Synthesis of(±)-phthalascidin 622

作     者：CHRISTIAN R.Razafindrabe SYLVAIN Aubry BENJAMIN Bourdon MARTA Andriantsiferana STEPHANE Pellet-Rostaing MARC Lemaire 

作者机构：Laboratoire de Chimie des Produits Naturels et Biotechnologie(LPNB)Université d'Antananarivo17 Cité Mahatazana-Ampandrianomby101 Antananarivo ICBMSInstitut de Chimie et Biochimie Moléculaires et SupramoléculairesCNRSUMR5246Laboratoire de Catalyse et Synthèse Organique ICSMinstitut de Chimie Séparative de MarcouleCNRS/CEA/UM2/ENSCMUMR 5257Laboratoire de Tri Ionique par des Systèmes Moléculaires auto-assemblés 

出 版 物：《Science China Chemistry》 (中国科学（化学英文版）)

年 卷 期：2010年第53卷第9期

页      面：1888-1898页

核心收录：

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 

基　　金：AUF Antananarivo Region Rhone-Alpes EGIDE Lyon 

主　　题：phthalascidin ecteinascidin (1 3’)-bis-tetrahydroisoquinoline Pictet-Spengler Bishler-Napieralsky 

摘      要：A synthesis of functionalized phenolic α-amino-alcohols(±)-8 and(±)-16 as synthetic precursors of the catechol tetrahydroisoquinoline structure of phthalascidin 650 was disclosed.(±)-8 was prepared in 5 steps from the commercially available *** from 3-methyl catechol 5,8 steps gave rise to the synthesis of phenolic α-amino-alcohol(±)-16 in 27% overall *** synthetic strategy involved the elaboration of fully functionalized aromatic aldehyde 13 and its transformation into a phenolic α-amino-alcohol(±)-16,through a Knoevenagel condensation,simultaneous reduction of nitroketene and ester functions,and hydrogenolysis of the benzyl protecting *** pentacycle(±)-4 was obtained after 4 additional *** Pictet-Spengler cyclisation between the phenolic α-amino-alcohol(±)-16 and the N-protected α-amino-aldehyde 4 allowed to obtain(1,3 )-bis-tetrahydroisoquinoline 17 with N-methylated and N-Fmoc *** last step was a Swern oxidation allowing the expected intramolecular condensation.