Regioselective quinazolinone-directed ortho lithiation of quinazolinoylquinoline: practical synthesis of naturally occurring human DNA topoisomerase I poison luotonin a and luotonins B and E.
A regioselective quinazolinone-directed ortho lithiation on an adjacent quinoline moiety has been used as a key step for a short, efficient, and practical synthesis of the human DNA topoisomerase I poison luotonin A and luotonins B and E. The quinazolinoylquinoline 5 on treatment with in situ-generated nonnucleophilic mesityllithium furnished the desired dilithiated intermediate 6, which on treatment with formaldehyde followed by Mitsunobu ring closure reaction gave luotonin A (1a) in very good yield. The reaction of dilithiated intermediate 6 with DMF directly furnished luotonin B (1b) in 81% yield. Luotonin B (1b) on methylation with p-TSA/methanol gave luotonin E (1c) in 82% yield.
Mhaske
Santosh B
SB
Combi Chem-Bio Resource Center, Division of Organic Chemistry (Synthesis), National Chemical Laboratory, Pune 411 008, India.
Argade
Narshinha P
NP
D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008094:Lithium / Q000737:chemistry*; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D011809:Quinones / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D059004:Topoisomerase I Inhibitors
D004791:Enzyme Inhibitors; D011758:Pyrroles; D011799:Quinazolines; D011809:Quinones; D059004:Topoisomerase I Inhibitors; C480761:luotonin A; C499206:luotonin B; C499205:luotonin E; D008094:Lithium