Arun K. Das Gupta

Coumarins and related compounds. Part XIX. Synthesis of 3-phenyl-benzo[h]coumarin

3-Phenylbenzo[h]coumarin (14) has been synthesised from 1-methoxy-2-naphthaldehyde (12) and an improved synthesis of 1-hydroxy-2-naphthaldehyde (11) is described. Attempts to synthesise 3-phenyl-3,4-dihydro-benzo[h]coumarin (15) resulted in the formation of 4-substituted 1-naphthols (3) and (4) when 1-naphthol was condensed with 2-phenylacrylonitrile in the presence of zinc chloride, and of the naphthofuranone (9) when ethyl 2-phenylacrylate and anhydrous aluminium chloride were used.

Discovery of Potent and Orally Bioavailable Dihydropyrazole GPR40 Agonists

G protein-coupled receptor 40 (GPR40) has become an attractive target for the treatment of diabetes since it was shown clinically to promote glucose-stimulated insulin secretion. Herein, we report our efforts to develop highly selective and potent GPR40 agonists with a dual mechanism of action, promoting both glucose-dependent insulin and incretin secretion. Employing strategies to increase polarity and the ratio of sp3/sp2 character of the chemotype, we identified BMS-986118 (compound 4), which showed potent and selective GPR40 agonist activity in vitro. In vivo, compound 4 demonstrated insulinotropic efficacy and GLP-1 secretory effects resulting in improved glucose control in acute animal models.

Coumarins and related compounds. Part XXI. A reinvestigation of the reaction between 1-naphthol and 2-formyl-2-phenylacetonitrile

Controversy arose between Baker and Ghosh over whether a compound of m.p. 169–170° obtained in the title reaction was 3-phenylnaphtho[1,2-b]pyran-2-one (2) or the corresponding naphthopyran-4-one (1). Synthesis of compounds (1) and (2) showed that both these authors were wrong. The reaction has now been repeated and found to give a mixture of 3-(4-hydroxy-1-naphthyl)-2-phenylacrylonitrile (5), 3-hydroxy-3-(4-hydroxy-1-naphthyl)-2-phenylpropiononitrile (9), and 3,4-dihydro-4-(4-hydroxy-1-naphthyl)-3-phenylnaphtho[1,2-b]-pyran-2-one (11). Thermal condensation between 1-naphthol and 2-formyl-2-phenylacetonitrile gave exclusively the naphthopyranone (2) in moderate yield.

Coumarins and related compounds. Part IV. Aluminium chloride-catalysed reaction of phenols with methyl acrylate: a new approach to the synthesis of hydroxycoumarins

The synthesis of 5-,6- and 7-hydroxycoumarins by dehydrogenation of the corresponding 3,4-dihydro-derivatives obtained by aluminium chloride-catalysed reaction of dihydric phenols or their derivatives with methyl acrylate is reported. The compound previously described as 5-hydroxydihydrocoumarin has been proved to be 3,4,6,7-tetrahydrobenzo[1,2-b: 5,4-b′]dipyran-2,8-dione on the basis of spectral evidence and synthesis.

Coumarins and related compounds. Part XIII. Synthesis of 2-oxonaphtho[1,2-b]pyran-6-propionic acid

The synthesis of 3,4-dihydro-2-oxonaphtho[1,2-b]pyran-6-propionic acid (III), obtained as a by-product during a synthesis of a benzocoumarin is described.

Coumarin and related compounds. Part XIV. A novel 4-methoxy-1-naphthyl 4-methoxy-1-naphthylethyl ketone from the aluminium chloride-catalysed reaction of 1-methoxynaphthalene with acrylonitrile

The structure of the title compound (6) obtained from the aluminium chloride-catalysed reaction of 1-methoxynaphthalene with acrylonitrile has been elucidated.