A short and efficient enantioselective route to a key intermediate for the total synthesis of forskolin

A simple route for the enantioselective synthesis of key intermediates (11 and 12) for the total synthesis of forskolin has been developed starting from acid 6 and (S)-alcohol 5. The latter is prepared by enantioselective catalytic CBS reduction of dienone 3, and is converted by an intramolecular Diels-Alder reaction to tricyclic lactone 9.     

Microwave-assisted "libraries from libraries" approach toward the synthesis of allyl- and C-cyclopropylalkylamides

Cascade reactions of internal and terminal alkynes, zirconocene hydrochloride, dimethylzinc, and phosphinoyl imines (prepared in one step from aldehydes and diphenylphosphinoyl amide) lead to allylic phosphinoyl amides after aqueous workup. Microwave acceleration allows the completion of this one-pot reaction sequence in 10 min. These allylic amides can be converted into a variety of derivatives, including carbamates and sulfonamides, or reacted prior to workup with diiodomethane to give novel C-cyclopropylalkylamides. A solution-phase "libraries from libraries" approach was used to generate an intermediate 20-member library which was subsequently expanded to a 100-member library by a series of N-functionalizations. The biological activity was evaluated in an assay for competitive binding to the estrogen receptor (ERalpha), revealing three potent lead compounds of a new structural type.     

Examination of vanadium contaminated pillared rectorite catalysts with the atomic force microscope

When vanadyl naphthanate solutions in toluene are used to V-contaminate rectorite pillared with alumina clusters, V migration from the pillared clay microporous structure to the outer surface occurs during the thermal treatments used in catalyst preparation. The presence of V on the clay catalyst surface can be inferred from atomic force microscopy (AFM) images showing a marked decrease in surface roughness resulting from the presence of vanadia. AFM images show what are believed to be islands as well as stacks of vanadia layers on the clay surface. Irrespective of the thermal and hydrothermal treatments used to prepare these catalysts, atomic scale details of V-contaminated clay samples retain the surface parameters characteristic of the silicate layers in smectites. These results suggest that V on the clay surface is present as V=O groups attached to the three basal oxygens of the SiO₄ units that form the clay silicate layers. These VO units form an hexagonal arrangement of white spots having next neighbor (d_c) and lateral distance (d_l) of 5.2 Å and 9.1 Å, respectively.     

Synthesis of 6,7-disubstituted-5H-pyrrolo[2,3-b]pyrazines via palladium-catalyzed heteroannulation

A concise and efficient method for the preparation of 6,7-disubstituted-5H-pyrrolo[2,3-b]pyrazines via a palladium-catalyzed heteroannulation is reported. Both conventional and microwave heating were used to perform the reactions, with the latter showing dramatically improved results.     

A general stereocontrolled, convergent synthesis of oligoprenols that parallels the biosynthetic pathway

A solution is reported to the classic unsolved problem of stereoselective synthesis of all-E oligoprenols, such as E-farnesylfarnesol, by a cationic coupling analogous to the biosynthetic pathway. The simplicity and efficacy of the method, which is outlined in Scheme 1, are demonstrated by the synthesis of a series of all-E oligoprenols from C(20) to C(35) in uniformly excellent overall yield. The success of the approach is due not only to the highly E-stereoselective C-C coupling that forms the oligoprenyl chain but also to the development of efficient syntheses of allylic secondary silanes and E-oligoprenal acetals, and to a selective allylic demethoxylation reaction.     

Synthesis of di-t-alkylamines

Di-$\text{t}$-alkylamines can be synthesized efficiently by a three-step process: (1) oxidation of a $\text{t}$-alkylamine to a $\text{t}$-alkylnitroso compound with peracetic acid in ethyl acetate (2) conversion of the $\text{t}$-alkylnitroso compound to a tri-$\text{t}$-alkylhydroxylamine by successive trapping of two $\text{t}$-butyl radicals and (3) sodium naphthalide reduction to the di-$\text{t}$-alkylamine.     

Generation of peptide radical dications via low-energy collision-induced dissociation of [Cu<Superscript>II</Superscript>(terpy)(M + H)]<Superscript>·3+</Superscript>

The first example of the formation of hydrogen-deficient radical cations of the type [M + H](.2+) is demonstrated to occur through a one-electron-transfer mechanism upon low-energy collision-induced dissociation (CID) of gas-phase triply charged [Cu(II)(terpy)(M + H)](.3+) complex ions (where M is an angiotensin III or enkephalin derivative; terpy = 2,2':6',2'-terpyridine). The collision-induced dissociation of doubly charged [M + H](.2+) radical cations generates similar product ions to those prepared through hot electron capture dissociation (HECD). Isomeric isoleucine and leucine residues were distinguished by observing the mass differences between [z(n) + H](.+) and w(n)(+) ions (having the same residue number, n) of the Xle residues. The product ion spectrum of [z(n) + H](.+) reveals that the w(n)(+) ions are formed possibly from consecutive fragmentations of [z(n) + H](.+) ions. Although only the first few [M + H](.2+) species have been observed using this approach, these hydrogen-deficient radical cations produce fragment ions that have more structure-informative patterns and are very different from those formed during the low-energy tandem mass spectrometry of protonated peptides.     

Functionalized nanoparticles for liquid atmospheric pressure matrix-assisted laser desorption/ionization peptide analysis

Nanoparticles for the extraction of peptides and subsequent analysis using atmospheric pressure matrix-assisted laser desorption/ionization (APMALDI) have been evaluated. The atmospheric pressure source allows for particles to be directly introduced in the liquid matrix, minimizing sample loss and analysis time. Described in this work are two sample preparation procedures for liquid APMALDI analysis: a C18 functionalized silica nanoparticle for hydrophobic extractions, and an aptamer functionalized magnetite core nanoparticle for rapid, affinity extractions. The C18 particles provide a non-selective support for rapid profiling applications, while the aptamer particles are directed towards reducing the complexity in biological samples. The aptamer functionalized particles provide a more selective analyte-nanoparticle interaction whereby the tertiary structure of the analyte becomes more critical to the extraction. In both cases, the liquid APMALDI matrix provides a support for ionization, and acts as the releasing agent for the analyte-particle interaction. Additionally, analyte enrichment was possible due to the large surface-to-volume ratio of the particles. The experiments conducted with functionalized nanoparticles, in an atmospheric pressure liquid matrix, present a basis for further methodologies and utilities of silica nanoparticles to be developed.     

6-Substituted-5H-pyrrolo[2,3-b]pyrazines via palladium-catalyzed heteroannulation from N-(3-chloropyrazin-2-yl)-methanesulfonamide and alkynes

We herein report the efficient and convenient synthesis of 6-substituted-5H-pyrrolo[2,3-b]pyrazines. The reaction is a palladium-catalyzed heteroannulation process followed by deprotection to yield the desired pyrrolo[2,3-b]pyrazine substrates. The reaction starts with readily accessible N-(3-chloropyrazin-2-yl)-methanesulfonamide and commercially available terminal alkynes and works with aryl- and alkylalkynes.