Synthesis and characterization of new low-cost ILs based on butylammonium cation and application to lignocellulose hydrolysis.

Fourteen ionic liquids (ILs) were obtained and characterized by nuclear magnetic resonance and infra-red spectroscopy. One of these liquids, n-butylammonium acetate, was used in the treatment of coir fiber prior to acid hydrolysis. For this purpose, the fiber was pulped with 8% (w/w) sodium hydroxide for 6h under 2.5 atm pressure at 137°C and then treated with IL for 2h at 90°C. The samples were hydrolyzed in acetic acid at different concentrations and temperatures. The reducing sugar concentrations were determined in all samples, and the optimal hydrolysis conditions were established (32.2% acetic acid at 122.4°C). The reaction time was also studied, and the conversion was maximized at 3h. Under the best hydrolysis conditions, crude fiber, pulping fiber, and IL-treated fiber were hydrolyzed to yield 8.53%, 47.58%, and 89.75% of reducing sugars, respectively.

Synthesis and biological evaluation of acyclic phosphonic acid nucleoside derivatives.

As part of a project to generate a library of nucleosides as potential antiviral agents, a small subset of novel acyclic phosphonic acid nucleosides was prepared. Practical synthetic routes are described for three targets, which were then tested against HIV, hepatitis C virus (HCV), and Dengue virus.

Identification of fused-ring alkanoic acids with improved pharmacokinetic profiles that act as G protein-coupled receptor 40/free fatty acid receptor 1 agonists.

The G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) has emerged as an attractive target for a novel insulin secretagogue with glucose dependency. We previously identified phenylpropanoic acid derivative 1 (3-{4-[(2',6'-dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl}propanoic acid) as a potent and orally available GPR40/FFA1 agonist; however, 1 exhibited high clearance and low oral bioavailability, which was likely due to its susceptibility to ß-oxidation at the phenylpropanoic acid moiety. To identify long-acting compounds, we attempted to block the metabolically labile sites at the phenylpropanoic acid moiety by introducing a fused-ring structure. Various fused-ring alkanoic acids with potent GPR40/FFA1 activities and good PK profiles were produced. Further optimizations of the lipophilic portion and the acidic moiety led to the discovery of dihydrobenzofuran derivative 53 ((6-{[4'-(2-ethoxyethoxy)-2',6'-dimethylbiphenyl-3-yl]methoxy}-2,3-dihydro-1-benzofuran-3-yl)acetic acid), which acted as a GPR40/FFA1 agonist with in vivo efficacy during an oral glucose tolerance test (OGTT) in rats with impaired glucose tolerance.

Synthesis and antiviral activity evaluation of acyclic 2'-azanucleosides bearing a phosphonomethoxy function in the side chain.

Acyclic 2'-azanucleosides with a phosphonomethoxy function in the side chain were obtained by coupling of diethyl {2-[N-(pivaloyloxymethyl)-N-(p-toluenesulfonyl)amino]ethoxymethyl}phosphonate with the pyrimidine nucleobases via the Vorbrüggen-type protocol. The compounds were evaluated in vitro for activity against a broad variety of RNA and DNA viruses.

A convergent route for the total synthesis of malyngamides O, P, Q, and R.

A convergent, enantioselective and general synthetic route to a class of marine natural products-malyngamides O (1), P (2), Q (3), R (4), 5''-epi-3 and 5''-epi-4-bearing a novel vinyl chloride structural motif was developed. The key steps involved construction of the vinyl chloride functionality by Wittig reaction, a DCC/HOBt-promoted amidation, an aldol reaction in the construction of the basic backbone of 1, 2, 3, 4, 5''-epi-3, and 5''-epi-4, and methylation of an enol moiety via either base/acid conditions or a Mitsunobu reaction. Moreover, the absolute configuration of the stereogenic center at C-5'' in 3 was further confirmed by synthesis of the natural product and its C-5'' epimer.

Short synthesis and antiviral activity of acyclic phosphonic acid nucleoside analogues.

An efficient route for synthesizing novel allylic and cyclopropanoid phosphonic acid nucleoside analogues is described. The condensation of the bromine derivatives 6 and 18 with nucleoside bases (A, U, T, C, G) under standard nucleophilic substitution and deprotection conditions, afforded the target phosphonic acid nucleoside analogues. These compounds were evaluated for their antiviral properties against various viruses. Cyclopropanoid phosphonic adenine nucleoside analogue 23 showed significant anti-HIV activity.

Synthesis of cyclic and acyclic beta-amino acids via chelation-controlled 1,3-dipolar cycloaddition.

Isoxazolidines have been synthesized in diastereomeric excess up to 94% via a MgBr2-induced chelation-controlled 1,3-dipolar cycloaddition reaction with N-hydroxyphenylglycinol as a chiral auxiliary. The diastereomerically pure isoxazolidines were further transformed into cyclic and acyclic beta-amino acid derivatives.

Lewis acid catalyzed intramolecular Diels-Alder reactions of acyclic (Z)-substituted 1,3-dienes.

Lewis acid catalyzed intramolecular Diels-Alder reactions of trienes (E,E,Z)-1a-d, (E,E,Z)-4a-d, and (E,Z,Z)-7a,b are described. Trienes containing enal or enone dienophiles cyclize in excellent yield under mild conditions using substoichiometric amounts of MeAlCl(2), in most cases with high levels of diastereoselectivity. The thermal IMDA reactions of 1a, 4a, and 7a require forcing conditions and proceed in low yield with reversed stereoselectivity in the cases of 1a and 4a.