Mariko Aso

Synthesis of Nitroxyl Radicals for Overhauser-enhanced Magnetic Resonance Imaging

Non‐invasive measurement and visualization of free radicals in vivo would be important to clarify their roles in the pathogenesis of free radical‐associated diseases. Nitroxyl radicals can react with free radicals and be derivatized to achieve specific cellular / subcellular localizing capabilities while retaining the simple spectral features useful in imaging. Overhauser‐enhanced magnetic resonance imaging (OMRI), which is a double resonance technique, creates images of free radical distributions in small animals by enhancing the water proton signal intensity via the Overhauser Effect. In this study, we synthesized various nitroxyl probes having 15N nuclei and deuterium, and measured the enhancement factor for Overhauser‐enhanced magnetic resonance imaging experiments. 15N‐D‐4‐Oxo‐2,2,6,6‐tetramethylpiperidine‐1‐oxyl (15N‐D‐oxo‐TEMPO) has the highest enhancement factor compared with other nitroxyl probes. The proton signal enhancement was higher for 15N‐labeled nitroxyl probes when compared to the 14N‐labeled analogues because of the reduced spectral multiplicity of the I = 1/2 nucleus. Furthermore, this enhancement is proportional to the line width and number of electron spin resonance lines of nitroxyl radicals. Finally, we compared the Overhauser‐enhanced magnetic resonance image of 15N‐labeled, deuterated 4‐Oxo‐2,2,6,6‐tetramethylpiperidine‐1‐oxyl with that of 14N‐H‐TEMPOL. These results suggested that the selective deuteration of the nitroxyl probes enhanced the signal‐to‐noise ratio and thereby improved spatial and temporal resolutions.

Preparation of optically active (R)- and (S)-allene-1,3-dicarboxylates and their asymmetric cycloaddition reactions with cyclopentadiene

Abstract Optically active ( R )- and ( S )- allene-1,3-dicarboxylates were prepared, and their asymmetric Diels-Alder reactions with cyclopentadiene in the presence of Lewis acid proceeded to afford the endo -adducts in high yields.

Synthesis of optically active 9-oxabicyclo[3.3.1]nona-2,6-diene as a cycloocta-1,5-diene equivalent and the corresponding tetrol

Abstract Highly enantio- and diastereo-selective synthesis of C2-symmetric 9-oxabicyclo[3.3.1]nona-2,6-diene and the corresponding C2-symmetric 2,3,6,7-tetrol has been achieved starting from optically active 5-cyclooctene-1,2-diol prepared by an enzymatic procedure.

Furannulation strategy. An efficient synthesis of fused 3-methylfurans

A two-step synthesis of fused 3-methylfurans (furannulation) by the addition of enolate anion of cyclic 1,3-dicarbonyl compounds to allenic sulfonium salt is described

Water-proton relaxivities of DNA oligomers carrying TEMPO radicals

5‐Uridine derivative carrying a TEMPO radical (UST) was prepared and its single strand (ssUST) and a double strand (dsUST) with its complementary strand were obtained. Similarly, single strands carrying two and five radicals (ssUST2 and ssUST5, respectively) and the corresponding double strands (dsUST2 and dsUST5) were prepared. Their electron paramagnetic resonance (EPR) spectra showed typical anisotropic broadening in the high field line. The rotational correlation times, τR, estimated by analyzing the EPR spectra are 1.1 × 10−10, 5.9 × 10−10, and 14 × 10−10 s for UST, ssUSTm, and dsUSTm, respectively. The water‐proton relaxivities, r1 and r2, at 25 MHz, 0.59 T, and 25 °C, also increased in the same order and the r1 values were 0.26, 0.41, and 0.56 mM−1 s−1 for UST, ssUSTm, and dsUSTm, respectively. The r1 values of 1.00 and 2.06 mM−1 s−1 for dsUST2 and dsUST5, respectively, were obtained. Copyright

Introduction of a quaternary stereogenic center to oxindole using cholinesterase-catalyzed asymmetric hydrolysis

Abstract Prochiral diesters bearing an oxindole skeleton were efficiently prepared from oxindole. Cholinesterase-catalyzed hydrolysis of prochiral dipropionate afforded an optically active monoalcohol of 95% e.e. The obtained monoalcohol might find use as a versatile intermediate in the enantioselective synthesis of indole alkaloids.

Asymmetric spirocyclization: A new type of acid-catalyzed intramolecular 1, 4-addition to form carba-spirocyclic compounds

Abstract Novel spirocyclization based on intramolecular 1, 4-addition and its asymmetric version have been developed using a combination of Lewis acid and 1, 2-diol. Treatment of five- and six-membered α, β-unsaturated cyclic ketones having a 4-oxopentyl group at the β-position with Lewis acid and ethylene glycol gave spiro[4.5]decane-2, 7-dione and spiro[5.5]undecane-2, 8-dione, respectively. The asymmetric version of this reaction has been developed by using optically active 1, 2-diol such as cyclohexane-1, 2-diol to afford the spirocyclic products of up to 85% e.e. Download : Download full-size image

Regioselective synthesis of maturone via Lewis acid catalyzed Diels-Alder reaction

Total synthesis of maturone (1) by the regioselective Diels-Alder reaction of benzofuranquinone (7) is described. Compound (7) was easily obtained by an application of the fused furan constructing method using allenic sulfonium salt (3) and cyclic 1,3-dicarbonyl compound

Asymmetric synthesis of C2-symmetric 5,6-bis(benzyloxy)cyclohexa-1,3-diene and a tricarbonyliron complex

The C2-symmetric 5,6-bis(benzyloxy)cyclohexa-1,3-diene and the corresponding tricarbonyliron complex have been synthesized in enantiomerically pure form. Reaction of the complex with trialkylaluminium gave a mono-alkylated product accompanied by racemization.

Synthesis of a new class of spin-labeled purine ribonucleosides and development of a novel nucleophilic reaction to form 2,6,8-trifunctionalized purine derivatives

Novel purine ribonucleosides with a tert-butylhydroxyamino function at the C8-position of the purine nucleus were synthesized, and were oxidized to aminoxyl radicals by treatment with Ag2O; after O-acylation of the tert-butylhydroxyamino group, nucleophilic substitution at the C2-position of the purine nucleus easily proceeded with elimination of the N-acyloxy group to provide a novel method for preparing C2-functionalized purine ribonucleosides.