Jia Junhao, Wang Yue, Zhou Qin, Chen Ruijiao, Chen Xiaochuan
Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, PR China.
Jining Medical College, Jining 272067, PR China.
J Org Chem. 2023 Aug 4;88(15):10905-10915. doi: 10.1021/acs.joc.3c00931. Epub 2023 Jul 18.
A formal total synthesis of ecteinascidin 743 and lurbinectedin is achieved. Key features involve a Pictet-Spengler cyclization coupling of the tetrahydroisoquinoline and phenylalaninol moieties prepared by a common route with high yield and selectivity, a Parikh-Doering oxidation with good chemoselectivity and functionality tolerance, and a light-mediated A-ring elaboration of pentacyclic methoxyquinone substrates. By the approach, the known advanced intermediate (4-step conversion to Et-743) can be obtained conveniently in 21 total steps from -Cbz-l-tyrosine.
