Hitoshi Ban

An Efficient Method for Generation of α-Oxoketenes: Cycloreversion of Enolized Meldrum's Acid Derivatives

Abstract A series of 6-methoxy- or siloxy-4 H -1,3-dioxin-4-ones was synthesized from Meldrums acids. These dioxinones underwent 4+2 cycloreversion to methoxy- or siloxycarbonylketenes and ketones quantitatively at 20–50 °C. The ketenes were characterized by IR spectroscopy as well as by trapping with t -butanol. The ready cycloreversion of these enolized Meldrums acid derivatives strongly indicates that the anomalously high susceptibility of Meldrums acids to nucleophilic reagents is due to the participation of carboxyketenes generated through the cycloreversion of tautomeric 6-hydroxydioxinones.

NOVEL DECOMPLEXATION METHOD FOR ALKYNE-CO2(CO)6 COMPLEXES

Abstract A novel and general decomplexation method for alkyne–Co 2 (CO) 6 complexes has been established, which treats the complexes with ethylenediamine in THF.

A convenient synthesis of 4-aryl-1,8-naphthyridin-2(1H)-ones by the Suzuki coupling

4-Halo-1,8-naphthyridin-2(1H)-ones readily available from 2-chloronicotinic acid were subjected to the Suzuki coupling reaction with arylboronic acids to give a diversity of 4-aryl-1,8-naphthyridin-2(1H)-ones.

Thermal cycloreversion of 4H-1,3-dioxine-4-thiones to acyl thioketenes:a general synthesis of β-keto thioic O-acid derivatives

Thermal cycloreversion of 4H-1,3-dioxine-4-thiones gives acyl thioketenes as reactive intermediates, trapping of which by nucleophiles provides a general synthesis for β-keto thioic O-acid derivatives.

A Novel Class of Antihyperlipidemic Agents with Low Density Lipoprotein Receptor Up-Regulation via the Adaptor Protein Autosomal Recessive Hypercholesterolemia

We have previously reported compound 2 as a inhibitor of acyl-coenzyme A:cholesterol O-acyltransferase (ACAT) and up-regulator of the low density lipoprotein receptor (LDL-R) expression. In this study we focused on compound 2, a unique LDL-R up-regulator, and describe the discovery of a novel class of up-regulators of LDL-R. Replacement the methylene urea linker in compound 2 with an acylsulfonamide linker kept a potent LDL-R up-regulatory activity, and subsequent optimization work gave compound 39 as a highly potent LDL-R up-regulator (39; EC(25) = 0.047 microM). Compound 39 showed no ACAT inhibitory activity even at 1 microM. The sodium salts of compound 39 reduced plasma total and LDL cholesterol levels in a dose-dependent manner in an experimental animal model of hyperlipidemia. Moreover, we revealed in this study using RNA interference that autosomal recessive hypercholesterolemia (ARH), an adaptor protein of LDL-R, is essential for compound 39 up-regulation of LDL-R expression.

A convenient one-pot preparation of n-substituted 4-phenylpiperidines

N-Substituted 4-phenylpiperidines were readily synthesized by one-pot cyclization of diols with amines via bis-triflate intermediates. The new synthesis under mild conditions gave various N-substituted 4-phenylpiperidines in moderate to good yields.

A practical synthesis of 1-alkyl-3-amino-4-aryl-1,8-naphthyridin-2-(1H)-one, a partial structure of ACAT inhibitor SMP-797

3-Amino-4-[3-(3-benzyloxypropoxy)phenyl]-1-butyl-1,8-naphthyridin-2(1H)-one, which is a naphthyridine part of a potent ACAT (acyl-CoA: cholesterol acyltransferase) inhibitor SMP-797, was effectively synthesized from m-bromophenol in 5 steps without isolating intermediates. The synthesis involved the intramolecular aldol reaction as a key step.