130233-83-9

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The diaryletherheptanoid natural product, pterocarine, is expeditiously synthesized using a bioinspired intramolecular oxidative phenolic coupling of acerogenin G. The cyclization precursor is prepared from a simple cinnamic acid derivative in three high yielding synthetic operations. The key oxidative coupling is inspired by biosynthetic hypotheses; however, the oxidative coupling proceeds with concomitant hydroxylation of the diphenyl ether motif.

A strategy for the synthesis of natural and non-natural 5-deoxy-6,7-dihydrocurcuminoids (diarylheptanoids) was developed for the preparation of 14 compounds with varying aromatic substituent patterns and a different functionality in the aliphatic seven-carbon chain. The in vitro protective activity against glutamate-induced neuronal cell death was examined in the murine hippocampal cell line HT-22 to find structural motifs responsible for neuroprotective effects in vitro. Among the tested compounds the ferulic acid-like unit, present in the structures of (E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hept-1-en-3-one (5) and (E)-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hept-1-en-3-one (7), appeared to be an important feature for protection against glutamate-induced neurotoxicity. Both compounds demonstrated significant neuroprotective activity in a concentration range between 1 and 25 ～M without showing toxic effects in a cytotoxicity assay with HT-22 cells. Furthermore, (E)-1,7-bis(3,4-dihydroxyphenyl)hept-1-en-3-one (9), exhibiting a caffeic acid-like structural motif, displayed a neuroprotective activity at a nontoxic concentration of 25 ～M. In contrast, (1E,6E)-1,7-bis(3,4-dihydroxyphenyl)hepta-1,6-diene-3,5-dione (4, di-O-demethylcurcumin) showed mainly cytotoxic effects. A corresponding single-ring analogue that contains the ferulic acid-like unit as an enone was not active.

The first total synthesis of the diarylheptanoid acerogenins E and K, isolated from Acer nikoense MAXIM., is described. Formation of the 13-membered m,m-cyclophane skeleton was successfully achieved on the basis of a domino process involving a Miyaura arylborylation-intramolecular Suzuki reaction. The cyclization precursor was prepared via a Wittig reaction and Claisen-Schmidt condensation, which proceeded in moderate yields. The total synthesis of acerogenin G and centrolobol was also achieved from a common synthetic intermediate.

Syntheses of the metabolites from platyphylloside, a phenol causing digestibility inhibition in rumen fluid, have been performed to identify the active metabolite. 1,7-Bis(4′-hydroxyphenyl)-3-heptanone (3-platyphyllone), racemic, and the two enantiomers o

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