethyl sulfoxide with ligands coordinating via N,P, As,Sb, OR Bi : III. A comparison between aromatic and aliphatic amines and phosphines

The stabilities of the complexes formed by silver(I), cadmium(II) and zinc(II) with tri-n-butylamine and tri-n-butylphosphine have been determined in dimethyl sulfoxide (DMSO). For the two latter metal ions, it has also been found that complexes are not formed in appreciable amounts with the triphenyl compounds Ph₃X, X = N, P and, in the case of cadmium(II), also As.From these and earlier measurements referring to DMSO as well as aqueous solutions, it was found that the stepwise stability constants increase by roughly one power of ten for each aromatic ring replaced by an aliphatic group, evidently as a consequence of the improved donor properties of the coordinating atoms. Further, for ligands of the same type, the stabilities are always markedly lower in DMSO than in aqueous solution. This is certainly due to the fact that the solvent molecules compete more strongly for the coordination sites in DMSO than in water, as reflected by the larger heats of solvation found in the former solvent for the metal ions concerned.     

Reactions of 1,2,4,5-Tetrafluoro-3,6-bis(vinylsulfonyl)benzene with Cyclic Amines

Reactions of 1,2,4,5-tetrafluoro-3,6-bis(vinylsulfonyl)benzene with pyrrolidine, piperidine, and morpholine lead to formation of different products, depending mainly on the reactant ratio. In the presence of 2 equiv of cyclic amine, adducts at both vinylsulfonyl groups are formed, while in reactions with 4 equiv of cyclic amine, the addition at the double bonds is accompanied by nucleophilic replacement of one or two fluorine atoms in the benzene ring.     

The Mechanism of Schiff Base Formation of Some Arylidenes-p-Aminosalicylic Acid

Formation of a series of Schiff bases derived from p-aminosalicylic acid I and various aromatic aldehydes has been studied kinetically in ethanol medium in presence of piperidine as a basic catalyst. The order of the reaction is determined to each reactant by following the concentration of the Schiff base formed during the reaction. The reaction is Kinetically third-order in the presence of low concentration of piperidine, first-order to each of I , aldehyde and piperidine. On the other hand, in presence of ≥5×10^?4 M of piperidine the order of the reaction changed to second-order, thus much the reaction is independent of piperidine concentration. The rate determining step is suggested to be the dehydration of the carbinolamine intermediate step 4. Variation in reaction rate constants with the different substituent of the aromatic aldehyde, with substituents of aromatic amine and with the nature of the hydroxylic organic solvents as reaction medium are studied and discussed.     

Synthesis and Structure of the Clusters [Hg2(μ—SePh)2(SePh)2(PPh3)2] and [Hg3Br3(μ—SePh)3] · 2 DMSO

The compounds [Hg₂(μ—SePh)₂(SePh)₂(PPh₃)₂] ( I ) and [Hg₃Br₃(μ—SePh)₃] · 2 DMSO ( II ) are formed by reactions of [Hg(SePh)₂] with PPh₃ in THF( I ) or with HgBr₂ in DMSO ( II ) at room temperature. X—ray crystallography reveals that the cluster I consists of a distorted square built by each two Hg and Se atoms. The Hg atoms have almost tetrahedral co‐ordination environments formed by selenium atoms of two (μ‐^—SePh) ligands and Se and P atoms of terminal ^—SePh and PPh₃ ligands. The compound II is a six‐membered ring with alternating Hg and Se atoms in the chair conformation. Two DMSO molecules occupy positions below and above the [Hg₃Se₃] ring with the oxygen atoms directed to the centre of the ring.     

芬太尼类化合物的分子静电势研究

本文应用INDO波函数计算了三个芬太尼类化合物的分子静电势。酰胺氧原子周围均存在一个势阱很深的宽广的负电势区域, 是最重要的负电中心。 哌啶环4-位引入甲氧甲基后,增加了新的负电势区域。哌啶环1-位芳环周围具有宽广的正电势区域。 哌啶氮原子和酰胺氮原子附近存在较小的负电势区域。 基于计算出的静电势推测了三个化合物的镇痛作用的可能机理及药物结构与毒性的关系。     

A neutral,isolable covalent adduct between piperidine and a troponoidal phosphonium salt: A peculiar acylphosphorane

The phosphonium salt obtained by P-methylation of 2-diphenyl-phosphinotropone with methyl iodide was found to undergo C-7 addition by piperidine, and loss of hydrogen iodide, to give an acylsphosphorane which could be isolated; the regiospecificity of piperidine addition was proven by deuterium labeling at the troponoid ring.     

双哌啶基二硫化物的动态NMR的研究

双取代哌啶基二硫化物的动态^1H NMR谱的研究表明,分子内哌啶环的翻转活化自由能较哌啶有显著增加,△G值为71.43±0.25-73.27±0.46kJ.mol^-^1,同时观察到双哌啶基二硫化物分子内哌啶环的3,4,5-位所在平面的翻转,比1,2,6-位所有在平面约快四倍,△G值低3.62kJ.mol^-^1;这充分显示了分子中N原子上带有较大基团的影响.比较双哌啶基二硫化物与相应三硫化物的环翻转能垒,也显示出空间障碍的影响.     

Isomeric effect in the self-assembly of pyridine-containing L-glutamic lipid: substituent position controlled morphology and supramolecular chirality

Three isomeric pyridine-containing L-glutamic lipids formed organogels in DMSO and self-assembled into different nanostructures of nanofiber, nanotwist and nanotube depending on the substituent position in the pyridine ring.