Cyclopropanation of Various Substrates via Simmons-Smith and Michael-Initiated Ring Closure (MIRC) Reactions

Cyclopropanation of various electron rich and electron deficient olefins via Simmons-Smith and Michael-initiated ring closure reactions was studied in our research. Cinnamyl alcohol 18 was succesfully cyclopropanated in a good to excellent yield using Simmons-Smith reactions. Methyl and benzyl crotonate 14 and 16 were labile in MIRC reaction condition indicated by the detection of starting material degradation in the NMR spectra of the crude reactions, and allowed a low to moderate product yield. The other starting materials, i.e., cinnamaldehyde 19, methyl cinnamate 20, mono- and di-protected cross-coupled product (4R,5R,E)-methyl 5-(tert-butyldimethylsilyloxy)-4-hydroxyhepta-2,6-dienoate 25 and (4R,5R,E)-methyl 5-(tert-butyldimethylsilyloxy)-4-(methoxymethoxy)hepta-2,6-dienoate 26, were apparently incompatible to the reaction condition set in our study

Synthesis of Indenes by a BF₃·OEt₂‑Mediated, One-Pot Reaction of Aryl Homopropargyl Alcohols, Aldehydes, and Arenes

A new and efficient protocol to prepare indenes is reported. Assisted by boron trifluoride diethyl etherate, the one-pot reaction of aryl homopropargyl alcohols and aldehydes in the presence of arenes yielded indene derivatives. The reaction was studied with various substrates, which suggests a cascade reaction including a sequence of Prins, Friedel–Crafts, ring-opening reactions, and Friedel–Crafts to form three C–C bonds leading to indenes

Anti-addition of Dimethylsulfoxonium Methylide to Acyclic α,β-Unsaturated Ketones and Its Application in Formal Synthesis of an Eicosanoid

Cyclopropanation using dimethylsulfoxonium methylide (Corey–Chaykovsky reaction) was examined with a series of linear α,β-unsaturated ketones, and the results showed that the major trajectory for the addition of the sulfur ylide to the enones is anti, related to the γ-substituent. The stereochemical assignment for the generated cyclopropanes was achieved by X-ray crystallography or comparing with the reported spectroscopic data. We found that the diastereoselectivity was influenced by several factors, including the protecting groups, solvents, and temperatures, and good anti/syn ratios (>10:1) were often obtained using the <i>tert</i>-butyldimethylsilyl and <i>tert</i>-butyldiphenylsilyl-protected substrates. The method was applied to a formal synthesis of a natural eicosanoid with good efficiency

Microwave-Assisted Direct Thioesterification of Carboxylic Acids

A one-pot synthesis of thioesters directly from carboxylic acids, <i>N,N</i>′-diphenylthiourea, triethylamine, and primary alkyl halides is described. Microwave-assisted heating and a catalytic amount of 4-(dimethylamino)­pyridine (DMAP) further improved the yields. Both aromatic and aliphatic carboxylic acids were converted to the corresponding thioesters, and many functional groups were compatible with this reaction. Several possible reaction intermediates were investigated, and the quaternary ammonium salts, derived from alkyl halides and tertiary amines, were the intermediates to yield thioesters. A new reaction mechanism for this thioesterification is proposed

Bortezomib Congeners Induce Apoptosis of Hepatocellular Carcinoma via CIP2A Inhibition

CIP2A is an oncoprotein that upregulates p-Akt and promotes cancer cell proliferation and survival. The proteasome inhibitor bortezomib has been shown to reduce CIP2A and lead to cell apoptosis. Here; we modified the functional group of bortezomib to generate a series of novel compounds and conducted a structure–activity relationship (SAR) study. The results showed that compound 1 was able to repress CIP2A expression and cell apoptosis in the same manner as bortezomib, but with less potency in inhibition of proteasome activity. This finding provides a new direction for the design of CIP2A inhibitors