Convenient synthesis of oxazolidinones by the use of halomethyloxirane, primary amine, and carbonate salt

[reaction: see text] Primary amines reacted with carbonate salts (Na2CO3, K2CO3, Cs2CO3, and Ag2CO3) and halomethyloxiranes in the presence of a base such as DBU or TEA to give oxazolidinones in high yields. The use of K2CO3 among these carbonate gave the best yield in this synthesis. A reaction mechanism was proposed that the oxazolidinone was obtained from an oxazinanone intermediate via a bicyclo[2.2.1] intermediate. The present reaction can be widely applied to convenient synthesis of useful N-substituted oxazolidinones and chiral oxazolidinones.     

Large two-photon absorption (TPA) cross-section of directly linked fused diporphyrins

The excited state dynamics and two-photon absorption properties of four novel triply linked porphyrin dimers in toluene have been investigated. The fused porphyrin dimers exhibit extremely increased two-photon absorption cross-section values (12,000-15,000 GM) compared with porphyrin monomers owing to much enhanced pi-electron delocalization throughout the porphyrin dimer ring.     

Estimation of active conformations of drugs by a new molecular superposing procedure

We have developed a new program, SUPERPOSE, to superpose two molecules based on the physicochemical properties of functional atoms within individual molecules. SUPERPOSE treats a pseudo-molecule consisting of functional atoms instead of a real molecule. Four types of physicochemical properties – hydrophobicity, presence of a hydrogen-bonding donor, presence of a hydrogen-bonding acceptor and presence of a hydrogen-bonding donor/acceptor – were supposed and a score was given to each overlap. When functional atoms with the same physicochemical properties were overlapped, points were added to the score, and when the functional atoms with different physicochemical properties were overlapped, points were subtracted. We applied SUPERPOSE to 12 pairs of 24 enzyme inhibitors and found that the best scored overlay for each inhibitor pair could successfully reproduce the superposition obtained from X-ray crystallography. Next, we applied SUPERPOSE to estimate the active conformations of the thrombin inhibitors MQPA, 4-TAPAP and NAPAP. Superpositions of conformers sampled by the high-temperature molecular dynamics calculation with respect to the three inhibitors were performed, and 13 sets of conformers having the best common overlay to the three inhibitors were selected. One among 13 sets was consistent with the superposition of the active conformations derived from the X-ray crystallography of the thrombin–inhibitor complexes.     

Discovery of N-(3-{4-[(3-fluorobenzyl)oxy]phenoxy}propyl)-2-pyridin-4-ylacetamide as a potent and selective reverse NCX inhibitor

In the setting of heart failure and myocardial ischemia-reperfusion, the sodium-calcium exchanger (NCX) can lead to calcium overload, which is responsible for contractile dysfunction and arrhythmia. NCX is an attractive target for treatment in heart failure and myocardial ischemia-reperfusion. We have designed and synthesized a series of benzyloxyphenyl derivatives based on compound 3. These derivatives have been evaluated for their inhibitory activity against both the reverse and forward modes of NCX. We have discovered a novel potent and selective reverse NCX inhibitor (12) with an IC50 value of 0.085 microM against reverse NCX.     

Synthesis of 9α,11α-thiathromboxane A2 methyl ester

The synthesis of thromboxane A₂ (TXA) analogue, 9α,11α-thia-TXA₂ methyl ester $\text{2}$, in which the oxygen atom in the oxetane ring of TXA₂ was replaced by a sulfur atom, is described.     

Lipase‐Catalyzed transformation of Poly(trimethylene carbonate) into Cyclic Monomer,Trimethylene Carbonate: A New Strategy for Sustainable Polymer Recycling Using an Enzyme

The enzymatic degradation and polymerization using an enzyme were carried out with respect to the establishment of a sustainable chemical recycling system for poly(trimethylene carbonate) [P(TMC)] which is a potentially biodegradable synthetic plastic. The enzymatic transformation of P(TMC)s having an M_n of 3000~48000 using Candida antarctica lipase (lipase CA) in acetonitrile at 70 °C afforded the corresponding cyclic monomer, trimethylene carbonate (TMC: 1,3‐dioxan‐2‐one), in a yield of up to 80%. Thus obtained TMC readily polymerized again using both fresh lipase CA and recovered lipase CA.     

Chain-growth polycondensation of potassium 3-cyano-4-fluorophenolate derivatives for well-defined poly(arylene ether)s

Polycondensation normally proceeds in a step-growth reaction manner to give polymers with a wide range of molecular weights. However, the polycondensation of potassium 2-alkyl-5-cyano-4-fluorophenolate ( 1 ) proceeded at 150°C in a chain polymerization manner from initiator, 4-fluoro-4′-trifluoromethyl benzophenone ( 2 ), to give aromatic polyethers having controlled molecular weights and low polydispersities (M_w/M_n ⩽ 1.2). The resulting polycondensation of 1 had all of the characteristics of living polymerization and displayed a linear correlation between molecular weight and monomer conversion, maintaining low polydispersities. Sulfolane was a better solvent for chain-growth polycondensation of 1 than other aprotic solvents. The polyether from 1 with a low polydispersity showed higher crystallinity than that with a broad molecular weight distribution, obtained by the conventional polycondensation of 1 without 2 .