1257415-66-9Relevant academic research and scientific papers
Synthesis of (±)-phthalascidin 650 analogue: New synthetic route to (±)-phthalascidin 622
Razafindrabe, Christian R.,Aubry, Sylvain,Bourdon, Benjamin,Andriantsiferana, Marta,Pellet-Rostaing, Stéphane,Lemaire, Marc
experimental part, p. 9061 - 9066 (2011/01/04)
A synthesis of functionalized phenolic α-amino-alcohol (±)-13 as synthetic precursor of the catechol tetrahydroisoquinoline structure of phthalascidin 650 is disclosed. Starting from 3-methylcatechol 5, eight steps of synthesis give rise to the synthesis of phenolic α-amino-alcohol (±)-13 in 27% overall yield. This synthetic strategy involves the elaboration of fully functionalized aromatic aldehyde 8 and its transformation into a phenolic α-amino-alcohol (±)-13, through a Knoevenagel condensation, simultaneous reduction of nitroketene and ester functions and hydrogenolysis of the benzyl protecting group. The pentacycle (±)-18 was obtained after four additional steps. The Pictet-Spengler cyclisation between the phenolic α-amino-alcohol (±)-13 and N-protected α-amino-aldehyde 4 allowed to obtain (1,3′)-bis- tetrahydroisoquinoline 14 with N-methylated and N-Fmoc removed. The last step was a Swern oxidation for allowing an intramolecular condensation.
Synthesis of (±)-phthalascidin 622
Christian, R. Razafindrabe,Sylvain, Aubry,Benjamin, Bourdon,Marta, Andriantsiferana,Stephane, Pellet-Rostaing,Marc, Lemaire
experimental part, p. 1888 - 1898 (2011/02/26)
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.
