Synthesis of(±)-phthalascidin 622  

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

机构地区：[1]Laboratoire de Chimie des Produits Naturels et Biotechnologie(LPNB),Université d'Antananarivo,17 Cité Mahatazana-Ampandrianomby,101 Antananarivo [2]ICBMS,Institut de Chimie et Biochimie Moléculaires et Supramoléculaires,CNRS,UMR5246,Laboratoire de Catalyse et Synthèse Organique [3]ICSM,institut de Chimie Séparative de Marcoule,CNRS/CEA/UM2/ENSCM,UMR 5257,Laboratoire de Tri Ionique par des Systèmes Moléculaires auto-assemblés

出　　处：《Science China Chemistry》2010年第9期1888-1898,共11页中国科学（化学英文版）

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 sesamol.Starting from 3-methyl catechol 5,8 steps gave rise to the synthesis of phenolic α-amino-alcohol(±)-16 in 27% overall yield.This 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 group.The pentacycle(±)-4 was obtained after 4 additional steps.The 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 removed.The last step was a Swern oxidation allowing the expected intramolecular condensation.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 sesamol.Starting from 3-methyl catechol 5,8 steps gave rise to the synthesis of phenolic α-amino-alcohol(±)-16 in 27% overall yield.This 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 group.The pentacycle(±)-4 was obtained after 4 additional steps.The 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 removed.The last step was a Swern oxidation allowing the expected intramolecular condensation.

关 键 词：phthalascidin ecteinascidin (1 3’)-bis-tetrahydroisoquinoline PICTET-SPENGLER Bishler-Napieralsky 

分 类 号：O621.3[理学—有机化学]