P-17 バンレイシ科アセトゲニンrollicosin,murisolinの合成研究(ポスター発表の部)

概要

論文の詳細を見る
Annonaceous acetogenins, that have been isolated from a number of the Annonaceae, have attracted much attention due to a wide variety of biological activities. So far, more than 400 compounds have been isolated. Most of them possess one or more tetrahydrofuran rings, together with an α,β-unsaturated γ-lactone part on a C-35 or C-37 carbon chain. In this symposium, we wish to report the synthetic studies on rollicosin (1), 15, 16-di-epi-rollicosin (2), murisolin (3), and their inhibitory activity against bovine mitochondrial complex I. 1. Synthesis of (4R, 15R, 16R, 21S)-rollicosin (1) and (4R, 15S, 16S, 21S)-rollicosin (2) Rollicosin (1) was isolated from Rollinia mucosa by Y.-C. Wu et al. This compound possesses a partial skeleton of annonaceous acetogenins containing two γ-lactone moieties on both sides of an aliphatic chain. This compound may help investigate the role of the terminal hydroxylated lactone moiety for its bioactivity in stead of the hydroxylated THF moiety with long aliphatic chain that can be seen in the classical acetogenins. We have achieved a convergent synthesis of (4R, 15R, 16R, 21S)-rollicosin (1) and (4R, 15S, 16S, 21S)-rollicosin (2). Hydroxy lactone 9a and/or 9b were synthesized from 4-pentyn-1-ol, and α, β-unsaturated lactone 21 was synthesized from known γ-lactone and 5-hexen-1-ol. 2. Synthetic studies on murisolin (3) Synthetic Studies on murisolin (3) is described. The THF ring moiety was constructed using Sharpless asymmetric epoxidation, dihydroxylation as key steps. Sonogashira cross coupling reaction of THF ring moiety 35 with γ-lactone part 36 afforded enyne. Studies directing toward total synthesis is underway. 3. Inhibitory Action with Bovine Heart Mitochondrial Complex I Inhibitory effect of 1 and 2 on bovine heart mitochondrial complex I was examined. Both compounds exhibited almost same inhibitory potency (1: IC_<50>=0.66±0.03μM, 2: IC_<50>=0.68±0.03μM), indicating that the stereochemistry around the hydroxylated lactone moiety does not affect the inhibitory action. It is noteworthy that compared to potent natural acetogenins like bullatacin (IC_<50>=0.8nM), both compounds are much weaker inhibitors of the enzyme. We concluded that the hydroxylated lactone cannot be substituted for the hydroxylated mono- or bis-THF ring moiety of ordinary acetogenins for the activity. The inhibitory effect of murisolin (3) will be discussed after completion of synthesis.
天然有機化合物討論会の論文
2005-09-15

P-17 バンレイシ科アセトゲニンrollicosin,murisolinの合成研究(ポスター発表の部)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク