Synthesis of novel 5-oxaprotoberberines as bioisosteres of protoberberines

5-Oxaprotoberberinones and 5-oxaprotoberberinium were synthesized as bioisosteres of protoberberines. 5-Oxaprotoberberinones were prepared by linking phenol with the isoquinolone ring of 3-phenolisoquinolones by methyleneoxy bridge, while the quaternary 5-oxaprotoberberinium salt was synthesized by reduction and oxidation of the lactam moiety of 5-oxaprotoberberinone.     

An efficient palladium-catalyzed synthesis of 1-heteroaryl-4-aminopiperidine derivatives from heteroaryl chlorides

An efficient protocol for the synthesis of 1-heteroaryl-4-(N-methyl)aminopiperidines starting from heteroaryl chloride derivatives is described. A broad range of 1-heteroaryl-4-(N-Boc-N-methyl)aminopiperidine derivatives were obtained in good to excellent yields using DavePhos as optimal ligand for Pd-catalyzed Buchwald-Hartwig amination reaction. After a mild and efficient acidolysis the amination products could be obtained successfully.     

Synthesis of pyrazole derivatives as potential bioisosteres of thromboxane-synthetase inhibitors

A series of ω-carboalkenyl pyrazole derivatives have been synthesized as potential thromboxane-synthetase inhibitors considering the close bioisosteric relationship between the pyrazole ring and other heteroaromatic carboalkenyl compounds exhibiting inhibitory activity. (E)-7-(1-Phenylpyrazol-4-yl)hept-2-enoic acid (4b) were prepared in 28% overall yield from its minor bis-homologue, (E)-5-(1-phenylpyrazol-4-yl)pent-2-enoic acid (4a) , obtained from 4-formyl-1-phenylpyrazole (6) in 17% overall yield. Compounds 4a, 4b, 7, 8 and 13 were screened for their ability to inhibit the in vitro rabbit blood platelet aggregation induced by collagen using the Born test. Among the active compounds 4a exhibited an important inhibition at 1 μM concentration.     

Synthesis of functionalized furopyrazines as restricted dipeptidomimetics

Herein, an efficient synthetic approach to a furopyrazine scaffold with four points of diversity, starting from 2(1H)-pyrazinones, with dipeptomimetic properties, is presented. R-groups corresponding to amino acid side chains were introduced during the 2(1H)-pyrazinone and subsequent furopyrazine formation. The furopyrazine scaffold was further functionalized with an amino- and a carboxy-terminus resulting in a conformationally restricted dipeptidomimetic scaffold. The carboxy-terminus was introduced via a chemoselective vinylation of the 7-position followed by oxidative cleavage, while the amino-terminus was obtained via Buchwald–Hartwig amidation of the 2-position of the scaffold. The versatility of the synthetic method was demonstrated by the synthesis of a small library of diversely substituted furopyrazines having various amino acid side chains on the four points of diversity. Evaluation with an X-ray structure of the scaffold and computational analysis supports the exploitation of the furopyrazine scaffold as a restricted dipeptide mimic, which can mimic the two central residues of a β-turn.     

Improved synthesis of functionalized 5,6-dihydro-pyrimido[4,5-b][1,4]oxazepines

Novel synthetic approaches toward 5,6-dihydro-pyrimido[4,5-b][1,4]oxazepines were reported that led to successful introduction of poorly reactive anilines and various 2-hydroxybenzaldehydes to this therapeutically relevant scaffold. More extensive SAR studies on this scaffold hence became possible.     

An efficient synthesis of highly functionalized chiral lactams

A new method was developed to synthesize highly functionalized lactams via a one pot reductive amination/lactam formation reaction. This methodology is amenable for parallel synthesis and was used to prepare a large number of lactam analogs in a library format with good ee (de) retention.     

Synthesis Of 1-Benzazepines as Precursors of 1-Benzazepinediones

The synthesis of 6-hydroxy-7-nitro-1-benzazepine-2-one 7 from 5-hydroxy-1-tetralone 1 and 6-hydroxy-1-benzazepine-2-one 2 is described. Bromination of 6-hydroxy-1-benzazepine-2-one 2 with NBS in ethyl acetate afforded 7-bromo-6-hydroxy-1-benzazepine-2-one 13 and 7,9-dibromo-6-hydroxy-1-benzazepine-2-one 14. Oxidation of benzazepinone 13 with (diacetoxyiodo)benzene provided 7-bromo-1-benzazepine-2,6,9-trione 5.     

饶丹宁甲叉基取代左氧氟沙星衍生物的合成与抗肿瘤活性

为寻找提高氟喹诺酮肿瘤活的有效结构修饰策略,左氧氟沙星(3)的衍生物(S)-(-)-9-氟-2,3-二氢-3-甲基-10-(4-甲基-1-哌嗪基)-[1,4]噁嗪并[2,3,4-ij]-喹啉-7(4H)-酮-6-甲醛(5)与饶丹宁类(2a-2l)通过Claisen-Schmid缩合反应构建了饶丹宁甲叉基取代左氧氟沙星衍...     

Synthesis of C8-glycomimetics as potential glycosidases inhibitors

The synthesis of C8-glycomimetics is described from C₂-symmetrical polyhydroxylated cyclooctenes derived from carbocyclisation of enantiomerically pure 1,9-dienes by ring closing metathesis. Their obtention notably involved either hydroboration followed by oxidation to carbasugars or to cyclooctanones then reductive amination, or formation of a cis-cyclic sulfate followed by successive introduction of an azido group, reduction and subsequent reductive amination. The biological activity of the C8-carbasugars and related aminocyclitols, analogous to voglibose, has been evaluated towards several commercially available glycosidases.     

Synthesis of functionalized porphyrins as oxygen ligand receptors

Oxophilic synthetic receptors were designed and synthesized using a porphyrin scaffold, with the aim of constructing a preorganized complementary binding site for phenols and carbohydrates. We pursued three strategies for phenol recognition: (1) Lewis acid/Lewis base combinations serving as a hydrogen bond donor and acceptor for the OH group, (2) Lewis base/pi-pi stacking, targeting both the OH group and the aromatic moiety of phenols, and (3) exchange of the axial hydroxyl ligand on a trivalent and oxophilic metal center of aluminum porphyrin. For the recognition of acidic phenols, the most promising recognition motif was Lewis base/pi-pi stacking, which can bind to phenols with a hydrogen bond and pi-pi stacking interactions. [5-(8-Quinolyl)-10,15,20-triphenylporphyrinato]zinc binds to p-nitrophenol with a binding constant of 540 M(-)(1) in CHCl(3) at 25 degrees C. For carbohydrate recognition, we designed the metalloporphyrin receptor having 8-quinolyl groups and o-carbomethoxymethoxyphenyl groups, where these Lewis basic parts serve as the cooperative hydrogen bonding sites for the hydroxyl groups of glucoside. The receptor binds to beta-octyl glucoside with a binding constant of 7.35 x 10(4) M(-)(1) in CHCl(3) at 15 degrees C, demonstrating importance of formation of a highly ordered hydrogen bonding network between the receptor and the guest. These binding features have significant implications for the rational design of oxophilic artificial receptors.     

Synthesis of functionalized carboranes as potential anticancer and BNCT agents

Carboranyl aldehydes react with alpha,beta-unsaturated esters, ketones, and nitriles in the presence of DABCO to provide functionalized carboranyl alcohols in good yields. Acetates of these alcohols undergo a facile isomerization with a variety of nucleophiles and afford structurally interesting carboranes. Biological evaluation of these molecules exhibited impressive antiproliferative activity for brain and breast cancer cells.     

Palladium(0)-catalyzed amination of allylic natural terpenic functionalized olefins

The palladium(0) catalyzed amination of allylic acetates and carbonates derivatives from terpenic olefins was carried out under mild conditions. The reaction offers a very good method for the preparation of allylic amines and thus to provide a useful entry to new functionalized terpenic olefin products. The mechanism involving a formation of p-allyl-palladium intermediate complex is in good agreement with the results obtained with the optically active substrates, as well as via an analysis of the observed regio-and stereoselectivity.      

Synthesis and characterization of functionalized silica as fillers of polymeric systems

This study investigates the functionalization of sol-gel silica with selected organic species, and compares the materials obtained to a commercially available silica functionalized under comparable conditions. Anilines with different active groups were grafted onto the surface of the silicas, via reaction with key surface sites, to modulate the hydrophobicity of the materials. The properties of the functionalized materials, as determined by FT-IR, DTA-TGA and nitrogen adsorption (surface area, S_BET) are discussed.     

Synthesis of C3-Symmetric star-shaped molecules containing 1,3-azoles via hetero-aryl Heck coupling

We have demonstrated a useful synthetic strategy to assemble star-shaped C₃-symmetric molecules containing 1,3-azole moieties at the periphery. To generate these C₃-symmetric heterocycles, we have employed the Pd/Cu-based coupling reactions. To this end, we have used benzoxazole, benzothiazole, and benzimidazole as coupling partners to generate the corresponding hetero-aryl Heck coupling products.     

Synthesis and characterization of functionalized amphiphilic polymers for utilization as surfactants

Eight novel PEG-based amphiphilic block copolymers having self-assembling properties has been reported in the present study. The polymers have been synthesized by reacting Poly(ethylene glycols) (PEGs) of different molecular weights viz. 600, 1000, 1500 and 2000 and dimethyl-5-hydroxyisophthalate in presence of concentrated H₂SO₄ as catalyst in solventless condition at 80–90°C and further alkylating the resulting polymers by attaching octyl and hexadecanyl chains to phenolic hydroxyl group. The resulting functionalized amphiphilic polymers have been characterized by ¹H and ¹³C-NMR spectroscopy. These polymers, when dissolved in water, aggregate to form micelles, giving sizes ranging from 13.00 to 87.24 nm as determined by Dynamic Light Scattering (DLS) instrument. The molecular weights have been also calculated from the DLS and are in the range 3.5×10⁴ to 1.8×10⁶ KDa (Kilo Daltons). Critical Micelle Concentrations (CMC) of the synthesized polymers was determined using electrical conductivity meter with values in the range of 105 to 138 mg L^?1 (milligrams per litre).     

Synthesis of 2-aminoazulene derivatives. Nucleophilic and palladium-catalyzed amination of 2-substituted azulene

Amination of 2-substituted azulene was carefully examined using several types of amines, and the scope and limitation of substrates and reagents in these direct nucleophilic aminations were found. The synthesis of 2-aminoazulenes was successfully achieved by the reaction of 2-bromoazulene with several amines via palladium-catalyzed amination.     

Malononitrile as a carbonyl synthon: a one-pot preparation of heteroaryl amide via a SNAr-oxidation-displacement strategy

Malononitrile could be utilized as a synthon for the carbonyl moiety via a one-pot process that was initiated via base-mediated S_NAr substitution of a heteroaryl halide. Subsequent peracetic acid oxidation of the resultant anion delivered an electrophilic acyl nitrile in situ that readily reacted with added nucleophiles to afford heteroaryl carboxylic acid derivatives. The reaction of the sodium salt of malononitrile with a series of heteroaryl chlorides followed by the subsequent addition of an amine and peracetic acid provided the corresponding heteroaryl amides.     

Diastereoselective synthesis of highly functionalized tetrahydroxanthenols--unprecedented access to privileged structural motifs

Tetrahydroxanthenones, which can be easily prepared by a domino oxa-Michael aldol condensation, offer various possibilities for diastereoselective functionalization, giving access to the stereocontrolled synthesis of stereochemical triades or tetrades, which represent privileged structural motifs. In most cases, the relative stereochemistry was unequivocally established by crystal structure analysis.