RNA interference (RNAi) holds considerable promise as a therapeutic approach to silence disease-causing genes, particularly those that encode so-called 'non-druggable' targets that are not amenable to conventional therapeutics such as small molecules, proteins, or monoclonal antibodies. The main obstacle to achieving in vivo gene silencing by RNAi technologies is delivery. Here we show that chemically modified short interfering RNAs (siRNAs) can silence an endogenous gene encoding apolipoprotein B (apoB) after intravenous injection in mice. Administration of chemically modified siRNAs resulted in silencing of the apoB messenger RNA in liver and jejunum, decreased plasma levels of apoB protein, and reduced total cholesterol. We also show that these siRNAs can silence human apoB in a transgenic mouse model. In our in vivo study, the mechanism of action for the siRNAs was proven to occur through RNAi-mediated mRNA degradation, and we determined that cleavage of the apoB mRNA occurred specifically at the predicted site. These findings demonstrate the therapeutic potential of siRNAs for the treatment of disease.

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Under mild conditions (40 atm O(2), 28 degrees C, 10-15 h), an efficient aerobic oxidation of cycloalkanes to cycloalkanols can be achieved using nanostructured amorphous metals such as Fe and Co and an amorphous alloy like Fe(20)Ni(80) as catalysts. For example, cyclohexane is oxidized to cyclohexanol with 32-41 % conversion, while 1-adamantanol is formed from adamantane with 52-57 % conversion.

A new bifunctional squaramide organocatalyst derived from L-proline mediated the first enantioselective synthesis of dihydrospiro[indoline-3,4'-pyrano[2,3-c]pyrazole] derivatives in excellent enantioselectivity by reacting pyrazolones with isatylidine β,γ-unsaturated α-ketoester. This new catalyst outperformed widely used thioureas and squaramides in inducing enantioselectivity.

Quantitative oxidative conversion of thiols to disulfides was effected by aqueous 30% H 2 O 2 in trifluoroethanol at ambient temperature under neutral conditions. Selective oxidative conversion of thiols to disulfides is of interest from both a biological 1 and a synthetic point of view. 2 It was found that under biological conditions this reaction occurs in the presence of oxidants such as flavins, cytochromes and dehydroascorbic acid. 3 Thiols are among functional groups which can be easily over oxidized and therefore extensive studies have been carried out for their controlled oxidation. 4 Although hydrogen peroxide is known to oxidize some thiols to disulfides, 2a this requires very long reaction times and proceeds only in strong acidic or basic conditions. Reagents like iodine/hydrogen iodide, 5 bromine-aqueous potassium-hydrogencarbonate, 4c molecular bromine, 6 Sm/BiCl 3 in aqueous medium, 7 FeCl 3 /NaI 2b and KMnO 4 −CuSO 4 2c were reported in the literature to effect oxidative coupling of thiols to disulfides. Enzymatic 8 and electrochemical 9 methods are also known to perform this oxidative transformation. Most of the existing methods involve the use of metal catalysts or reagents like halogens and always suffer with effluents due to these reagents. So there is a need to develop a clean, mild and efficient methodology to synthesize aliphatic, aromatic and heteroaromatic disulfides.

Enantioselective synthesis of 2,3-dihydroquinazolinones (DHQZs) was accomplished using readily available Sc(III)-inda-pybox as the catalyst. This is the first report on the metal catalyzed asymmetric intramolecular amidation of imines to synthesize DHQZs.

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3-Allyl-3-hydroxyoxindoles were synthesized in very good enantio- (up to 97% ee) and diastereoselectivities (dr up to 7.6:1) with contiguous quaternary and tertiary stereogenic centers by employing tartrate derived bi(oxazoline) in Pd-catalyzed allylation of 3-OBoc-oxindole. Synthetic utility of 3-allyl-3-hydroxyoxindole was demonstrated by synthesizing a highly substituted spiro(oxindole-3,2'-tetrahydrofuran) derivative in good yield and stereoselectivity.