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Here, we report the design and synthesis of isolable rotational isomers with a hexahydro-1,2,4,5-tetrazine core. The mechanism of the isomerization via a twist-boat conformation was elucidated by DFT calculations.

Chiral binaphthyldiimine-Ni(II)-catalyzed asymmetric 1,3-dipolar cycloaddition reactions between acyclic carbonyl ylides generated from donor-acceptor oxiranes and aldehydes are reported. Both aromatic and aliphatic aldehydes could be used as dipolarophiles, providing

Phosphonium ylide catalysis through an oxidative quenching cycle has been developed for visible-light-driven C−H imidation of arenes and heteroarenes. The present protocol could be applied not only to trihalomethylative lactonization reactions involving trifluoromethyl, trichloromethyl, and tribromomethyl radicals but also to the first example of an organophotoredox-catalyzed imidative lactonization reaction involving a nitrogen-centered electrophilic radical species.

Objective Among treatment options for coronavirus infectious disease 2019 (COVID-19), well-studied oral medications are limited. We conducted a multicenter non-randomized, uncontrolled single-arm prospective study to assess the efficacy and safety of favipiravir for patients with COVID-19. Methods One hundred participants were sequentially recruited to 2 cohorts: cohort 1 (Day 1: 1,600 mg/day, Day 2 to 14: 600 mg/day, n=50) and cohort 2 (Day 1: 1,800 mg/day, Day 2 to 14: 800 mg/day, n=50). The efficacy endpoint was the negative conversion rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the odds ratio (OR) of cohort 2 to cohort 1 for negative conversion on Day 10 was calculated. Characteristics of all participants and profiles of adverse events (AEs) were collected and analyzed. Results The mean age of participants was 62.8±17.6 years old. Thirty-four patients (34.0%) experienced worsening pneumonia, 7 (7.0%) were intubated, and 4 (4.0%) died during the observation period. Cohort 2 showed a higher negative conversion rate than cohort 1 [adjusted OR 3.32 (95% confidence interval (CI), 1.17 to 9.38), p=0.024], and this association was maintained after adjusting for the age, sex, body mass index, and baseline C-reactive protein level. Regarding adverse events, hyperuricemia was most frequently observed followed by an elevation of the liver enzyme levels (all-grade: 49.0%, Grade ≥3: 12.0%), and cohort 2 tended to have a higher incidence than cohort 1. However, no remarkable association of adverse events was observed between patients65 and ≥65 years old. Conclusion The antiviral efficacy of favipiravir was difficult to interpret due to the limitation of the study design. However, no remarkable issues with safety or tolerability associated with favipiravir were observed, even in elderly patients with COVID-19.

The base-promoted switchable synthesis of five- and six-membered cyclic carbamates using atmospheric pressure carbon dioxide as the C1 source was developed. The chemoselectivity of products was simply controlled by changing bases and solvents. The reaction proceeds effectively under mild conditions, affording valuable cyclic carbamates. Experimental results and DFT studies revealed the reaction mechanism.

The development of carbon dioxide fixation under mild conditions is a central theme in organic synthesis. Despite the tremendous progress in the field of organocatalysis in the past two decades, the coupling reactions of epoxides with carbon dioxide that proceed at atmospheric pressure at temperatures of less than 100 °C have remained challenging. In our aspirational studies of tetraarylphosphonium salts (TAPS) catalysis, we report here the bifunctional TAPS-catalyzed synthesis of five-membered cyclic carbonates by chemical fixation using 1 atm of carbon dioxide at 60 °C. Intriguing substituent effects of TAPS were observed, in which electron-donating groups enhanced their reactivity. In addition, the mechanism was thoroughly investigated by undertaking both experimental and theoretical studies, suggesting that the electronic properties of TAPS affect carbon dioxide insertion into halohydrin intermediates. The results provided fruitful information to understand the origin of the TAPS behavior, which would contribute to the design of novel catalysts for carbon dioxide capture.

Chiral Lewis acid-catalyzed asymmetric alcohol addition reactions to cyclic carbonyl ylides generated from N-(α-diazocarbonyl)-2-oxazolidinones featuring a dual catalytic system are reported. Construction of a chiral quaternary heteroatom-substituted carbon center was accomplished in which the unique heterobicycles were obtained in good yields with high stereoselection. The alcohol adducts were successfully converted to optically active oxazolidine-2,4-diones by hydrolysis. Mechanistic studies by DFT calculations revealed that alcohols could be activated by Lewis acids, enabling enantioselective protonation of the carbonyl ylides.

A phosphonium ylide-based visible light organophotoredox catalyst has been designed and successfully applied to halohydrin synthesis using trichloroacetonitrile and epoxides. An oxidative quenching cycle by the ylide catalyst was established, which was confirmed by experimental mechanistic studies.

The potential of carbonyl-stabilized phosphonium ylides as ligands for novel catalysis was explored. We found that the combination of phosphonium ylides and metal halide salts efficiently catalyzed the reaction of epoxides with carbon dioxide under mild conditions. Five-membered cyclic carbonates, including disubstituted cyclic carbonates, were obtained in good yields with the use of 1 atm of carbon dioxide at 35 °C. Terminal epoxides could be converted to

Preparation of 4-hydroxymethyl-substituted oxazolidinones including optically active ones, in which tetraarylphosphonium salts catalyze the reaction of glycidol with isocyanates effectively, is described. The neutral catalysis facilitates glycidol addition to isocyanates followed by intramolecular cyclization. Mechanistic studies suggest that hydrogen-bonding interactions with the catalyst play an important role in the reaction progress.

An efficient method for the preparation of a range of 8-oxabicyclo[3.2.1]octane derivatives including synthetic intermediates of natural products is described, in which triethylamine effectively catalyzes [5+2] cycloaddition reactions between oxidopyrylium ylides and alkenes. This method can be applied not only to intermolecular cycloadditions with various alkenes but also to intramolecular cycloadditions. The key finding is that the combined use of organic bases having appropriate basicity and oxidopyrylium ylide precursors bearing a suitable leaving group facilitates the base-assisted generation of oxidopyrylium ylides in a catalytic manner., Article, ADVANCED SYNTHESIS & CATALYSIS.360(12):2377-2381(2018)

Preparation of vicinal halohydrins, in which copper or iron chlorides catalyze the ring-opening reaction of epoxides with visible light effectively, is described. The use of trichloroacetonitrile a...

An efficient method for the generation of an oxidopyrylium ylide from 6-acetoxy-6-acetoxymethyl-2H-pyran-3(6H)-one using a Pd catalyst and [5+2] cycloadditions of the resulting ylide are described. Among substituted styrene derivatives as dipolarophiles, electron-rich styrenes showed higher yield (up to 80%). The [5+2] cycloaddition reactions can also be applied to exo-methylene cyclic compounds, and an improved method for the synthesis of polygalolide intermediate has been demonstrated., Article, CHEMICAL COMMUNICATIONS.54(9):1109-1112(2018)

Preparation of a range of oxazolidinones, including enantioenriched N-aryl-substituted oxazolidinones, in which tetraarylphosphonium salts (TAPS) catalyze the [3 + 2] coupling reaction of isocyanates and epoxides effectively, is described. The key finding is a Brønsted acid/halide ion bifunctional catalyst that can accelerate epoxide ring opening with high regioselectivity. Mechanistic studies disclosed that the ylide generated from TAPS, along with the formation of halohydrins, plays a crucial role in the reaction with isocyanates.

The first example of asymmetric 1,3-dipolar cycloadditions between nitrile oxides and o-hydroxystyrenes, mediated by cinchona-alkaloid-based amine-ureas is reported. The method is based on a dual activation involving both LUMO and HOMO activations. In addition to the stoichiometric asymmetric induction, a catalytic amount of amine-urea enables the cycloadditions to proceed in an enantioselective manner. Computational studies strongly support the HOMO activation of o-hydroxystyrenes and LUMO activation of nitrile oxides by hydrogen-bonding interactions with the Brønsted acid/base bifunctional catalyst.

Carbonyl-stabilized phosphonium ylides exhibit great utility in modern organic synthesis, and they are known as an ambident nucleophile at the carbonyl oxygen atom and at the α-carbon atom. However, they have found limited use as catalysts. We focused on the inherent nucleophilicity of the oxygen atom to develop an ionic nucleophilic catalysis, and the phosphonium ylide-catalyzed primary alcohol selective acylation of mixed diols with acid anhydrides has been demonstrated. Mechanistic studies revealed the behavior of a catalyst, which would contribute to the field of ylide chemistry.

Phosphonium salts exhibit great utility in organic synthesis. However, tetraarylphosphonium salts (TAPS) have found limited use as catalysts. We demonstrate the TAPS-catalyzed carbon dioxide fixation at atmospheric pressure for the coupling reaction with epoxides. Five-membered cyclic carbonates were obtained, including enantio-enriched carbonates. Mechanistic studies revealed the origin of the behavior of TAPS to be the in situ formation of an active species by TAPS addition to epoxides via halohydrin intermediates.

A novel asymmetric photodimerization reaction of coumarin derivatives bearing the (S)-4-benzyl-2-oxazolidinone auxiliary provides only the syn-head-to-tail (syn-HT) dimer with moderate diastereoselectivity (up to 75 : 25). The mechanism of complete syn-HT selectivity and moderate diastereoselectivity is proposed based on the result of density functional theory (DFT) calculation. The benzyl group of the (S)-4-benzyl-2-oxazolidinone auxiliary in combination with a Lewis acid exerts effective diastereofacial shielding of the reaction site.

A dual catalytic system, dirhodium tetrapivalate/ytterbium(III) triflate, enables the three-component reactions of α-alkyl-α-diazoesters, aromatic aldehydes, and N-benzylidenebenzylamine derivatives to afford the corresponding β-amino alcohols in good yields after hydrolysis of the oxazolidine cycloadducts, whereas no β-amino alcohols are obtained in the absence of ytterbium(III) triflate. A similar dual catalytic system, dirhodium tetraacetate/ytterbium(III) triflate, is found to be effective in accelerating the reactions of α-aryl-α-diazoesters in high yields. Furthermore, the reactions using dimethyl diazomalonate are described.

Asymmetric 1,3-dipolar cycloaddition reactions between N-methylindoles and several cyclic carbonyl ylides that were derived from diazodiketone or diazoketoester precursors in the presence of both achiral Rh and chiral lanthanoid metal catalysts are described. For the six-membered cyclic carbonyl ylides derived from 1-diazo-5-aryl-2,5-pentanedione precursors, the cycloaddition reactions were carried out using Rh2(OAc)4 (2 mol %) and the chiral Pybox-Ph2-Lu(OTf)3 complex (10 mol %) as catalysts, resulting in high enantioselectivities (83% to >98% ee (exo)) along with relatively good exo-selectivities (exo:endo = 65:35 to 94:6) and yields (63-85%). For the five-membered cyclic carbonyl ylide derived from 1-diazo-2,4-pentandione precursor, the cycloaddition reaction with 5-bromo-1-methylindole was carried out in the presence of Rh2(OAc)4 (2 mol %) and the chiral Pybox-Ph2-Er(OTf)3 complex (30 mol %) as catalysts, resulting in relatively good enantioselectivity (78% ee) and endo-selectivity (endo:exo = 81:19).

Photoexcited nitrones serve as excellent electron acceptors as well as radical acceptors in the presence of tertiary amines to give β-amino hydroxylamines via photochemically-induced direct sp(3) C-H functionalization of the tertiary amines. The combined use of an organophotosensitizer and photoirradiation was highly effective in accelerating addition reactions. Several nitrones and tertiary amines were successfully utilized to give β-amino hydroxylamines in good yield. Highly regioselective generation of primary α-aminoalkyl radicals based on Lewis's stereoelectronic rule and diastereoselective addition reactions of primary α-aminoalkyl radicals with nitrones were successfully achieved. Furthermore, a highly diastereoselective reaction of an α-aminoalkyl radical with a chiral (E)-geometry-fixed α-alkoxycarbonylnitrone was performed.

Three enzymes responsible for the transhydrogenase-like shunt, including malic enzyme (encoded by MAE1), malate dehydrogenase (MDH2), and pyruvate carboxylase (PYC2), were overexpressed to regulate the redox state in xylose-fermenting recombinant Saccharomyces cerevisiae. The YPH499XU/MAE1 strain was constructed by overexpressing native Mae1p in the YPH499XU strain expressing xylose reductase and xylitol dehydrogenase from Scheffersomyces stipitis, and native xylulokinase. Analysis of the xylose fermentation profile under semi-anaerobic conditions revealed that the ethanol yield in the YPH499XU/MAE1 strain (0.38 ± 0.01 g g⁻¹ xylose consumed) was improved from that of the control strain (0.31 ± 0.01 g g⁻¹ xylose consumed). Reduced xylitol production was also observed in YPH499XU/MAE1, suggesting that the redox balance was altered by Mae1p overexpression. Analysis of intracellular metabolites showed that the redox imbalance during xylose fermentation was partly relieved in the transformant. The specific ethanol production rate in the YPH499XU/MAE1-MDH2 strain was 1.25-fold higher than that of YPH499XU/MAE1 due to the additional overexpression of Mdh2p, whereas the ethanol yield was identical to that of YPH499XU/MAE1. The specific xylose consumption rate was drastically increased in the YPH499XU/MAE1-MDH2-PYC2 strain. However, poor ethanol yield as well as increased production of xylitol was observed. These results demonstrate that the transhydrogenase function implemented in S. cerevisiae can regulate the redox state of yeast cells.

The catalytic activity of chiral binaphthyldiimine (BINIM)-Ni(II) complexes for asymmetric enantioselective diazoalkane cycloadditions of ethyl diazoacetate with 3-acryloyl-2-oxazolidinone and 2-(2-alkenoyl)-3-pyrazolidinone derivatives was evaluated. The cycloadditions of 3-acryloyl-2-oxazolidinone and its 5,5-dimethyl derivative, in the presence of the BINIM-Ni(II) complex (10 mol %; prepared from (R)-BINIM-4Ph-2QN (ligand C) and Ni(ClO(4))(2)·6H(2)O) afforded 2-pyrazolines having a methine carbon substituted with an oxazolidinonyl group in moderate ratios (70:30 to 72:28), along with high enantioselectivities (90-92% ee) via 1,3-proton migration. On the basis of the investigations on the counteranions of the Ni(II) complex, the N-substituent of pyrazolidinone, and reaction temperatures, the optimal enantioselectivity (97% ee) and ratio (85:15) of 2-pyrazoline were obtained for the reaction of 2-acryloyl-1-benzyl-5,5-dimethyl-3-pyrazolidinone in the presence of (R)-BINIM-4Ph-2QN-Ni(II) ((R)-C/Ni(II)) complex prepared using Ni(BF(4))(2)·6H(2)O. In the cases of 1-benzyl-2-crotonoyl-5,5-dimethyl-3-pyrazolidinone, 1-benzyl-2-(2-butenoyl)-5,5-dimethyl-3-pyrazolidinone, and 1-benzyl-5,5-dimethyl-2-(3-ethoxycarbonyl)propenoyl-3-pyrazolidinone, the use of the (R)-BINIM-2QN-Ni(II) ((R)-A/Ni(II)) complex gave good to high enantioselectivities (85-93% ee) with the sole formation of the 2-pyrazoline having a methine carbon substituted with a pyrazolidinonyl group. Relatively good enantioselectivity (77% ee) was observed for the reaction between 2-acryloyl-5,5-dimethyl-1-naphthylmethyl-3-pyrazolidinone and an α-substituted diazo ester, ethyl 2-diazo-3-phenylpropanoate, which has yet to be employed as a diazo substrate in asymmetric cycloaddition reactions catalyzed by a chiral Lewis acid.

1,3-Dipolar cycloadditions between acrolein and various N,N'-cyclic azomethine imines in the presence of L-proline and its derivatives as organocatalysts were investigated. Reactions that were catalyzed by (S)-indline-2-carboxylic acid (30 mol%) in CHCl3/MeOH 97:3 (v/v) showed high exo-selectivities (exolendo 91:9 similar to 99:1) and enantioselectivities (75 similar to 98% ee). In contrast, reactions catalyzed by L-proline (30 mol%) under similar conditions favored the endo-cycloadduct (83:27 similar to 99:1) with modest to good enantioselectivities (31 similar to 83% ee). Based on our studies, the diastereoselective mechanism of the L-proline-catalyzed reaction was found to involve the isomerization of the exo- to the endo-cycloadduct in the presence of L-proline., Article, HETEROCYCLES. 81(7):1669-1688 (2010)

High enantioselectivities (94–96% ee) were obtained for the inverse electron-demand 1,3-dipolar cycloadditions between cyclohexyl vinyl ether and 2-benzopyrylium-4-olate generated via Rh₂(OAc)₄-catalyzed decomposition of o-methoxycarbonyl-α-diazoacetophenone. The reactions were effectively catalyzed by Eu(OTf)₃, Ho(OTf)₃, or Gd(OTf)₃ complexes (10 mol %) of chiral 2,6-bis[(4S,5S)-4,5-diphenyl-2-oxazolinyl]pyridine. The reactions with the other electron-rich dipolarophiles such as allyl alcohol, 2,3-dihydrofuran, and butyl-tert-butyldimethylsilylketene acetal showed moderate enanantioselectivities (60–73% ee). Good to high enantioselectivities (73–97% ee) were also obtained for the cycloadditions between 3-acyl-2-benzopyrylium-4-olates, generated from methyl 2-(2-diazo-1,3-dioxoalkyl)benzoates and butyl or cyclohexyl vinyl ethers, in the presence of binaphthyldiimine (BINIM)–Ni(II) complexes (10 mol %). Under similar conditions, the reaction between methyl 2-(2-diazo-1,3-dioxohexyl)benzoate and 2,3-dihydrofuran was highly endo-selective, and moderately enantioselective (70% ee). For the BINIM–Ni(II)-catalyzed reactions of cyclohexyl vinyl ether, the use of an epoxyindanone as the 3-acyl-2-benzopyrylium-4-olate precursor revealed that the chiral Lewis acid can function as a catalyst for asymmetric induction. The scope of the cyclic carbonyl ylides was extended to those generated from 1-diazo-2,5-pentanedione derivatives, which were reacted with butyl or TBS vinyl ether and catalyzed using the (4S,5S)-Pybox-4,5-Ph₂–Lu(OTf)₃ complex to give good levels of asymmetric inductions (75–84% ee)., Article, Tetrahedron. 66(16):3070-3089 (2010)

The alkaline treatment of the pyridinium salts, readily available from the S-alkylations of 3-amino-4-(1-pyridinio)thiophene-5-thiolates with various alkyl halides, in chloroform at room temperature afforded the corresponding thieno[3′,4′:4,5]imidazo[1,2-a]pyridine derivatives in low to moderate yields via the intramolecular cyclization of the resulting 1,5-dipoles followed by the aromatization of the primary cycloadducts. Interestingly, the reactions using unsymmetrical 3-amino-4-[1-(3-methylpyridinio)]thiophene-5-thiolates afforded only 8-methylthieno[3′,4′:4,5]imidazo[1,2-a]pyridines and the other 6-methyl derivatives were not formed at all. In addition the isolation of a byproduct in the condensation reaction of pyridinium salt with the solvent (CHCl3) is also discussed.

The reactions of potassium 1,3-bis(ethoxycarbonyl)indolizine-2-thiolates with ethyl 4-bromocrotonate afforded the corresponding indolizine derivatives having (E)-(3-ethoxycarbonyl-2-propenyl)thio, (E)- and (Z)-(3-ethoxycarbonyl-1-propenyl)thio group at the 2-position. The alkaline treatment of these S-alkylated indolizines gave the title compounds in good yields., Article, HETEROCYCLES. 78(2): 319-324 (2009)

The alkaline treatment and dehydrogenation of pyridinium salts, formed from the S-alkylations of 3-(1-pyridinio)thiophene-2-thiolates with alpha,alpha-dibromo-o-, m-, or p-xylene, provided the corresponding alpha,alpha'-bis[(thieno[3,4-b]indolizin-3-yl)thio]-o-, m-, and p-xylene derivatives in low to good yields. Both (1)H-NMR and UV-Vis spectra of these products supported distinctly the predominance of the gauche-gauche conformation in relation to the two sulfide linkages as the spacer in these molecules. On the other hand, the X-ray analyses indicated the expected gauche-gauche conformation for the m- and the p-xylene derivatives, but the anti-anti one for the o-xylene derivative.

The syntheses of the title compounds from the reactions of 2-amino-3-(arylcarbonyl)indolizine-1-carbonitriles with various acetophenones in the presence of strong base were investigated. When the reactions were carried out between 2-aminoindolizines and 1.2-equimolar amounts of acetophenones, the yields for the target molecules were low or very low. However, when a large excess of acetophenones were used without any solvent or in as small as amount of solvent as possible, their yields were considerably improved. The smooth hydrolysis of the 10-cyano group to the carbamoyl one was also observed., Article, HETEROCYCLES. 77(1): 471-481 (2009)

The external work (EW) efficiency of individual arrhythmic beats of the left ventricle (LV) cannot directly be obtained since LV O(2) consumption (VO(2)) of each beat cannot directly be measured under beat-to-beat varying contractile and loading conditions. We, however, have recently reported that VO(2) of each arrhythmic beat can reasonably be estimated by VO(2) = aPVA + bE(max) + c even under varying PVA and E(max). Here, PVA is the LV pressure-volume (P-V) area as a measure of the LV total mechanical energy, E(max) is the LV end-systolic elastance as an index of the LV contractility, a is a constant O(2) cost of PVA, b is a constant O(2) cost of E(max), and c is the basal metabolic VO(2) of the beat, all on a per-beat basis. Using the above formula in this study, we calculated VO(2) of the individual arrhythmic beats from their measured PVA and E(max) during electrically induced atrial fibrillation (AF) in normal canine hearts. We then calculated their LV EW efficiency by dividing their measured EW with the estimated VO(2). We found that the thus calculated EW efficiency of the arrhythmic beats had a rightward skewed distribution with a mode of 15% and a maximum of 18% around a mean of 13% on average in six hearts. This mode remained comparable to the efficiency (15%) at regular tachycardia though 22% lower than mean arrhythmic tachycardia.

The alkaline treatment and dehydrogenation of pyridinium salts, obtainable from the S-alkylation of 3,5-dimethylpyridinium 2-alkylthio-1-cyano2-thioxoethylides with some phenacyl bromides, afforded unexpected heterocycles, 3-alkylthio-1-arylcarbonyl-6,8-dimethylthieno[3',4':4,5]imidazo-[1,2-a]pyridines, together with the corresponding 2-alkylthio-1-arylcarbonylthio-6,8-dimethylindolizine-3-carbonitriles., Article, HETEROCYCLES. 76(1): 391-399 (2008)

We have found the first successful example of reverse-electron-demand dipole-LUMO/dipolarophile-HOMO controlled cycloaddition reactions between carbonyl ylides, which were generated from o-methoxycarbonyl-alpha-diazoacetophenone and their acyl derivatives as precursors, and vinyl ether derivatives with high levels of asymmetric induction (97-77% ee) using chiral 2,6-(oxazolinyl)pyridine-Eu(III) or binaphthyldiimine-Ni(II) complexes as chiral Lewis acid catalysts.

Various thieno[3,4-b]indolizine derivatives having an acylmethylthio or (3-ethoxycarbonyl-2-propenyl)thio group at the 3-position which could not be obtained by a conventional method were prepared by a new procedure using cyanoethyl group as a protecting group and their intramolecular arene-pi interactions were investigated. In the (1)H-NMR spectra of these thieno[3,4-b]indolizines, the low-field shifts (delta 0.10-0.33 ppm) for the 5-protons were observed in comparison with those of 3-(methylthio)thieno[3,4-b]indolizines as a standard. The UV spectra also exhibited a characteristic absorption band at 425-445 nm attributable to the arene-pi interaction but their intensities were generally lower than those of 3-(arylmethylthio)thieno[3,4-b]indolizines. In their X-ray analyses, the anti conformation for 3-(acylmethylthio)thieno[3,4-b]indolizines and the gauche one for the 3-(3-ethoxycarbonyl-2-propenyl)thio derivatives were exhibited.

Among several Lewis acids examined, Sc(OTf)(3) (10 mol%) was found to be the most effective catalyst to promote a Michael addition reaction of N-Boc-2-(tert-butyldimethylsilyloxy)pyrrole to 3-acryloyl-2-oxazolidinone. A slow addition of the 2-silyloxypyrrole in the presence of 1,1,1,3,3,3-hexafluoro-2-propanol (5 equiv.) at -25 degrees C were needed to obtain good yield (77 - 80%). The asymmetric version of the reaction could be performed with good enantioselectivity (up to 82% ee) by using the chiral Sc(III) catalyst (10 mol%), which was prepared from 2,6-bis[(4S)-4-isopropyl-2-oxazolin-2-yl]pyridine and Sc(OTf)(3), in reasonable yield (60 - 70%)., Article, Heterocycles. 71(2): 361-371 (2007)

Asymmetric 1,3-dipolar cycloaddition reactions between N-methylindoles and several cyclic carbonyl ylides that were derived from diazodiketone or diazoketoester precursors in the presence of both achiral Rh and chiral lanthanoid metal catalysts are described. For the six-membered cyclic carbonyl ylides derived from 1-diazo-5-aryl-2,5-pentanedione precursors, the cycloaddition reactions were carried out using Rh2(OAc)4 (2 mol %) and the chiral Pybox-Ph2-Lu(OTf)3 complex (10 mol %) as catalysts, resulting in high enantioselectivities (83% to >98% ee (exo)) along with relatively good exo-selectivities (exo:endo = 65:35 to 94:6) and yields (63-85%). For the five-membered cyclic carbonyl ylide derived from 1-diazo-2,4-pentandione precursor, the cycloaddition reaction with 5-bromo-1-methylindole was carried out in the presence of Rh2(OAc)4 (2 mol %) and the chiral Pybox-Ph2-Er(OTf)3 complex (30 mol %) as catalysts, resulting in relatively good enantioselectivity (78% ee) and endo-selectivity (endo:exo = 81:19).

Article, Tetrahedron. 62(39): 9218-9225 (2006)

The logistic time constant (tau(L)) has been proposed as a better index of the rate of left ventricular (LV) relaxation or lusitropism than the conventional monoexponential time constant (tau(E)). However, whether and how the Frank-Starling effect influences tau(L) remains to be elucidated. We compared the effect of LV volume (LVV) loading on both logistic and monoexponential fittings. The isovolumic LV relaxation pressure curves from the maximum negative time derivative of pressure (-dP/dt(max)) were analyzed at 3 different end-points at 4 LVVs of 10, 12, 14, and 16 mL in 8 excised, cross-circulated canine hearts. We found that the logistic fitting was superior to the monoexponential fitting at all LVVs and end-points. LVV loading did not affect tau(L) but affected tau(E) slightly. Although the advancing end-point increased both tau(L) and tau(E), the increases were significantly smaller for tau(L) than for tau(E) at all LVVs. Moreover, the changes in both the amplitude constants and nonzero asymptotes with the advancing end-point were significantly smaller for the logistic fitting than for the monoexponential fitting. We conclude that tau(L) served as a more reliable index of lusitropism that is independent of the change in LVV loading or the Frank-Starling effect.

Background Better protective effects of Celsior on cardiac function than the other conventional solutions have been reported in acute experiments and in clinical trials for at-risk patients. However, no study has yet precisely elucidated how these preservation solutions affect cardiac mechanoenergetics. Therefore, we evaluated the effects of St. Thomas' Hospital solution No. 2, University of Wisconsin solution, and Celsior on left ventricular contractility (E max : end-systolic pressure–volume ratio) and oxygen consumption. Methods We used 32 canine excised cross-circulated hearts. Twenty-three hearts served as donor hearts after hypothermic ischemia with one of the three solutions, and the remaining 9 served as controls. After arrest with each solution, the hearts were preserved for 4 hours at 4°C. Then, we measured left ventricular pressure, volume, and oxygen consumption to obtain E max and the relation between ventricular pressure–volume area (a measure of total mechanical energy) and oxygen consumption. We also evaluated the oxygen cost of E max by changing E max with calcium administration. Results Celsior did not significantly affect E max (6.3 ± 2.4 in control versus 5.3 ± 1.3 mm Hg · mL −1 · 100 g with Celsior) nor the oxygen cost of E max (1.2 ± 0.6 versus 1.6 ± 0.5 mL O 2 · mL · mm Hg −1 · beat −1 · 100 g −2 , respectively). In contrast, St. Thomas' Hospital and University of Wisconsin solutions significantly decreased E max (4.5 ± 1.1 and 3.5 ± 0.9 mm Hg · mL −1 · 100 g, respectively) and increased the oxygen cost of E max (2.5 ± 0.8 and 2.4 ± 0.9 mL O 2 · mL · mm Hg −1 · beat −1 · 100 g −2 , respectively) compared with control and Celsior-preserved hearts. The slope and intercept of the oxygen consumption versus pressure–volume area relation showed no significant difference among the four groups. Conclusions Celsior showed better protective effects on cardiac mechanoenergetics than St. Thomas' Hospital and University of Wisconsin solutions in the acute phase of heart transplantation.