Chemical Studies of alpha-Pyrone Meroterpenoids

首次实现了微生物A -吡啶酮萜类化合物、(+)-吡啶烯A(1)、酰基辅酶A：胆固醇酰基转移酶（ACAT）抑制剂的全合成，这是一种有效而简洁的聚合方法（14步，产率9.3%），可方便地获得天然产物和各种类似物。关键步骤是在Lewis酸存在下，a-吡啶-吡啶部分(4)与倍半萜类部分(3)的氯酸偶联反应生成酮(2)。经立体选择性还原甲酰化、钯相关羰基化和(+)-Wieland-Wiescher酮的烯丙基氧化合成倍半萜。（+）-吡咯烯E（15）也由法尼酯乙酸酯合成（9步，总收率9.6%）。聚合和立体选择途径利用仿生多烯环化作为关键转化。我们还利用这些合成方案制备了300多个衍生物，并明确了它们的构效关系。

The first total synthesis of the microbial a-pyrone meroterpenoid, (+)-pyripyropene A (1), acyl-CoA : cholesterol acyltransferase (ACAT) inhibitor, which is effective and concise convergent approach (14 steps, 9.3% yield), designed to afford easy access to both the natural products and a variety of analogs, has been achieved. The key step is the coupling reaction between a-pyrone-pyridine moiety (4) and the acid chloride of sesquiterpene moiety (3) in the presence of Lewis acid to construct ketone (2). The sesquiterpene moiety has been synthesized via stereoselective reductive formylation, palladium associated carbonylation, and allylic oxidation started from (+)-Wieland-Wiescher ketone.(+)-Pyripyropene E (15) also has been synthesized from farnesyl acetate(9 steps, 9.6 % overall yield). The convergent and stereoselective route exploited a biomimetic polyene cyclization as the key transformation.We also made over 300 derivatives usuing theses synthetis scheme, and clarified the structure-activity relationships.