Complete synthesis of the bicyclic ring of a mutacin analog with orthogonally protected lanthionine via solid-phase intracyclization.

Mutacin 1140 (MU1140) is a naturally occurring lantibiotic derived from posttranslational modifications of a ribosomally synthesized peptide during the fermentation of a bacterium called Streptococcus mutans, the etiological agent of dental cavities. A practical approach for chemically synthesizing lantibiotics would be a valuable tool to expand the MU1140 library with additional semisynthetic analogs. In turn, an expanded library may prove useful to explore additional therapeutic indications for this pipeline of novel compounds.

Ionic liquids based on azolate anions.

Compartmentalized molecular level design of new energetic materials based on energetic azolate anions allows for the examination of the effects of both cation and anion on the physiochemical properties of ionic liquids. Thirty one novel salts were synthesized by pairing diverse cations (tetraphenylphosphonium, ethyltriphenylphosphonium, N-phenyl pyridinium, 1-butyl-3-methylimidazolium, tetramethyl-, tetraethyl-, and tetrabutylammonium) with azolate anions (5-nitrobenzimidazolate, 5-nitrobenzotriazolate, 3,5-dinitro-1,2,4-triazolate, 2,4-dinitroimidazolate, 4-nitro-1,2,3-triazolate, 4,5-dinitroimidazolate, 4,5-dicyanoimidazolate, 4-nitroimidazolate, and tetrazolate). These salts have been characterized by DSC, TGA, and single crystal X-ray crystallography.

Preparation of polyfunctional acyl azides.

A general synthesis of acyl azides from the corresponding N-acyl benzotriazoles is described. The procedure affords acyl azides in good yields and avoids the use of acid activators and NO+ equivalents typically employed to synthesize these compounds from acid chlorides and hydrazides, respectively.

Novel syntheses of chiral beta- and gamma-amino acid derivatives utilizing N-protected (aminoacyl)benzotriazoles from aspartic and glutamic acids.

Friedel-Crafts reactions of N-protected (alpha-aminoacyl)benzotriazoles with hetero- and benzenoid- aromatics give alpha-amino ketones that can be reduced by either triethyl silane or sodium borohydride to form the corresponding beta- and gamma-amino acid derivatives. The preservation of chirality throughout this process is confirmed by chiral HPLC results.

Combustible ionic liquids by design: is laboratory safety another ionic liquid myth?

The non-flammability of ionic liquids (ILs) is often highlighted as a safety advantage of ILs over volatile organic compounds (VOCs), but the fact that many ILs are not flammable themselves does not mean that they are safe to use near fire and/or heat sources; a large group of ILs (including commercially available ILs) are combustible due to the nature of their positive heats of formation, oxygen content, and decomposition products.

In search of ionic liquids incorporating azolate anions.

Twenty-eight novel salts with tetramethyl-, tetraethyl-, and tetrabutylammonium and 1-butyl-3-methylimidazolium cations paired with 3,5-dinitro-1,2,4-triazolate, 4-nitro-1,2,3-triazolate, 2,4-dinitroimidazolate, 4,5-dinitroimidazolate, 4,5-dicyanoimidazolate, 4-nitroimidazolate, and tetrazolate anions have been prepared and characterized by using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and single-crystal X-ray crystallography. The effects of cation and anion type and structure on the physicochemical properties of the resulting salts, including several ionic liquids, have been examined and discussed. Ionic liquids (defined as having m.

Synthesis of heteroaryl 1,2-diketones.

Reactions of lithiated heteroaryl- (or aryl-) methylbenzotriazoles 4a-e with heteroaryl (or aryl) esters 5a-f give alpha-benzotriazolyl ketones 6a-n in average yields of 90-95%. Oxidation of ketones 6a-l in aqueous DMSO in the presence of oxygen and sodium bicarbonate gave heteroaryl- (aryl-) 1,2-ethanediones 7a-l in average yields of 60-80%.

1-butyl-3-methylimidazolium 3,5-dinitro-1,2,4-triazolate: a novel ionic liquid containing a rigid, planar energetic anion.

The novel ionic liquid, 1-butyl-3-methylimidazolium 3,5-dinitro-1,2,4-triazolate has been synthesized and exhibits an unexpectedly low melting point (35 degrees C) considering the size and shape of the rigid, planar anion; analogous tetraalkylammonium salts (methyl, ethyl and n-butyl) have also been prepared and the tetraethylammonium example was characterized by single crystal X-ray diffraction.

A novel route to imidoylbenzotriazoles and their application for the synthesis of enaminones.

Reactions of secondary amides 2a-i with 1-chloro-1H-benzotriazole and triphenylphosphine give imidoylbenzotriazoles 3a-i. The treatment of 3a,b,e,g with silyl enol ethers 5a,b in the presence of potassium tert-butoxide provides a new general approach to enaminoketones 6a-h.

Benzotriazolyl-mediated 1,2-shifts of electron-rich heterocycles.

The anion formed from the lithiation of 1-[(methylthio)methyl]-1H-benzotriazole 1 with n-BuLi adds to heteroaryl ketones to give 2-benzotriazolyl alcohols 3a-m. Thermolysis of 3a-g in the presence of zinc bromide induces a 1,2-shift of heteroaromatic groups to form ketones 4a-g. By contrast, in the rearrangement of 2-benzotriazolyl alcohols 3h,i,k-m migration of the phenyl group rather than the corresponding heteroaromatic groups occurred to give ketones 4h,i,k-m.

General and efficient insertion of carbons carrying benzotriazole.

Anions formed from the lithiation of 1-(1-benzotriazolylalkyl)benzotriazoles (1, 6) and 1-(1-methylthioalkyl)benzotriazoles (10 and 10a) with n-BuLi underwent additions to cyclic and acyclic ketones giving intermediates 3a-f, 7b-f, and 11b-d, respectively, in excellent yields. Thermal rearrangements of intermediates 3a,b,d-f and 7b-d,f in the presence of zinc bromide provided one-carbon chain-extended or ring-expanded alpha-benzotriazolyl ketones 4a,b,d-f and 8b-d,f in moderate yields with excellent regioselectivity. By contrast, intermediates 11b-d on treatment with zinc bromide loose a molecule of benzotriazole followed by intramolecular cyclization of the resulting intermediates 12b-d to provide the 2,3- and 1,2,3-substituted indenes 13b-d in good yields.

Syntheses of Examples of the 5,6-dihydro-4H-[1,2,3]triazolo[4,5,1-ij]quinoline, 4,5,6,7-tetrahydro[1,2,3]triazolo[4,5,1-jk][1,4]benzodiazepine, and 5,6,7,8-tetrahydro-4H-[1,2,3]triazolo[4,5,1-kl][1]benzazocine ring systems.

Lithiation of 1-vinylbenzotriazole 9 with n-BuLi (2 equiv) generates dianion 10, which upon subsequent reaction with 1,2- and 1,4-diketones affords 14 and 13, representatives of the 5,6-dihydro-4H-[1,2,3]triazolo[4,5,1-ij]quinoline 1 and 5,6,7,8-tetrahydro-4H-[1,2,3]triazolo[4,5,1-kl][1]benzazocine 2 ring systems, respectively. Reactions of dianion 10 with isocyanates give 15a,b, which contain the 4,5,6,7-tetrahydro[1,2,3]triazolo[4,5,1-jk][1,4]benzodiazepine 3 ring system.

Convenient preparation of tert-butyl beta-(protected amino)esters.

Refluxing an aldehyde 1 with benzotriazole and benzylcarbamate in the presence of a catalytic amount of p-TsOH gave the corresponding benzyloxycarbonylamino-1-(1-benzotriazolyl)alkane 2 in good yields. Compounds 2 treated with substituted tert-butyl acetates 3 using LDA as a base afford smoothly and under mild conditions the N-2-protected 3-aminoalkanoic esters 4.