Chemical Studies of alpha-Pyrone Meroterpenoids

首次全合成了微生物α-吡喃酮部分萜类化合物，（+）-啶南平A（1），酰基-CoA：胆固醇酰基转移酶（ACAT）抑制剂，这是一种有效和简洁的收敛方法（14步，9.3%产率），旨在提供容易获得的天然产物和各种类似物。关键步骤是α-吡喃酮-吡啶部分（4）与倍半萜烯部分（3）的酰氯在刘易斯酸存在下发生偶联反应，生成酮（2）。以（+）-Wieland-Wiescher酮为起始原料，通过立体选择性还原缩合、钯相关羰基化和烯丙基氧化反应合成了倍半萜部分。（+）-啶南平E（15）也由乙酸法呢酯合成（9步，9.6%总产率）。该合成路线以仿生多烯环化反应为关键，采用收敛性和立体选择性的方法，合成了300多个衍生物，并阐明了构效关系。

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.