Synthetic studies on Et-743. Assembly of the pentacyclic core and a formal total synthesis.
A formal total synthesis of the potent anticancer agent Et-743 is described. The tetrahydroisoquinoline core is stereoselectively constructed using a novel radical cyclization of a glyoxalimine. Further elaboration of this core rapidly accessed the pentacyclic core of Et-743, but a mixture of regiosisomers was obtained in the key Pictet-Spengler ring closure. A known advanced intermediate in the synthesis of Et-743 was intercepted, constituting a formal synthesis of the molecule.
Fishlock
Dan
D
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, USA.
Williams
Robert M
RM
D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis*; D004149:Dioxoles / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis*; D000077606:Trabectedin
D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D007202:Indicators and Reagents; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin