Catalytic Asymmetric Total Synthesis of Macrocyclic Marine Natural Product(-)-Haliclonin A  

作　　者：Shi-Peng Luo Xiong-Zhi Huang Lian-Dong Guo Pei-Qiang Huang 

机构地区：[1]Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province,College of Chemistry and Chemical Engineering,Xiamen University,Xiamen,Fujian 361005,China [2]School of Chemistry and Environmental Engineering,Jiangsu University of Technology,Changzhou,Jiangsu 213001,China

出　　处：《Chinese Journal of Chemistry》2020年第12期1723-1736,共14页中国化学（英文版）

基　　金：The authors are grateful for financial support from the National Natural Science Foundation of China(Grant Nos.21672176,21931010,and 21472153);the National Basic Research Program(973 Program)of Lhina(Grant No.2010CB833200);and the Program for Changjiang Scholars and Innovative Research Team inllniversity(PCSIRT)of Ministry of Education,ChinaMs.Yanliao Gao is thanked for assisting in the submission of this manuscript.

摘　　要：of main observation and conclusion We describe the full details of our total synthesis of haliclonin A,a macrocyclic natural product suggested to originate from a common biosynthetic intermediate as sarain A.Central to our synthetic route is the strategic employment of nitromethane for several purposes:(1)as an umpolung surrogate of an aminomethyl group;(2)as an ideal nucleophile for the highly enantioselective catalytic asymmetric conjugate addition to forge the challenging all-carbon quaternary stereogenic center that was used to induce the formations of all other chiral centers of the molecule;and(3)as a CiNi building block to form the 3-azabicyclo[3.3.1]nonane framework.The realization of this strategy relied on the development of a novel organocatalytic asymmetric conjugate addition of nitromethane to 3-alkenyl cyclohex-2-enone;and the first Pd-promoted intramolecular coupling of a thiocarbamate moiety onto an electron-deficient alkene(enone)to form the 3-azabicyclo[3,3,l]nonane core.The synthesis also features a Sml2-mediated intermolecular reductive coupling of an enone with an aldehyde,ring-closing alkene and alkyne metathesis reactions to build the two aza-macrocycles,and an unprecedented direct transformation of enol into enone.

关 键 词：CONJUGATE METHANE SYNTHESIS 

分 类 号：O62[理学—有机化学]