Total synthesis of (+/-)-kainic Acid with an aza-[2,3]-Wittig sigmatropic rearrangement as the key stereochemical determining step

A flexible route to the kainoid skeleton is exemplified by the synthesis of (+/-)-kainic acid from 3-butyn-1-ol. The route relies on the aza-[2,3]-Wittig sigmatropic rearrangement to efficiently install the relative stereochemistry between C2-C3. The C4 stereocenter was derived from a diastereocontrolled iodolactonization. The aza-[2,3]-Wittig rearrangement potentially allows structural diversity at C3 and the displacement of the tosyloxy group with retention of stereochemistry allows structural diversity at C4. The trans-C2 carboxylic acid functional group was found to be the most important for retention of stereochemistry at C4 upon treatment with a higher order cyano cuprate reagent.     

Azacrown ethers containing oximic and Schiff base sidearms - potential heteronuclear metal ion receptors

A simple synthetic pathway for the preparation of oxime- and Schiff base-containing aza- and diazacrown ethers is reported. N-Methoxymethyl-substituted aza-15-crown-5 and aza-18-crown-6 as well as N,N′-bis(methoxymethyl)-substituted diaza-18-crown-6 were treated with 5-bromosalicylaldehyde to produce the N-(2′-hydroxy-3′-carbonyl-5′-bromobenzyl)-substituted aza-15-crown-5 (8), aza-18-crown-6 (9) and N,N′-bis(2′-hydroxy-3′-carbonyl-5′-bromobenzyl)-substituted diaza-18-crown-6 (10) compounds. Compounds 8 and 10 were treated with hydroxylamine to give oxime-substituted ligands 12 and 13. A series of bis-Schiff base-containing diaza-18-crown-6 ligands were prepared by reacting 10 with 2-hydroxyaniline (to form 14), 5-nitro-2-hydroxyaniline (15), 2-aminopyridine (16), 2-hydrazinopyridine (17) and N-aminomorpholine (18). Compounds 12–18 are potential complexing agents for simultaneous binding of soft transition and hard alkali or alkaline earth metal ions in one molecule. These new oxime- and Schiff base-containing ligands interacted strongly with Na⁺ and K⁺ in methanol. The interaction of the aromatic portions of 9, 10, and 12–15 with transition metal ions was shown by the UV spectra of the metal ion complexes in 50% aqueous DMF. The X-ray structure of 10 is reported.     

An intramolecular aza-[3+3] annulation approach to azaphenalene alkaloids. Total synthesis of myrrhine

A detailed account on the stereoselective total syntheses of azaphenalene alkaloids via an intramolecular aza-[3+3] annulation strategy is described here. All five members of the Coccinellidae family of defensive alkaloids were prepared from the same common intermediate, which was derived from a stereoselective aza-[3+3] annulation reaction.     

A convenient synthesis of functionalized 8- and 9-aza-1-oxaspiro[5.5]undecanes

2-Hydroxy-8-(or 9-)aza-1-oxaspiro[5.5]undec-3-en-5-ones derived from their corresponding 2-furfuryl alcohols were used as key intermediates for the convenient synthesis of several novel 8- and 9-aza-1-oxaspiro[5.5]undecane derivatives.     

Asymmetric aza-[2,3]-Wittig sigmatropic rearrangements: chiral auxiliary control and formal asymmetric synthesis of (2S, 3R, 4R)-4-hydroxy-3-methylproline and (-)-kainic acid

A survey of 16 different chiral auxiliaries and a variety of strategies found that an (-)-8-phenylmenthol ester of a glycine derived migrating group can control the absolute stereochemistry of aza-[2,3]-Wittig sigmatropic rearrangements with diastereoselectivities of ca. 3 : 1 with respect to the auxiliary. In two specific examples, ca. 50% yields of enantiomerically pure products were obtained after chromatographic purification. These were synthetically manipulated with no erosion of stereochemistry into intermediates that completed formal asymmetric syntheses of (+)-HyMePro and (-)-kainic acid.     

DFT, ab initio, NMR, and NBO analyses of N-substituted hydrazino acetamides: Experimental vs theoretical values

We studied the DFT (B3LYP) and HF at 6-31+G/6-31+G^∗∗ levels of theory in order to throw light on the conformation, structure, intramolecular hydrogen bond network, as well as proton and nitrogen NMR (GIAO method) of a series of model primary amides in the gas phase and/or in solution (chloroform, methanol, water, dimethyl sulfoxide, and heptane). In this manner, it was possible to show that the amidic group of these model compounds acts as the H-bond donor and interacts with two different H-bond acceptors, thus stabilizing the C₈ pseudocycle. The study was conducted to gain a better understanding of the conformation (both experimentally and theoretically) adopted by hydrazino acetamides (model compounds for aza-β³-peptides). In the light of this, we were able to explain why aza-β³-peptides develop a different H-bond network in comparison to their isosteric β³-peptide analogues (an extension of the β-peptide concept).     

Total synthesis of (+)-lepadin F

An enantioselective total synthesis of (+)-lepadin F is described. The synthetic sequence features an intermolecular aza-[3 + 3] annulation, homologation of a vinylogous amide via Eschenmoser's episulfide contraction, and a highly stereoselective hydrogenation essential for achieving the 1,3-anti relative stereochemistry at C2 and C8a.     

Preparation of new monomers aza-β-aminoacids for solid-phase syntheses of aza-β-peptides

The preparation of new N^β-Fmoc-protected aza-β³-amino acids (aza-β³-aa) with proteinogenic side chains as well as their N^β-Fmoc, N^β-Cbz or N^β-Boc aza-β³-amino esters (from Pro, Asn, Asp, Glu, Gln) by successive nucleophilic substitutions will be described.     

Indolizines and Their Hetero/Benzo Derivatives in Reactions of [8+2] Cycloaddition

Peculiarities of [8+2] cycloaddition of acetylenes to indolizines are reviewed. Especially mentioned are indolizines with leaving groups at positions 3 and 5. Cycloaddition to aza- and benzo derivatives are reviewed, as well as 1,10-cyclizations and processes leading to cyclazines where indolizines are intermediates. Mechanistic features (adducts and cycloadducts) and theoretical aspects (one- or two-steps mechanism) are reviewed.     

Molecular Complex Formation between Some Azacrown Ethers and 2,4,6-Trinitrophenol

The formation of molecular complexes with 1 : 1 stoichiometry between 2,4,6-trinitrophenol and aza-12-crown-4, aza-15-crown-5 and aza-18-crown-6 in chloroform solution was investigated spectrophotometrically. The resulting complexes were isolated and characterized by microchemical analysis, IR and NMR spectroscopy. The equilibrium constants of the 1 : 1 adducts were evaluated from the non-linear least-squares fitting of the absorbance-mole ratio data. The overall stability of the 2,4,6-trinitrophenol complexes was found to vary in the order aza-15-crown-5 > aza-18-crown-6 aza-12-crown-4. The kinetics of complex formation between 2,4,6-trinitrophenol and the aza-substituted crown ethers used were investigated and in all cases the results showed the occurrence of an oscillating chemical reaction in solution.     

Diastereoselective synthesis of substituted prolines via 5-endo-trig cyclisations of aza-[2,3]-Wittig sigmatropic rearrangement products

The major diastereoisomers of aza-[2,3]-Wittig sigmatropic rearrangement products from α-amino acid derivatives are susceptible to a rare nucleophilic 5-endo-trig cyclisations of an amine onto a non-conjugated vinylsilane in high yield and complete diastereocontrol. Five examples are presented, with cyclisation yields between 35 and 87%. A rationale for the stereoselectivity of the cyclisation is forwarded based upon the steric control factors that have been documented for the aza-[2,3]-Wittig sigmatropic rearrangement. A discussion of the mechanism in the context of the reaction conditions is also presented. Oxidation of the silyl group to a hydroxyl group and complete removal were demonstrated for synthetic utility.     

三岔共轭体系中的结构效应-氮杂查耳酮类与碘乙烷的反应动力学

本文用电导法研究了4＇-苯多烯酰基吡啶化合物4 pOnB中吡啶基的化学活性。反应动力学数据表明,4pOnB与碘乙烷在丙酮溶液中为二级反应,相关系数r均大于0.995。共轭主链的长度(n)对反应活化能的影响不大,这表明三岔共轭体系中基干结构的共轭作用不能通过三岔点影响吡啶环上氮原子的电子云密度。三岔共轭体系中较短的一支分岔与三岔体系中的共轭基干结构是互相隔离的,仅起代基作用。     

Tetronamides as latent acyclic vinylogous amides in formal aza-[3 + 3] cycloaddition reactions with alpha,beta-unsaturated iminium salts. An unexpected rearrangement and an approach to synthesis of substituted piperidines

A detailed account regarding formal aza-[3 + 3] cycloaddition reactions of tetronamides with alpha,beta-unsaturated iminium salts is described here. This investigation uncovers regioisomeric cycloadducts that were not found in previous studies involving this formal cycloaddition and an unexpected rearrangement that led to pyridines and dihydropyridines. Both stereochemical and regiochemical issues raised in this study provide further mechanistic insights into this cycloaddition. With careful control of reaction temperatures, the desired formal cycloadducts are obtained. Ensuing transformation of these cycloadducts into functionalized piperidines establishes the concept of employing tetronamides as latent acyclic vinylogous amides for the formal aza-[3 + 3] cycloaddition.     

Relative bond strengths in tetrahedrane,prismane, and some of their aza analogs

Ab initio molecular orbital calculations at the 3–21G level have been employed to explore structures, bond order, and bond deviation indices for a series of aza- and diazatetrahedranes and aza-, diaza-, triaza-, and tetraazaprismanes as well as their hydrocarbon analogs. The introduction of nitrogens has the effect of strengthening C-C and some of the N-C bonds, while the presence of N-N bonds introduces a decrease in relative thermodynamic stability in the aza-prismane series.     

多功能基和氮杂冠醚键合固定相的制备与鉴定

在全多孔微粒硅胶表面进行连续固－液相反应,制备氯丙基（ＣＰＳ）、乙二醇氨丙基（ＤＥＡＰ）、３－［氮杂１８－冠－６］－丙基（ＢＣＰ）键合固定相。采用有机元素分析、功能基分析、热分析、红外光谱和金属离子络合容量测定等对键合相进行鉴定和表征。化学和仪器分析结果表明,键合反应按预定路线进行。键合固定相具有各种色谱性能,其极性效应对分离选择性起重要作用。     

Synthesis and biological evaluation of 1,4-naphthoquinones and quinoline-5,8-diones as antimalarial and schistosomicidal agents

Improving the solubility of polysubstituted 1,4-naphthoquinone derivatives was achieved by introducing nitrogen in two different positions of the naphthoquinone core, at C-5 and at C-8 of menadione through a two-step, straightforward synthesis based on the regioselective hetero-Diels-Alder reaction. The antimalarial and the antischistosomal activities of these polysubstituted aza-1,4-naphthoquinone derivatives were evaluated and led to the selection of distinct compounds for antimalarial versus antischistosomal action. The Ag(II)-assisted oxidative radical decarboxylation of the phenyl acetic acids using AgNO(3) and ammonium peroxodisulfate was modified to generate the 3-picolinyl-menadione with improved pharmacokinetic parameters, high antimalarial effects and capacity to inhibit the formation of β-hematin.     

Synthesis of actinomycin D analogs: XXIII. Actinocin derivatives containing azacrown fragments

A number of actinocin amides containing residues of aza-15-crown-5 and aza-18-crown-6 where crown fragments were separated from the heterocyclic chromophore by the residues of ω-amino acids were obtained as actinomycin D models.     

Asymmetric synthesis of suitably protected γ-hydroxy-aza-β3-homothreonine building blocks

An efficient and easily applicable method for the enantioselective synthesis of γ-Hydroxy aza-β³-homothreonine (aza-β³-Hyht) has been established. The method involves stereoselective reductive amination of glyoxylic acid and the corresponding Fmoc protected chiral hydrazine. A stereoselectivity of 99% was achieved for each step using (R)-2,3-O-isopropylideneglyceraldehyde as the chiral auxiliary. This new synthetic monomer is a useful building block for the solid-phase synthesis of new peptidomimetics.     

Synthesis and Characterization of New Phthalocyanines Peripherally Fused to Four 13-Membered Tetrathiamacrocycles

The new metal-free phthalocyanine 5 and phthalocyaninatometals 6–8 (M=Co, Ni, or Zn) fused in peripheral positions with four 13-membered tetrathiamacrocycles were prepared by cyclotetramerization of 2, 3, 6, 7, 9, 10-hexahydro-5H-[1, 4, 8, 11]benzotetrathiacyclotridecine-13, 14–dicarbonitrile in the presence of a suitable metal salt or a strong organic base. In contrast to the aza- or oxamacrocycle-fused analogs, the solubility of these phthalocyanines is very low. Complexation of the tetrathiamacrocycles of 7 and 8 with Pd^II or Ag^I to form pentanuclear products was accomplished from their suspensions.     

三氟甲基侧取代氧、氮、硫杂大环化合物的合成和 分子结构

合成了四个三氟甲基侧取代氧、氮、硫杂大环化合物,通过IR、^1HNMR、RS和元素分析作了表征;用AM1方法计算它们的电子结构,并根据计算结果给出了它们的几何构型。