Amorfrutin B关键中间体的关环合成

Novel Synthesis of the Key Intermediate of Amorfrutin B by Aromatic Cyclization

以米氏酸和香叶醇为原料,采用钯催化的一锅串联反应为关键步骤,通过酯交换开环、酰化与缩合、卡罗尔重排、Aldol缩合、脱水芳构化等5步反应(总收率14.2%),高效率地合成了Amorfrutin B的关键中间体——(E)-7-羟基-2,2-二甲基-8-(3,7-二甲基-2,6-辛二烯-1-基)-5-苯乙基-4H-苯并[d][1,3]二口恶英-4-酮(Ⅹ)。各中间体和产物的结构通过FTIR和1HNMR得以确认。中间体(E)-3-(3,7-二甲基-2,6-辛二烯-1-氧基)-3-丙二酸酯(Ⅲ)、(E)-3,7-二甲基-2,6-辛二烯-1-基-4-(2,2-二甲基-4-氧代-4H-1,3-二氧六环-6-基)-3-氧代丁酸(Ⅵ)的反应条件得以优化,提高了产率,降低了成本,使合成路线更加经济合理。对关键串联反应的机理进行了解释,即中间体(E)-3,7-二甲基-2,6-辛二烯-1-基-4-〔2-(2,2-二甲基-4-氧代-4H-1,3-二氧六环-6-基)乙酰基〕-3-氧代-5-苯基戊酯(Ⅸ)通过两次卡罗尔重排、脱羧后分子内Aldol缩合及脱水后芳构化等一系列转变形成了具有苯酚结构的关键中间体Ⅹ。Ⅹ的成功合成为Amorfrutin B的完全合成奠定了重要基础。

Taking Pd（0）-catalyzed one-pot cascade reaction as the key step, the key intermediate of Amorfrutin B, （ E ） -7 -hydroxy-2,2-dimethyl-8 - （ 3,7 -dimethylocta-2,6-dienyl ） -5 -phenethyl-4H-benzo [ d] [ 1,3 ] dioxin-4-one （ X ）, was synthesized efficiently within five steps, starting from Meldrum＇s acid and geraniol. The structures of all the intermediates and the final compound were characterized by means of FFIR and 1HNMR. The reaction conditions of intermediates （E） -3- （ 3,7-dimethylocta-2,6- dienyloxy） -3 -oxopropanoic acid （ m ）, and （ E ） -3,7-dimethylocta-2,6-dienyl-4-（ 2,2-dimethyl-6-oxo- 6H-1,3-dioxin-4-yl）-3-oxobutanoate （WI） were also optimized to increase the yields and lower down the expenses, so as to determine a more practical synthetic process. The mechanism of the key cascade reaction was explained, that is, the intermediates （ E）-3,7-dimethylocta-2, 6-dienyl 2-[ 2-（2, 2- dimethyl-6- oxo-6H-1,3-dioxin-4-yl） acetyl]-3-oxo-5-phenylpentanoate（ IX）underwent tandem Carroll rearrangement twice, decarboxylation, intramolecular Aldol condensation and final dehydration followed by aromatization to generate the key intermediate X in one pot. The successful synthesis of X is believed to play an important role in the total synthesis of Amorfrutin B.