Synthesis and Biological Evaluation of (2-Hydroxyethyl) 2-Deoxy-α-D-Threo-Pyranoside 3,4,2′-Trisphosphate,A Mimic of the Second Messenger Inositol 1,4,5-Trisphosphate

ABSTRACT

(2-Hydroxyethyl) 2-deoxy-α-D-threo-pentopyranoside 3,4,2′-trisphosphate (3) has been prepared starting from allyl-α-D-xylopyranoside. The suitably protected 2-deoxy intermediate obtained by judicious selective protection and deprotection has been phosphorylated using the phosphoramidite methodology. Final deprotection gave the expected analogue of myo-inositol 1,4,5-trisphosphate.     

Synthesis and Hepatic Metabolism of Xanthobilirubinic Acid Regioisomers

Summary.  A set of four regioisomeric dipyrrinone propionic acids has been synthesized and their hepatic metabolism examined in rats: xanthobilirubinic acid and pseudo-xanthobilirubinic acid each with a propionic acid on a pyrrole ring; exo-ψ-xanthobilirubinic acid and endo-ψ-xanthobilirubinic acid, each with a propionic acid transposed to a lactam ring. After intravenous injection all four isomers were excreted to some degree in unchanged form in bile in normal rats. Xanthobilirubinic acid, the structurally closest dipyrrinone to bilirubin, and exo-ψ-xanthobilirubinic acid were excreted almost entirely in unchanged form. However, a small fraction of xanthobilirubinic acid acyl glucuronide was also detected. More extensive acyl glucuronidation was observed for pseudo-xanthobilirubinic acid, and endo-ψ-xanthobilirubinic acid underwent slow metabolism to unidentified more polar products that did not seem to be glucuronides.     

Highly stereocontrolled synthesis of gem-difluoromethylenated azasugars: D- and L-1,4,6-trideoxy-4,4-difluoronojirimycin

[reaction: see text]. D-1,4,6-trideoxy-4,4-difluoronojirimycin and L-1,4,6-trideoxy-4,4-difluoronojirimycin, a novel series of gem-4,4-difluoromethylenated azasugars, were synthesized from CF3CH2OH in 10 steps. A key step was the highly diastereoselective construction of the piperidine ring via reductive amination.     

Synthesis of 1,4,6-Trideoxy-1,4-imino-D-mannitol: a potent α-mannosidase inhibitor

The title trihydroxypyrrolidine 4, readily synthesized $\text{in one step}$ from the naturally occurring sugar D-perosamine, is ten times more active than swainsonine as a competitive inhibitor of jackbean α-mannosidase.     

Synthesis and Evaluation of the Tetracyclic Ring-System of Isocryptolepine and Regioisomers for Antimalarial,Antiproliferative and Antimicrobial Activities

A series of novel quinoline-based tetracyclic ring-systems were synthesized and evaluated in vitro for their antiplasmodial, antiproliferative and antimicrobial activities. The novel hydroiodide salts 10 and 21 showed the most promising antiplasmodial inhibition, with compound 10 displaying higher selectivity than the employed standards. The antiproliferative assay revealed novel pyridophenanthridine 4b to be significantly more active against human prostate cancer (IC₅₀ = 24 nM) than Puromycin (IC₅₀ = 270 nM) and Doxorubicin (IC₅₀ = 830 nM), which are used for clinical treatment. Pyridocarbazoles 9 was also moderately effective against all the employed cancer cell lines and moreover showed excellent biofilm inhibition (9a: MBIC = 100 µM; 9b: MBIC = 100 µM).     

Synthesis of Novel Polyphosphate Analogues of Inositol 1,4,5-Trisphosphate

Abstract

The synthesis of novel polyphosphate mimics of inositol 1,4,5-trisphosphate, including ring-contracted and conformationally restricted analogues is reported.     

Design and Synthesis of a Potential Dopamine D-1 Antagonist

The diastereoselective synthesis of (±)-trans-transoid-7-bromo-8-hydroxy-1-methyl-1,2,3,4,4a,5,10,10a-octahydro-10-phenylbenzo[g]quinoline ( 8 ) is described, using an intramolecular Diels-Alder reaction and a reductive cyclisation for piperidine ring-formation as key steps. Compound 8 was prepared as a putative D-1 receptor antagonist which contains (2,2-diphenylethyl)amine as a partial structure.     

Synthesis of 1,4,6-tri-O-benzyl myo-inositol-A key intermediate to myo-inositol-1,2,5-O-trisphosphate

A new synthetic approach to 1,4,6-tri-O-benzyl myo-inositol was described on the basis of the regioselective benzylation of 1,2-O-isopropylidene-4,6-di-O-benzyl myo-inositol, subsequent acid hydrolysis, phosphorylation with tetrabenazylpyrophosphate and appropriate deprotec-tion.     

Synthesis and stereoselective glycosylation of D- and L-glycero-beta-D-manno-heptopyranoses

[reaction: see text] A method for the direct stereocontrolled synthesis of D- and L-glycero-beta-D-manno-heptopyranosides such as those found in the repeating unit of the O-specific polysaccharide from the CNCTC 113/92 LPS (serotype 54) is described. The method relies on the presence of a 4,6-O-benzylidene acetal to effect stereocontrol at the anomeric center; the configuration at C6 (L- or D-glycero) is of minimal importance.     

Synthesis of Pyrene‐based Planar Conjugated Polymers and the Regioisomers by Intramolecular Cyclization

Several planar conjugated polymers and model compounds containing pyrene units are synthesized. The precursor polymers and model compounds are obtained through the Pd(0)‐catalyzed Suzuki reaction, then the planar structure is formed through intramolecular cyclization in the presence of acid. We investigate the regioisomers in intramolecular cyclization reaction by using model compounds, suggesting that the syn‐ and anti‐structures are formed in ladder‐type polymer LP1 , and the syn‐structure is more easily formed in LP3 . The planar conjugated polymers and model compounds show untypical features of ladder‐type polymers, they display broad absorption and blue or blue‐green emission in solution, and interchain π‐π stacking in film still occurs. Moreover, the new polymers and model compounds are characterized by nuclear magnetic resonance (NMR) spectroscopy, gel‐permeation chromatography (GPC) and cyclic voltammetry (CV).     

Synthesis and polymerization of 2-butyl-7-methylene-1,4,6-trioxaspiro(4,4)nonane

2-Butyl-7-methylene-1,4,6-trioxaspiro(4,4)nonane ( 7 ) was prepared by the reaction of 2-(bromomethyl)-5-oxo-tetrahydrofuran with 1,2-epoxyhexane, followed by dehydrobromination. Compound 7 could be polymerized by free radical initiators to give a viscous polymer. The IR and NMR spectra of the polymers indicated that the polymer structure contained ester and ketone units in the backbone, and a cyclic acetal side chain. Compound 7 readily copolymerized with acrylonitrile in the presence and absence of radical initiators, but did not copolymerize well with styrene. Ultraviolet spectra suggest that the spontaneous polymerization proceeds via a chargetransfer complex between 7 as an electron donor and AN as an electron acceptor.     

Synthesis of D- and L-5-Oxaproline and of a New Captopril Analogue

The 1,3-dipolar cycloaddition of the C-t-butyloxycarbonyl-N -mannosyl-nitrone 5 , formed in situ from the partially protected D -mannose-oxime 3 and the glyoxylate 4 , to ethylene gave preferentially the (3S)-N-glycosyl-isoxazolidine 6 which was transformed into the 3-isoxazolidine-carboxylate (L -5-oxaproline ester) 12 and into some derivatives thereof. The (S)-configuration of 12 was proved by chemical correlation with a derivative of L -asparagine. The D -5-oxaproline ester was obtained from the corresponding N-ribosyl-nitrone 24 . Two protected dipeptides containing either C-terminal- ( 28 ) or N-terminal-5-oxaproline (= Opro) ( 30 ) were synthesized. Starting from 12 , the analogue 1 of captopril® ( 2 ) was prepared and its activity as an inhibitor of the angiotensin-converting-enzyme (ACE) was examined.     

2，3－二苯基－1，4，6－三氮杂二环[3.3.1]－2－壬烯单盐酸盐的合成及晶体结构

在ZrOCl_2的存在下,二乙烯三氨与联苯甲酰在甲醇中回流得到2,3－二苯基 －1,4,6－三氮杂二环[3.3.1]－2－壬烯单盐酸盐。对其进行了~1H NMR,IR和 UV-vis谱表征及X射线单晶衍射结构分析。晶体属单斜晶系,P2_1/c空间群,晶胞 参数为：a=1.69341(6)nm,b=0.77564(3)nm,c=1.21000(4)nm,β=96.1880(10)° ,Z=4,D_c=1.319g·cm~(-3)。该化合物是一非平面型具有部分不饱和键的氮杂桥 二环化合物,两个六元环中,与苯环连接的六元环为半椅式构型,另一六元环为椅 式构型。     

Synthesis and computational prediction of biological activity of 5-(nitrophenyl)-1,4,6-oxadithiocanes

5-(Nitrophenyl)-1,4,6-oxadithiocanes have been obtained by the reaction of p- and m-nitrobenzaldehydes with 2,2’-oxydiethanethiol in the presence of trimethylchlorosilane. The structure of the products has been proved by IR, NMR, and mass spectra.     

Synthesis of 1-azaspiro[2.4]hepta-1,4,6-trienes and azaspiroconjugation studied by photoelectron spectroscopy

1-Azaspiro[2.4]hepta-1,4,6-trienes 3a-c have been prepared by photolysis or thermolysis of 6-azidofulvenes 5a-c, which were accessible by nucleophilic substitution reactions of the precursors 4a,b or by nucleophilic addition of hydrazoic acid to ethenylidene-cyclopentadiene (6c). The UV photoelectron spectrum of 2-methyl-1-azaspiro[2.4]hepta-1,4,6-triene (3c) has been recorded and analyzed by making use of density functional theory (DFT) B3LYP calculations. Substantial homoconjugative interactions have been determined. The lone-pair orbital n(N) of the 2H-azirine nitrogen atom interacts with the pi 1 orbital of the cyclopentadiene ring. The energies of these orbitals are lowered or increased by 0.95 or 0.91 eV with respect to the two parent compounds cyclopentadiene (7) and 3-methyl-2H-azirine (9), respectively. In addition, in compound 3c the pi (C=N) orbital of the three-membered ring interacts with a sigma orbital of the cyclopentadiene unit and is destabilized by 0.47 eV by this effect.