Letters in Organic Chemistry - Volume 6, Issue 4, 2009

Employing a flexible synthetic strategy towards laurenditerpenol, two analogues featuring the 7- oxabicyclo[2.2.1]heptane ring system present in the natural product have been prepared and their ability to inhibit HIF-1 activation has been evaluated. Their weak activity indicates the importance of the cyclohexenol part of the prototype.

Novel bone targeting naproxen prodrugs with poly(aspartic acid) moieties and with two and three poly(aspartic acid) sequences peptide dendrimers were synthesized using a conventional method. The modified naproxen conjugates were incubated with hydroxyapatite in PBS at physiological conditions over 16h. The study revealed the hydroxyapatite binding properties of poly(aspartic acid) and it was found that the peptide dendrimer prodrugs exhibited a faster initial binding and a greater total binding. The obtained binding data in vitro indicated that the peptide dendrimers with poly(aspartic acid) sequences were useful for the development of new bone targeting molecules for drug delivery to bone.

The synthesis of kigelinone thiophene analogs and related naphtho[2,3-b]thiophene-4,9-quinones from 2- substituted 4,7-dimethoxybenzo[b]thiophenes via an oxidative deprotection, Diels-Alder, and oxidative aromatization reaction sequence is reported. The 2-substituted naphtho[2,3-b]thiophene-4,9-quinones display significant antitumor activity in the range IC50 1.1-47 μM on a panel of four distinct human cancer cell lines.

Several 1,3,4-trisubstituted pyrazole derivatives were synthesized via condensation with the appropriate amine, sulphonamide, acid hydrazide, or benzyl thiosemicarbazide derivatives. The newly synthesized compounds were screened for a possible anti-inflammatory effect in a rat model of air-pouch carrageenan-induced inflammation. The results revealed that some of the newly synthesized compounds exhibited a significant anti-inflammatory effect in terms of reducing exudation and/or leukocytic accumulation at the site of inflammation. Thus, compared to carrageenan-induced inflammation group, compounds 3, 9, 13, and 17 were particularly associated with significant decrease in both the volume of exudate and leukocyte accumulation while compounds 4, 7, 10, 11 and 15 were associated with significant decrease in the volume of inflammatory exudate without a corresponding decrease in the number of accumulated leukocytes. Moreover, a docked pose of compound 17 was obtained and bound to cyclooxygenase active site of COX-2 using Molecular Operating Environment (MOE) module.

The first synthesis of lissoclimide-type alkaloids is described. Starting from commercial (+)-sclareolide, the aldehyde γ-bicyclohomofarnesal is synthesized and coupled, through an aldol reaction, with succinimide. The antitumor activity of several lissoclimide analogues is also reported.

A facile and mild synthesis of 4-tosyl-4,5-dihydrooxazoles is described. The reaction between tosyl methyl isocyanide (TosMIC) and cinnamic or aromatic aldehydes is catalyzed by triethylamine, affording trans-5-styryl- or 5-aryl-4- tosyl-4,5-dihydrooxazoles in quantitative yields without further purification. The mild reaction conditions allowed for the first time the use of cinnamaldehyde derivatives with excellent results.

The resolution of 1,1'-binaphthyl-2-yl(phenyl)methanone O-acetyl oxime catalyzed by lipase in three different ionic liquids, 1-butyl-3-methylimidazolium hexafluoride-phosphate, [bmim][PF6], 1-butyl-3-methylimidazolium tetrafluoroborate, [bmim][BF4] and N-butyl-pyridium hexafluorophosphate, [BuPy][PF6] and organic solvents was studied. The lipase shows low activity in ionic liquids and organic solvent with ionic liquids as the additive, while the lipase coated with ionic liquids gives the best enantioselectivity as high as 95 %.

The first organocatalytic approach to erythro and threo lactam derivatives was successfully achieved from the addition of TBSOP (1) to aromatic and aliphatic aldehydes in the presence of a commercially available urea-derivative 5 supporting the broad potential for hydrogen-bond catalysis in the vinylogous Mukaiyama aldol addition. The transition states leading to the major diastereoisomers are discussed.

A new kind of ketolides, bearing a pyrazolinyl moiety at C-12 position, was designed and firstly synthesized starting from clarithromycin via ten steps. The title compound was evaluated for its antibacterial activities against several pathogens in vitro, and was found with potent effects on both S. aureus (ATCC6538p) and S. epidermidis (ATCC12228). The structures of new compounds were elucidated by 1HNMR, 13CNMR, MS and HRMS.

p-tert-Butylcalix[6]arene was attempted to O-alkylate with alcohols and diols under the Mitsunobu protocol. Regio-and conformation-selective reactions were not observed with alcohols and oligoethylene glycols, but 1,6-hexaneand 1,8-octanediols effected cone-selective A,D-bridging. Exhaustive alkylation of the remaining four OH groups in a cyclized molecule was carried out under base-promoted conditions and the conformation of the products along with the metal ion binding properties were studied by NMR methods.

Bis(tetraethylammonium)bis(1,3-dithiole-2-thione-4,5-dithiolato) zincate (5), and 4,5-bis(cyanoethylthio)-1,3- dithiole-2-thione (6) were reacted with 6-deoxy-6-iodo-glucopyranose (2) and glucopyranosyl bromide (3) to synthesize DMIT-carbohydrate conjugates.

Treatment of thiols with a mixture of periodic acid/sodium hydrogen sulfite gave the corresponding disulfides in good yield.

A convenient method of synthesis of the optically active dialkyl diselenides from the pinane group is described. The 3-hydroxy and 3-alkoxy derivatives of bis(cis-myrtanyl) diselenide have been obtained. The influence of a structure of the resulting diselenides on the diastereomeric excess of the methoxyselenenylation reaction and the selenocyclization have been investigated.

The first example of salan-vanadium catalyzed enantioselective ring-opening of meso-epoxides has been reported, which furnished β-hydroxy sulfides in good yields and moderate enantioselectivities.

An ionic liquid mediated novel protocol for enantioselective epoxidation of α,β-unsaturated ketones employing hydrogen peroxide as an oxidant in the presence of phase transfer catalyst has been developed. The protocol is essentially mild, rapid and environmentally benign employing ambient temperature ionic liquids. The use of ionic liquids facilitates ease of product isolation and catalyst recovery.

Chemo and homoselective catalytic oxidation of sulfides has been developed. A variety of aliphatic and aromatic sulfides are subjected to the sulfoxidation reaction using ZrCl4, NaNO2 and catalytic amounts of KBr or NaBr in the presence of wet SiO2 (50 % w/w) in acetonitrile at room temperature.

The diastereomeric pairs a and b of novel 16-spiro-dioxaphosphorinanes 3-11 were synthesised via the phosphorylation of 16,16-bis(hydroxymethyl)estrone 3-methyl ether (1) and its 17β-hydroxy analogue (2) and their stereostructures were investigated by different NMR methods.

Reaction of polymer-supported selenium bromide with ortho allylated phenols and subsequent cleavage from the polymer by treatment of methyl iodide efficiently afforded 2-iodomethyl-2,3-dihydrobenzofurans in good yields and high purities. The polymeric reagent can be regenerated and reused as environmentally friendly reagent.

Amino acids and some of their derivatives are strong polar organic compounds. Non-deuterated formic acid was used as an inexpensive, convenient, and practical 13C NMR solvent for these strong polar compounds. It was also used to determine hydroxyl carboxylic acids and nucleosides. 13C NMR chemical shifts in formic acid of representative examples and widely used solvents in organic reactions were provided. Formic acid is a counterpart to commonly used perdeuterated chloroform, dimethyl sulfoxide, methanol, and water.