Divergent Synthesis of All Possible Optically Active Regioisomers of Myo‐Inositol Mono‐ and Bisphosphates

All possible optically active regioisomers of myo‐inositol mono‐ and bisphosphates were synthesized using inositol derivatives suitably protected with various protecting groups (IR_ns) as key intermediates. A series of procedures including Novozym 435 catalyzed enzymatic resolution of (3aR,4S,7S,7aR)‐rel‐3a,4,7,7a‐tetrahydro‐2,2‐dimethyl‐1,3‐benzodioxole‐4,7‐diol diacetate, several protection and deprotection reactions, and acyl migration afforded two enantiomeric pairs of IR₅ and six enantiomeric pairs of IR₄. Phosphorylation of these key intermediates by the phosphitylation and oxidation procedure gave the target products after removal of the protecting groups.      

Studies on the Synthesis and Antiproliferative Activities of 13‐cis‐Retinoyl Sugar Derivatives

New retinoyl sugar derivatives of 13‐cis‐retinoic acid were synthesized in three ways in this paper in order to enhance pharmacal effects, especially antiproliferative activities of 13‐cis‐retinoic acid. Their structures were confirmed by IR, ¹H‐NMR, ¹³C‐NMR, and MS spectra and their antiproliferative activities were determined in vitro using human cancer lines. Results showed that some compounds possessed potential antitumor activities.     

Thiosugar Nucleosides. Effect of Sulfur in the Synthesis of Substituted Azido‐5‐Thio‐D‐Gluco‐ and Allopyranosyl‐N‐Nucleosides and New Isothionucleoside Derivatives Thereof

1‐(2,3,4‐tri‐O‐acety‐6‐azido‐6‐deoxy‐5‐thio‐β‐D‐glucopyranosyl)thymine 5 and the 6‐thio‐septanosylthymine analogue 7 were obtained via the intramolecular displacement of the corresponding tosylate 2 by azide. Alternatively, 5 was obtained from bromination of alcohol 1 in the presence of azide. Deblocking of 5 afforded the nucleoside 6. Glycosylation of the tetraacetate 11, obtained by acetolysis of 10 with thymine, afforded the 3‐O‐tosyl‐β‐D‐glucopyranosylthymine derivative 13, which furnished the 3‐azido‐3‐deoxy‐β‐D‐allopyranosyl‐thymine analogue 14 on reaction with azide ion. Alternatively, the glucoside 12 gave the corresponding gluco analogue 16 on treatment with azide. Acetolysis of 16 furnished the tetraacetate 17, which was subjected for glycosylation to give the gluco nucleoside 18. Deblocking of 14 and 18 afforded the free 3‐azido‐nucleosides 15 and 19, respectively. The isothionucleoside 21 was prepared from treatment of thymine with the 2,3‐epoxide derivative 20 in the presence of Ti(i‐PrO)₄ and triethyl amine. Mild acid hydrolysis of 21 afforded 22. Cycloaddition of the 2‐azido‐altroside 23 with dimethyl acetylenedicarboxylate gave the 1,2,3‐triazole derivative 24. Treatment of 24 with methanolic ammonia afforded the 4,5‐carboxamide analogue 25. The conformations of the new products were studied by NMR spectroscopy.     

Efficient and Simple Synthesis of Substituted 3‐Phenyl‐7‐methoxybenzopyrans as Pseudo‐Vitamin‐D3 Analogs

An efficient and simple synthesis of substituted 3‐phenyl‐7‐methoxybenzopyrans as pseudo‐vitamin‐D₃ analogs in good yields under mild reaction conditions is described.     

Improved Synthesis of 1‐Benzenesulfinyl Piperidine and Analogs for the Activation of Thioglycosides in Conjunction with Trifluoromethanesulfonic Anhydride*

An improved protocol for the large‐scale production of 1‐benzenesulfinyl piperidine and other sulfinamides is described. It is demonstrated that 1‐benzenesulfinyl pyrrolidine and N,N‐diethyl benzenesulfinamide function analogously to 1‐benzenesulfinyl piperidine in the trifluoromethanesulfonic anhydride‐mediated activation of thioglycosides, and that their less crystalline nature enables them to be used at ?78°C as opposed to the ?60°C required to keep 1‐benzenesulfinyl piperidine in solution. N,N-Dicyclohexyl benzenesulfinamide does not activate thioglycosides in combination with trifluoromethanesulfonic anhydride, which is attributed to its greater steric bulk.     

Synthesis and Biological Evaluation of New 4‐Deacety‐1,7,9‐trideoxy‐10‐oxopaclitaxel via Sinenxan A

A new 4‐deacety‐1,7,9‐trideoxy‐10‐oxopaclitaxel (compound 1) was prepared in 21 steps via sinenxan A, a biosynthetic taxane. The biological evaluation in vitro against human cancer lines showed compound 1 to be devoid of cytotoxicity.     

Synthesis and Antiviral Evaluation of Some 5‐N‐Arylaminomethyl‐2‐glycosylsulphanyl‐1,3,4‐oxadiazoles and Their Analogs against Hepatitis A and Herpes Simplex Viruses

N‐Arylaminomethyl‐3H‐1,3,4‐oxadiazole‐2‐thiones 2a,b were prepared from the corresponding N‐arylglycinoylhydrazides. A number of their thioglycoside derivatives 4–7a–c and S‐functionalized analogs 8–11a,b were synthesized by the reaction with different acetobromosugars and acyclic hydroxyalkylating agents. The antiviral activity of a number of the synthesized compounds against herpes simplex virus type 1 (HSV‐1) and hepatitis A virus (HAV) was evaluated. Compounds 5a and 5b showed promising results against HAV.     

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 Characterization of the First Pyrrolidine‐Based Chiral Ionic Liquids

The first example of pyrrolidine‐based room‐temperature chiral ionic liquids using 2‐aminobutanol as chiral auxiliary is described.     

Synthesis of Different 3,5‐Diazidofuranoses: A New and General Synthesis Pathway

Diamino‐ and diazidofuranoses represent useful precursors, for example, for the synthesis of substituted nucleosides and metal complexes, respectively. Known procedures for their synthesis lack the availability of cheap starting materials, adequate yields, and the access to all possible diastereomeres. Therefore, 3,5‐diazido‐3,5‐dideoxy‐ and ‐2,3,5‐trideoxyfuranoses both with ribo‐ and xylo‐configuration were prepared using different approaches.     

New Approach for the Synthesis of N‐Indolyl Ketones and Aldehydes

A new approach for the synthesis of N‐indolyl ketones and aldehydes was developed. In the reaction of N‐indolyl carboxylic acids with alkyl lithium, an interesting phenomenon appeared when using THF as solvent instead of ethyl ether.     

Versatile Sugar Derivatives for the Synthesis of Potential Degradable Hydrophilic‐Hydrophobic Polyurethanes and Polyureas

Biodegradable polymers obtained from renewable natural sources are currently receiving increasing attention because they are an alternative to the traditional petroleum‐based plastics. In the present communication we describe the synthesis of the diol monomers 2,3,4‐tri‐O‐benzyl‐L‐arabinitol (ABnOH) and 2,3,4‐tri‐O‐benzylxylitol (XBnOH), and the diamino monomers 1,5‐diamino‐1,5‐dideoxy‐2,3,4‐tri‐O‐benzyl‐L‐arabinitol (ABnNH ₂ ) and 1,5‐diamino‐1,5‐dideoxy‐2,3,4‐tri‐O‐benzylxylitol (XBnNH ₂ ), which can be used in the preparation of new potentially biodegradable sugar‐based polymers. As an example, we describe the synthesis and characterization of a polyurethane [PU‐(ABnOH‐HMDI)] and a polyurea [PUR‐(ABnNH₂‐HMDI)] by poly addition reaction of ABnOH and ABnNH ₂ with 1,6‐hexamethylene diisocyanate.      

Synthesis and Characterization of Polyimide‐Silica Hybrids: Effect of Matrix Polarity on the Mechanical and Thermal Properties

Polyimide‐silica hybrid materials have been prepared through the sol‐gel process by mixing various proportions of tetraethoxysilane (TEOS) with polyamic acids (PAAs). Two types of PPAs were employed. The first was obtained by reacting an equimolar mixture of oxydianiline (ODA) and pyromellitic dianhydride (PMDA) in dimethylactamide (DMAc) as solvent. The second was prepared using a mixture of ODA and 2,2‐Bis(3‐amino‐4‐hydroxyphenyl)hexafluoropropane (6F‐OHDA) in molar ratio 9:1, respectively and reacting with a stoichiometric amount of PMDA in DMAc. Polyamic acids were converted to polyimides and a sol‐gel reaction proceeded simultaneously by heating the hybrid films to 300°C. The hydroxyl groups from 6F‐OHDA allows the secondary bonding between the polyimide and growing silica phase and thus retard the gross phase separation. Only the 10 mol% addition of 6F‐OHDA in the polyimide chain resulted in a drastically different microstructure for the resulting hybrids. SEM, stress‐strain analysis, temperature variation of storage and loss modulus, and thermal stability were used to characterize the hybrid materials. Properties of both types of hybrids have been compared and related to the two different types of structures of polyimides used in the preparation of the hybrids.     

Synthesis and Evaluation of Substituted Pyrazoles: Potential Antimalarials Targeting the Enoyl‐ACP Reductase of Plasmodium Falciparum

A series of 1,5‐ and 1,3‐diarylsubstituted pyrazoles were designed, synthesized, and evaluated for their ability to inhibit enoyl‐ACP reductase of Plasmodium falciparum. The inhibitory activity of these synthesized compounds was evaluated in a continuous spectrophotometric assay. Of all the compounds analyzed, NAS‐81 and NAS‐39 inhibited the enzyme with IC₅₀ values of 30 µM and 50 µM, respectively. The mode of ligand binding was investigated by docking the synthetic inhibitors at the active site of the crystal structure of the enzyme.     

Alternative Synthesis of 1,2,3,4‐Tetramethoxy‐5‐methylbenzene: A Key Intermediate for Preparing Coenzyme Q Homologs and Analogs

Preparation of 1,2,3,4‐tetramethoxy‐5‐methylbenzene (1) through a new process from pyrogallol is described. In the preparation, a modified mild brominating agent was employed, and a simple introduction of methyl group into aromatic ring through chloromethylation of the corresponding substrate (4), followed by reductive dehalogenation, was achieved successfully with good yields.     

A New Ferrocene‐Containing Polyamide Prepared from an Improved Synthesis of 1,1′‐Ferrocene Dicarbonyl Chloride and Ferrocene‐Based Diamine

1,1′‐Ferrocene dicarbonyl chloride was prepared by an improved and efficient conversion method from 1,1′‐ferrocene dicarboxylic acid and reacted by esterification with p‐nitrophenol, followed by reduction, to form a ferrocene‐based diamine, 1,1′‐ferrocene bis (p‐amino phenylate). The diamine was characterized by elemental analysis, ¹H NMR, and Fourier transform infrared (FTIR) spectroscopy and subsequently condensed with 1,1′‐ferrocene dicarbonyl chloride to form a novel main chain ferrocene‐containing polyamide, poly{imino ferrocene bis (p‐amino phenylate) ferrocenyl}. Its polymeric nature was confirmed by its physical properties, elemental analysis, FTIR spectroscopy, differential scanning calorimetry, and thermogravimetric studies.     

A Novel,Convenient Synthesis of the 3‐O‐β‐D‐ and 4′‐O‐β‐D‐Glucopyranosides of trans‐Resveratrol

Abstract

trans‐Resveratrol‐3‐O‐β‐D‐glucupyranoside (trans‐piceid, 2) and trans‐resveratrol‐4′‐O‐β‐D‐glucupyranoside (trans‐resveratroloside 3) are the naturally occurring O‐glucoside conjugates of the polyphenolic stilbenoid trans‐resveratrol 1. Recently, attention has been drawn towards the interesting biological properties of the glucoside conjugates 2 and 3 as well as those of the aglycone 1. The fact that only limited quantities can be obtained by extraction from natural sources has prompted the development of novel syntheses of 2 and 3, based on a convergent Heck‐coupling strategy, which now conveniently allows for the preparation of multi‐milligram to gram quantities of each.     

Effect of Amino‐Acid‐Based Polar Oils on the Krafft Temperature and Solubilization in Ionic and Nonionic Surfactant Solutions

Abstract

The Krafft temperature and solubilization power of ionic and nonionic surfactants in aqueous solutions are strongly affected by added polar oils such as amino‐acid‐based oils (e.g., N‐acylamino acid esters, AAE), because they tend to be solubilized in the surfactant palisade layer. The Krafft temperatures of 5 wt.% sodium dodecyl sulfate (SDS)‐water and octaoxyethylene octadecyl ether (C₁₈EO₈)‐water systems largely decreases upon addition of AAE and 1‐hexanol, whereas it decreases very slightly in isopropyl myristate (IPM) and n‐dodecane. The lowering of the Krafft temperature can be explained by the same mechanism as the melting‐temperature reduction of mixing two ordinary substances. Namely, the polar oils are solubilized in the surfactant palisade layer of micelles and reduce the melting temperature of hydrated solid‐surfactant (Krafft temperature). On the other hand, non‐polar oil such as dodecane is solubilized deep inside micelles and makes an oil pool. The solubilization of non‐polar oil is enhanced by mixing surfactant with AAE due to an increase in micellar size.     

Synthesis and Characterization of New Unsaturated Polyesters Containing 4‐Phenylcyclohexanone Moiety in the Main Chain

Two series of new unsaturated polyesters were prepared from 2,6‐bis(p‐hydroxidebenzylidene)‐4‐phenylcyclohexanone (I) and 2,6‐divanillyidene‐4‐phenylcyclohexanone (II) with adipoyl, isophthaloyl, sebacoyl and terephthaloyl dichlorides utilizing the interfacial polycondensation technique at ambient temperature. In addition to that, the model compounds were synthesized by reacting (I) and (II) with benzoyl chloride. The model compound and polyester samples have been characterized by elemental and spectral analyses. The unsaturated polyesters have inherent viscosities of 0.96–1.63 dl/g. All the polyesters are amorphous and most of them are partially soluble in most common organic solvents, but easily soluble in concentrated sulfuric acid. Their glass transition temperatures (T_g) range from190.15 to 245.28°C, and the temperatures of 10% weight loss as high as 180 to 220°C in air, indicating that these aromatic polyesters have high T_g and excellent thermal stability.     

Organocatalytic Synthesis of Higher‐Carbon Sugars: Efficient Protocol for the Synthesis of Natural Sedoheptulose and d‐Glycero‐l‐galacto‐oct‐2‐ulose

Herein we report a short and efficient protocol for the synthesis of naturally occurring higher‐carbon sugars—sedoheptulose (d‐altro‐hept‐2‐ulose) and d‐glycero‐l‐galacto‐oct‐2‐ulose—from readily available sugar aldehydes and dihydroxyacetone (DHA). The key step includes a diastereoselective organocatalytic syn‐selective aldol reaction of DHA with d‐erythrose and d‐xylose, respectively. The methodology presented can be expanded to the synthesis of various higher sugars by means of syn‐selective carbon–carbon‐bond‐forming aldol reactions promoted by primary‐based organocatalysts. For example, this methodology provided useful access to d‐glycero‐d‐galacto‐oct‐2‐ulose and 1‐deoxy‐d‐glycero‐d‐galacto‐oct‐2‐ulose from d‐arabinose in high yield (85 and 74 %, respectively) and high stereoselectivity (99:1).