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 ...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.展开更多
文摘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.
