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Biomedical subjects

Kevin D Moeller

Publications and source records attributed to Kevin D Moeller.

16 recordsLinked to original sources
PubMed2006

Building addressable libraries: The use of a mass spectrometry cleavable linker for monitoring reactions on a microelectrode array.

Time-of-flight secondary ion mass spectrometry (TOF SIMS) has been used in conjunction with a mass spectrometry cleavable linker to determine the percent conversion of reactions that were conducted site-selectively on an addressable microelectrode array. When combined with fluorescence techniques for analysis of the reactions, the TOF SIMS experiment provides a means for optimization of both reaction confinement and reaction efficiency on the microelectrode arrays.

Calibration↗
PubMed2006

Building functionalized peptidomimetics: use of electroauxiliaries for introducing N-acyliminium ions into peptides.

A series of silyl-substituted amino acids have been synthesized, inserted into peptides, and then employed as precursors for oxidatively generating reactive N-acyliminium ions. Both electrochemical and chemical oxidation procedures have been employed. N-Acyliminium ion generation in a solid-phase substrate as well as application to a small library of functionalized dipeptides has been demonstrated. Limitations in terms of how electron-rich the silyl groups can be as well as the compatibility of multiple silyl groups within a longer peptide are defined.

Acylation↗
PubMed2006

Building addressable libraries: site selective coumarin synthesis and the "real-time" signaling of antibody-coumarin binding.

[reaction: see text] The feasibility of using active semiconductor chips containing addressable arrays of microelectrodes for the "real-time" monitoring of biologically relevant binding events has been demonstrated by detecting the binding of a coumarin substrate by an anticoumarin antibody. The coumarin substrate was synthesized proximal to predetermined electrodes on the chip with the use of a Pd(II) reagent that was itself generated by using the selected electrodes. Once the coumarin was synthesized, its binding to the anticoumarin antibody was detected by monitoring the current associated with a ferrocene-ferrocinium ion redox cycle that was established between the electrodes on the chip and a remote auxiliary electrode.

Antibodies↗
PubMed2006

Building addressable libraries: spatially isolated, chip-based reductive amination reactions.

A Pd(II) reagent has been generated at preselected sites on an electrochemically addressable chip and used to effect the oxidation of the neighboring alcohols on the polymer coating the chip's surface. The resulting carbonyls were then used to accomplish site-selective reductive amination reactions on the chips. The work demonstrates that the confinement strategy developed for spatially isolated Wacker oxidations to specific sites on the chips is general and can be used for other Pd(II)-based reactions.

Alcohols↗
PubMed2005

Electrochemically assisted Heck reactions.

[reaction: see text] During efforts to develop chip-based Heck reaction chemistry, it was discovered that normal solution-phase Heck reactions can be dramatically accelerated using electrochemistry. The acceleration makes room temperature Heck reactions proceed at synthetically useful rates in the absence of added ligand. Presumably, the current passed through the reaction maintains a high level of active catalyst.

Benzene Derivatives↗
PubMed2005

Oxidative cyclization reactions: amide trapping groups and the synthesis of furanones.

Intramolecular anodic coupling reactions involving ketene dithioacetal radical cations and amide trapping groups have been examined. The reactions generate furanone products and benefit greatly from the addition of water to the reaction medium. The cyclization reactions lead to products having stereochemistry that is directly analogous to oxidative cyclization reactions utilizing ketene dithioiacetal radical cations and alcohol trapping groups. [reaction: see text]

Amides↗
PubMed2005

Building addressable libraries: the use of electrochemistry for spatially isolating a heck reaction on a chip.

Pd(0) was generated at preselected sites on an electrochemically addressable chip and then utilized to effect a Heck reaction. The Pd(0) was confined to the preselected electrodes with the use of allylmethyl carbonate. Unlike most mediated electrochemical reactions, the electrolysis in this case was not used to convert a stoichiometric process into a catalytic one by recycling the metal. Instead, the unique environment of the chip was used to interfere with a catalytic process to make it stoichiometric. This was done to gain spatial control over the reaction. The development of a strategy for conducting Pd(0)-catalyzed reactions on the chips should greatly expand the synthetic chemistry available for building chip-based libraries.

Combinatorial Chemistry Techniques↗
PubMed2004

Anodic coupling reactions: the use of N,O-ketene acetal coupling partners.

Intramolecular anodic olefin coupling reactions utilizing N,O-ketene acetals have been studied. Coupling reactions with both enol ether and allylsilane terminating groups were examined. The reactions involving the coupling of the N,O-ketene acetals with allylsilane groups were found to be much more efficient than corresponding reactions utilizing dithioketene acetal groups and allylsilanes. The reactions were also more efficient than the intramolecular coupling reactions between enol ethers and allylsilanes studied earlier.

Acetals↗
PubMed2004

Oxidative cyclizations: the asymmetric synthesis of (-)-alliacol A.

A tandem anodic coupling-Friedel-Crafts alkylation strategy has been used to rapidly complete the asymmetric synthesis of alliacol A. The anodic oxidation reaction allowed for the generation of a new bond between two nucleophiles. In the synthesis, the absolute stereochemistry of the final natural product is set relative to a methyl group that is incorporated early in the sequence using an asymmetric Michael reaction.

Agaricales↗
PubMed2004

Building addressable libraries: the use of electrochemistry for generating reactive Pd(II) reagents at preselected sites on a chip.

A Pd(II) reagent has been generated at preselected sites on an electrochemically addressable chip. The reagent was used to effect the Wacker oxidation of an olefin substrate bound to the chip near the electrode. The use of ethyl vinyl ether in the solution above the chip effectively kept the Pd(II) reagent generated at the preselected electrode from migrating to neighboring electrodes and initiating Wacker oxidations at unwanted sites on the chip.

2,4-Dinitrophenol↗
PubMed2003

Building functionalized peptidomimetics: new electroauxiliaries and the use of a chemical oxidant for introducing N-acyliminium ions into peptides.

[reaction: see text] The removal of electroauxiliaries from peptide substrates with chemical oxidants has been examined as a method for inserting N-acyliminium ions into the peptides. To this end, it was found that both 4-methoxyphenyldimethylsilyl and 2,4-dimethoxyphenyldimethylsilyl electroauxiliaries were readily cleaved with the use of ceric ammonium nitrate. Of the two groups, the 2,4-dimethoxyphenyldimethylsilyl electroauxiliary was the most labile under the oxidative conditions. The oxidation reactions were shown to be compatible with the use of a solid-phase substrate.

Acylation↗
PubMed2003

Anodic cyclization reactions: the total synthesis of alliacol a.

An anodic cyclization-Friedel Crafts alkylation strategy has been used to rapidly assemble the core ring system of alliacol A and to complete a formal total synthesis of the natural product. The anodic cyclization reaction was used to effect the coupling of a nucleophilic furan ring to the normally nucleophilic carbon of a silyl enol ether. The substrate for this initial cyclization reaction contained all of the carbons needed for completing the total synthesis. The electrolysis proceeded in high yield and could be accomplished with the use of a 6 V lantern battery.

Anions↗
PubMed2002

Oxidative cyclization based on reversing the polarity of enol ethers and ketene dithioacetals. Construction of a tetrahydrofuran ring and application to the synthesis of (+)-nemorensic Acid.

The utility of oxidative cyclization reactions for the construction of tetrahydrofuran rings has been examined. In these experiments, alcohol nucleophiles were found to be effective traps for radical cation intermediates generated from both enol ether and ketene dithioacetal groups. The reactivity of the alcohol trapping group appeared to lie between that of an enol ether and an allylsilane trapping group. The stereochemical outcome of cyclization reactions originating from the oxidation of an enol ether was found to be controlled by stereoelectronic factors. The utility of these cyclization reactions was illustrated with the synthesis of a key tetrahydrofuran building block for the synthesis of linalool oxide and rotundisine. Cyclization reactions triggered by the oxidation of a ketene dithioacetal led to far greater levels of stereoselectivity. The stereochemical outcome of these reactions was shown to arise from steric factors involving the larger ketene acetal group. The synthetic utility of cyclizations utilizing ketene dithioacetal derived radical cations was demonstrated by completing an asymmetric synthesis of (+)-nemorensic acid. Finally, the reactions were shown to be compatible with the use of an amide nucleophile and the direct formation of a lactone product.

Acetals↗
PubMed2002

Anodic cyclization reactions: capitalizing on an intramolecular electron transfer to trigger the synthesis of a key tetrahydropyran building block.

An anodic cyclization reaction between an enol ether radical cation and an oxygen nucleophile has been used to make a tetrahydropyran building block for the C(10)-C(16) portion of bryostatin. The oxidative cyclization was successful despite the presence of a thioacetal group that has a lower oxidation potential than the enol ether. Experimental evidence suggested that the reaction proceeded through an initial oxidation of the thioacetal followed by an intramolecular electron transfer to form the enol ether radical cation that was subsequently trapped by the oxygen nucleophile. The formation of the desired cyclic product could be explained using the Curtin-Hammett principle. By taking advantage of the intramolecular electron-transfer reaction, we used the presence of a thioacetal in an electrolysis substrate to selectively oxidize a proximal enol ether in the presence of an otherwise identical but more remote enol ether.

Electrodes↗
PubMed2002

Conformationally restricted TRH analogues: constraining the pyroglutamate region.

A modified synthetic route has been developed so that the steric size of constraints added to the pyroglutamate region of TRH (pGluHisProNH(2)) can be varied. Both an analogue with a smaller ethylene bridge and a larger, more flexible propane bridge in this region have been synthesized. These analogues were synthesized in order to probe why the initial incorporation of an ethane bridge into this region of the molecule had led to an analogue with a binding constant and potency three times lower than that of an directly analogous unconstrained analogue. The data for both analogues indicated that the fall off in activity caused by the ethane bridge in the initial analogue was not caused by the size of the bridge.

Biochemistry↗