Syntheses of C2′-Fluorinated Analogs of Solamin

Abstract

The details of the total syntheses of C2′-fluorinated analogs of solamin, an antitumor annonaceous acetogenin, are described. Fluorine was enantioselectively introduced at the C2′-position by organocatalytic α-fluorination of the aldehyde according to a previously reported method. C2′-fluorinated solamin and its C2′-diastereomer were synthesized by the Sonogashira coupling of a tetrahydrofuran fragment and fluorinecontaining γ-lactone fragments.

Thiophene Carboxamide Analogs with Long Alkyl Chains Comprising Ethylene Glycol Units Inhibit Glioblastoma Cell Proliferation by Activating AMPK

“…The starting material, TBS-protected triethylene glycol 10, was easily synthesized from triethylene glycol, as previously described. 27 The etherification of 10 was performed using 1-azido-12-bromododecane 28 to produce azide (11) with a moderate yield. Next, the azido group of 11 was reduced, followed by the condensation of thiophene-3carboxylic acid to produce amide 13.…”

“…M.p. 35 (11). NaH (60% in oil, 151 mg, 3.78 mmol) was added to a solution of 10 (500 mg, 1.89 mmol) in DMF (1.9 mL) at 0 °C.…”

“…We had previously studied the SAR of annonaceous acetogenins to develop anticancer agents. − Annonaceous acetogenins are polyketides isolated from Annona plants that grow in tropical and subtropical regions; most contain one to three 2,5-disubstituted tetrahydrofurans (THFs) in the center of the long hydrocarbon chain and an α,β-unsaturated-γ-lactone at the end of the molecule. − The structure of solamin, an acetogenin, is shown in Figure . − Studies have revealed that the mitochondrial complex I inhibitor JCI-20679 ( 1 ), , a solamin analog, showed antitumor activity against glioblastoma by activating AMP-activated protein kinase (AMPK) . Additionally, 1 enhances the antitumor activity of TMZ .…”

Structure–antitumor activity relationship of hybrid acetogenins focusing on connecting groups between heterocycles and the linker moiety

“…Owing to our interest in complex I inhibitors, we have studied the structure–activity relationship (SAR) of annonaceous acetogenins and their analogs. 5 Annonaceous acetogenins are polyketides isolated from Annona plants, which show antitumor activity against human cancer cells by inhibiting mitochondrial complex I. 6,7 Most of them have one to three tetrahydrofuran (THF) rings in the center of the long hydrocarbon chain and an α,β-unsaturated-γ-lactone ring at the end of the molecule.…”