Pergomet Jorgelina L, Bracca Andrea B J, Kaufman Teodoro S
Instituto de Química Rosario (IQUIR, CONICET-UNR), and Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK Rosario, República Argentina.
Org Biomol Chem. 2017 Aug 23;15(33):7040-7049. doi: 10.1039/c7ob01471f.
The concise and efficient total syntheses of the naturally-occurring coumarin derivatives gerberinol I, and the pterophyllins 2 and 4, from 5-methyl-4-hydroxycoumarin as a common precursor employing different Casnati-Skattebøl reaction conditions, are reported. The synthesis of the key intermediate coumarin was achieved by the organocatalytic condensation of acetylacetone and crotonaldehyde followed by a LiCl-assisted cyclization, CuCl-promoted aromatization and a final EtCO-mediated cyclization. A Casnati-Skattebøl formylation under high-temperature conditions afforded gerberinol I, whereas milder conditions resulted in an unstable 3-formyl-4-hydroxycoumarin derivative, which was subjected to a basic alumina-mediated one pot O-alkylation with chloroacetone and intramolecular aldolization to furnish pterophyllin 4. Wittig methylenation of the latter conveniently afforded pterophyllin 2.
报道了以5-甲基-4-羟基香豆素为共同前体，采用不同的卡斯纳蒂-斯卡特博尔反应条件，简洁高效地全合成天然存在的香豆素衍生物格贝瑞诺醇I以及翼叶花椒素2和4。关键中间体香豆素的合成是通过乙酰丙酮和巴豆醛的有机催化缩合，随后进行LiCl辅助环化、CuCl促进芳构化以及最终EtCO介导的环化来实现的。在高温条件下进行的卡斯纳蒂-斯卡特博尔甲酰化反应得到了格贝瑞诺醇I，而较温和的条件则产生了一种不稳定的3-甲酰基-4-羟基香豆素衍生物，该衍生物与氯丙酮进行碱性氧化铝介导的一锅法O-烷基化反应并进行分子内羟醛缩合反应，从而得到翼叶花椒素4。后者的维蒂希亚甲基化反应方便地得到了翼叶花椒素2。
