Synthetic studies toward human interleukin-5

Disulfide-reduced form of IL-5 is assembled from three peptide segments in the N to C direction. Reconstitution of the protein under different folding conditions has also been investigated.     

Synthetic studies toward the bryostatins: a substrate-controlled approach to the A-ring

[reaction: see text] The synthesis of a C1-C13 A-ring subunit of bryostatin 1 is detailed. The key features of the approach include the convergent fragment assembly with a highly stereoselective construction of the C7-C8 bond indicated above.     

Asymmetric vinylogous Mannich reactions: a versatile approach to functionalized heterocycles

Asymmetric vinylogous Mannich reaction (VMR) of 2-(tert-butyldimethylsilyloxy)furan (TBSOF, 1) with (R(S))- or (S(S))-t-BS-imines (3) furnished 5-aminoalkylbutenolides 7a-k in 75-87% yields with anti/syn ratios ranging from 75:25 to 97:3. Butenolides 7a-f,k were readily converted into substituted lactones 8 and 5 and 6-substituted 5-hydroxypiperidin-2-ones 11a-g, which are, in turn, key intermediates for the synthesis of many bioactive compounds.     

Synthetic studies toward the zoanthamine alkaloids: synthesis of the fully functionalized BC ring motif

A synthetic approach toward lactone 20, representing the fully functionalized BC ring motif of the zoanthamine alkaloids, has been developed and is presented herein. The challenging C9 quaternary center of 20 was installed by a Wilkinson hydrogenation of enone 17 followed by construction of an α-bromo acetal and intramolecular cyclization exclusively from the α face of the BC ring system.     

Pyrazolinofullerenes: a less known type of highly versatile fullerene derivatives

The cycloaddition of readily available nitrile imines to [60]fullerene affording 2-pyrazolino[60]fullerenes is a versatile procedure for the functionalization of fullerenes. In contrast to other functionalization methods these cycloadducts are obtained generally in good yields as single isomers, thus avoiding the formation of undesired stereoisomers. This tutorial review discusses these less known fullerene compounds that display, however, interesting electrochemical and photophysical properties. Owing to their outstanding electron acceptor character, similar to pristine C(60), and their remarkable thermal stability, these cycloadducts are good candidates for incorporation in photovoltaic devices. However, more work is needed in order to design better pyrazolinofullerenes exhibiting improved performances for PV applications.     

Synthesis studies directed toward gelsemine. A new synthesis of highly functionalized cis-hydroisoquinolines

Cis-Hydroisoquinolines can be prepared in good yields by treatment of readily available endo-1-(cyanomethyl)-6-hydroxybicyclo [2.2.2]oct-5-en-1-yl amines with KH as summarized in Scheme 3.     

Development of a [3+3] cycloaddition strategy toward functionalized piperidines

This paper describes a novel route to functionalized piperidines via a formal [3+3] cycloaddition reaction of activated aziridines and palladium-trimethylenemethane (Pd-TMM) complexes. The cycloaddition reaction generally proceeds enantiospecifically with ring opening at the least hindered site of the aziridine. Therefore, readily available enantiomerically pure 2-substituted aziridines can be utilized to prepare enantiomerically pure 2-substituted piperidines in good to excellent yield. The N-substituent on the aziridine proved to be crucial to the success of this reaction with only 4-toluenesulfonyl (Ts) and 4-methoxybenzenesulfonyl (PMBS) aziridines permitting smooth cycloaddition to take place. Additionally, spirocyclic aziridines have been found to participate in the [3+3] cycloaddition reaction, whereas 2,3-disubstituted aziridines can be applied to provide fused bicyclic piperidines, albeit in low yield.     

Synthetic studies directed toward the pseurotins. Part II. Synthesis of related highly functionalized furan-3(2H)-ones

The synthesis of 2,2-bis(hydroxymethyl)-4-methyl-5-phenylfuran-3(2H)-one ( 9 ), 5-[(1S,2S,Z)-1,2-(ethylidenedioxy)hex-3-enyl]-2,2-bis(hydroxymethyl)-4-methylfuran-3(2H)-one ( 24 ), and 5-[(1S,2S,Z)-1,2-(ethylidenedioxy)hex-3-enyl]-2-(hydroxymethyl)-4-methylfuran-3(2H)-one ( 28 ), which represent more advanced, suitably functionalized intermediates for the synthesis of pseurotin A ( 1 ), a secondary metabolite of Pseudeurotium ovalis STOLK , is described.     

Alkylated sugar amino acids: a new entry toward highly functionalized dipeptide isosters

[reaction: see text] Novel highly functionalized dipeptide isosters are synthesized via a diastereoselective alkyl/arylation protocol of a glucose-derived (R)-tert-butanesulfinylimine. One of these novel sugar amino acid derivatives, a D-Ala-Ser/Thr isostere, was applied in a peptide synthesis protocol to afford a cyclic tetramer.     

Synthetic studies toward longeracemine: The intramolecular [4+2] cycloaddition of 3H-pyrroles

Model studies to develop a tetracyclization approach mimicking the proposed biosynthesis of the secodaphnane-type alkaloid longeracemine are described. These studies have culminated in the successful implementation of a 3H-pyrrole [4+2] cycloaddition that delivers a longeracemine-like azabicycle containing three contiguous quaternary stereocenters.     

Aziridinofullerene: a versatile platform for functionalized fullerenes

An aziridine moiety on the fullerene core can serve as an acid-triggered reacting template for the controlled synthesis of a range of functionalized fullerenes that are otherwise difficult to synthesize in an efficient and selective manner. A copper-catalyzed aziridination of C(60) for the practical synthesis of aziridinofullerene 1 and acid-catalyzed reactions of 1 with mono- and bifunctional nucleophiles as well as alkynes are described. The rapid generation of structural diversity in a single chemical operation using the common platform 1 is notable.     

Synthetic studies toward diazonamide A. A novel approach for polyoxazole synthesis

[Reaction in text]The indole-bisoxazole fragment of diazonamide A was prepared by a Chan-type rearrangement of a tertiary amide. This approach represents a remarkably direct strategy for polyoxazole synthesis.     

Tosylated glycerol carbonate, a versatile bis-electrophile to access new functionalized glycidol derivatives

The reactivity of tosylated glycerol carbonate 2 toward nucleophiles has been exploited to generate glycidol analogues protected with carbonate or carbamate groups. The activated glycerol 2 is a reasonable linking agent with thiol and alcohol nucleophiles and an excellent and selective one with primary amines, allowing efficient bis-functionalizations of glycerol.     

One-pot two-component [3 + 2] cycloaddition/annulation protocol for the synthesis of highly functionalized thiophene derivatives

An efficient and experimentally rapid protocol for the synthesis of hitherto unreported 2,3-dicarboalkoxy-4-aroyl/heteroaroyl/alkanoyl thiophenes has been developed via 1-2 (C-S) and 3-4 (C-C) bond connections promoted by 4-dimethylaminopyridine (DMAP). Optimally, the reaction takes only 3-5 min when β-oxodithioester and dialkyl acetylenedicarboxylate are stirred in DCM at room temperature in the presence of DMAP. This method allows a clean and general synthesis of previously inaccessible and synthetically demanding thiophenes containing the ferrocenyl group. The speed, experimental ease, and high yields of this process are improvements over existing methods to access this important substructure.     

Electrophoretically deposited L-cysteine functionalized MoS2@MWCNT nanocomposite platform: a smart approach toward highly sensitive and label-free detection of gentamicin

The exploitation of antibiotics has caused many side effects on the agriculture, environment, and human health. The existing methods have numerous shortcomings in determining gentamicin (GEN), a broad-spectrum antibiotic that causes nephrotoxicity and ototoxicity when found in excess. Here, an immunosensing platform to detect GEN using multiwalled carbon nanotubes (MWCNTs) and molybdenum disulfide (MoS₂) nanocomposite, deposited electrophoretically on indium tin oxide (ITO) glass has been developed. A novel 2-D graphene analog MoS₂@ MWCNTs nanocomposite was made via a facile and low-cost hydrothermal technique using l-cysteine to achieve remarkable electrochemical properties. Subsequently, a highly sensitive electrochemical immunosensor was fabricated by assembling monoclonal antibodies against gentamicin (anti-GEN) on a MoS₂@MWCNTs modified ITO electrode. The hetero-nanostructure formed on the immunosensor surface appeared relatively good conductor for accelerating the electron transfer. GEN was determined on anti-GEN modified electrodes by utilizing the differential pulse voltammetry technique by measuring the difference in current owing to the transfer of electrons directly between the redox species and immunoelectrodes. Under optimal experimental conditions, the fabricated immunosensor had a wide linear detection range of 1 × 10^?6–40 μg/mL, a high sensitivity of 13.55 μA (log μg/mL)^?1 and a low limit of detection and limit of quantification of 0.039 μg/mL and 0.130 μg/mL, respectively. The developed immunosensor also exhibits high reproducibility, repeatability, and good selectivity against various interferences. This electrochemical immunosensor having MoS₂ modified MWCNTs displays the excellent potential for the point-of-care device for GEN testing.     

Efficient entry to highly functionalized beta-lactams by regio- and stereoselective 1,3-dipolar cycloaddition reaction of 2-azetidinone-tethered nitrones. Synthetic applications

Racemic as well as optically pure 2-azetidinone-tethered nitrones, both cyclic and acyclic, were smoothly prepared from 4-oxoazetidine-2-carbaldehydes. The regio- and diastereoselectivities of the intermolecular 1,3-dipolar cycloaddition reactions of 2-azetidinone-tethered nitrones with substituted alkenes and alkynes were investigated. 2-Azetidinone-tethered nitrones on reacting with various dipolarophiles yielded isoxazolinyl-, isoxazolidinyl-, or fused polycyclic-beta-lactams, exhibiting good regio- and facial stereoselectivity in the most of the cases. In addition, some interesting transformations of these cycloadducts were performed, yielding aziridinyl beta-lactams or functionalized beta-alkoxycarbonyl gamma-lactams (derivatives of the aza analogue of paraconic acid).     

Synthesis of highly functionalized pyrrolidines via a mild one-pot, three-component 1,3-dipolar cycloaddition process

[reaction: see text] A simple and efficient one-pot, three-component synthesis of highly functionalized pyrrolidines via cascade imine --> azomethine ylide --> 1,3-dipolar cycloadditions is reported. Admixing a variety of aldehydes, dimethyl 2-aminomalonate, and electron deficient alkenes in THF leads to the clean production of pyrrolidines in good to excellent yields. The mild reaction conditions enabled the generation of previously inaccessible azomethine ylides from enolizable aldehydes. Endo selectivity was exclusive with N-phenyl maleimide and maleic anhydride. Good chemo-, regio-, and stereoselectivities were observed with methyl acrylate, though catalysis by Ag(I) was necessary with this dipolarophile.