Synthesis of benzothiophene derivatives by Pd-catalyzed or radical-promoted heterocyclodehydration of 1-(2-mercaptophenyl)-2-yn-1-ols.

Novel and convenient approaches to benzothiophene derivatives 3 and 5 have been developed, based on heterocyclization reactions of 1-(2-mercaptophenyl)-2-yn-1-ols 2 or 4, respectively, readily available from alkynylation of 2-mercaptobenzaldehydes or 1-(2-mercaptophenyl) ketones 1. In particular, 1-(2-mercaptophenyl)-2-yn-1-ols 2, bearing a CH(2)R substituent on the triple bond (R = alkyl, aryl), were conveniently converted in fair to good yields (55-82%) into (E)-2-(1-alkenyl)benzothiophenes 3 when allowed to react in the presence of catalytic amounts (2 mol %) of PdI(2) in conjunction with KI (KI:PdI(2) molar ratio =10) at 80-100 °C in MeCN as the solvent, through a heterocyclodehydration process. On the other hand, 2-alkoxymethylbenzothiophenes 5 were selectively obtained in fair to excellent yields (49-98%) via a radical-promoted substitutive heterocyclodehydration process, by reacting 1-(2-mercaptophenyl)-2-yn-1-ols 4 (bearing an alkyl or aryl substituent on the triple bond) in alcoholic media at 80-100 °C in the presence of a radical initiator, such as AIBN.

Xanthohumol from hop (Humulus lupulus L.) is an efficient inhibitor of monocyte chemoattractant protein-1 and tumor necrosis factor-alpha release in LPS-stimulated RAW 264.7 mouse macrophages and U937 human monocytes.

Activated macrophages in adipose tissue play a major role in the chronic inflammatory process that has been linked to the complications of overweight and obesity. The hop plant (Humulus lupulus L.) has been described to possess both anti-inflammatory and antidiabetic effects. In the present study, the chemical composition of a hop crude extract (HCE) was investigated by ultrahigh-performance liquid chromatography (UHPLC). Next, HCE and various fractions obtained by preparative HPLC were tested for their ability to inhibit production of two pro-inflammatory cytokines, monocyte chemoattractant protein-1 (MCP-1, CCL2) and tumor necrosis factor-alpha (TNF-alpha), which play crucial roles in the complications of obesity. The hop chalcone xanthohumol was found to be the most potent inhibitor of both cytokines in LPS-activated RAW 264.7 mouse macrophages and U937 human monocytes. Moreover, other constituents, namely, iso-alpha-acids, in combination with the beta-acid hulupone, showed a moderate but selective inhibitory activity only on MCP-1 release. These findings underscore the potential health effects of hop and support further optimization, selection, and use of this plant.

Versatile synthesis of quinoline-3-carboxylic esters and indol-2-acetic esters by palladium-catalyzed carbonylation of 1-(2-aminoaryl)-2-yn-1-ols.

1-(2-Aminoaryl)-2-yn-1-ols, easily obtained by the Grignard reaction between 1-(2-aminoaryl)ketones and alkynylmagnesium bromides, were subjected to carbonylative conditions in the presence of the PdI2-KI catalytic system, in the presence and in the absence of an external oxidant. Under oxidative conditions (80 atm of a 4:1 mixture of CO-air, in MeOH as the solvent at 100 degrees C and in the presence of 2 mol % of PdI2 and 20 mol % of KI), 1-(2-aminoaryl)-2-yn-1-ols bearing a primary amino group were selectively converted into quinoline-3-carboxylic esters in fair to good yields [45-70%, based on starting 1-(2-aminoaryl)ketones], ensuing from 6-endo-dig cyclization followed by dehydration and oxidative methoxycarbonylation. On the other hand, indol-2-acetic esters, deriving from 5-exo-dig cyclization followed by dehydrating methoxycarbonylation, were selectively obtained in moderate to good yields [42-88%, based on starting 1-(2-aminoaryl)ketones] under nonoxidative conditions (90 atm of CO, in MeOH as the solvent at 100 degrees C and in the presence of 2 mol % of PdI2 and 20 mol % of KI), in the case of 1-(2-aminoaryl)-2-yn-1-ols bearing either a primary or secondary amino group and substituted with a bulky group on the triple bond.