Origination of functional chiral building blocks using asymmetric acylation and application to the synthesis of biologically active compounds

目前，酶被认为是不对称合成的底物专一性和高对映选择性催化剂。特别是在有机溶剂作为反应介质的基础上，脂肪酶最近被用于生物催化拆分，我们成功地实现了固定化脂肪酶介导的N，N-二烷基-3-羟基-4-戊烯胺的拆分，但Katsuki-Sharless不对称环氧化拆分失败。所制备的均手性内酯的碘内酯化反应和O-保护的同手性内酰胺的氧内酯化反应是立体选择性的，分别得到顺式-3，4-双取代伽马内酯的两个对映体和反式-3，4-二取代的反式-3，4-内酯的两个对映体。这些伽马内酯已被用作手性构建块，用于合成生物活性化合物，如木犀草内酯、(+)-blastimycinone、NFX-2、NFX-4、柳珊瑚代谢产物和麝香碱以顺式-3，4-二取代伽马-内酯为掩蔽的丁烯内酯手性配体，合成了(+)-反式-威斯基和(+)-反式干邑内酯、(-)-亚甲基内酯、(+)-肾甾烷酸和(+)-岩藻酸，并将这些伽马-内酯作为手性碳五组分用于合成昆虫信息素。

Enzymes are now recognized as substrate-specific and highly enantioselective catalyst for asymmetric synthesis. In particular, lipases have recently been used for biocatalytic resolutions on the basis of the admission of organic solvents as reaction media.We succeeded immobilized lipase-mediated resolution of N,N-dialky1-3-hydroxy-4-pentenamides, unsuccessful in resolution by the Katsuki-Sharpless asymmetric epoxidation. Iodolactonizaion of thus prepared homochiral amides and oxy-lactonization of O-protected homochiral amides proceeded stereoselectively, affording both enantiomers of cis-3,4-disubstituted gamma-lactone and both enantiomers of trans-3,4, disubstituted gamma-lactone preferentially, respectively.These gamma-lactones have been used as chiral building blocks for the synthesis of biological active compounds such as litsenolides, (+) -blastimycinone, NFX-2, NFX-4, metabolites from Gorgonian Plexaura flava, and muscarine.Especially, cis-3,4-disubstituted gamma-lactones were served as the masked butenolide chirons and a concise synthesis of (+) -trans-wisky and (+) -trans-cognac lactones, (-) -methylenolactocin, (+) -nephrosteranic acid, and (+) -roccellaric acid has been achieved.In addition, these gamma-lactones have been apllied as chiral carbon five building blocks for the synthesis of insect pheromons.