Biogenetically inspired approach to the Strychnos alkaloids. Concise syntheses of (+/-)-akuammicine and (+/-)-strychnine.
A linear synthesis of the indole alkaloid (+/-)-akuammicine (2) was completed by a novel sequence of reactions requiring only 10 steps from commercially available starting materials. The approach features a tandem vinylogous Mannich addition and an intramolecular hetero Diels-Alder reaction to rapidly assemble the pentacyclic heteroyohimboid derivative 8 from the readily available hydrocarboline 6. Oxidation of the E ring of 8 gave the lactone 9 that was converted into deformylgeissoschizine (11). The subsequent elaboration of 11 into 2 was effected by a biomimetically patterned transformation that involved sequential oxidation and base-induced skeletal reorganization. A variation of these tactics was then applied to the synthesis of the C(18) hydroxylated akuammicine derivative 36. Because 36 had previously been converted into strychnine (1) in four steps, its preparation constitutes a concise, formal synthesis of this complex alkaloid.
Ito
M
M
Department of Chemistry and Biochemistry, The University of Texas, Austin, Texas 78712, USA.
Clark
C W
CW
Mortimore
M
M
Goh
J B
JB
Martin
S F
SF
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry; D003500:Cyclization; D026121:Indole Alkaloids; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010946:Plants, Medicinal / Q000737:chemistry*; D012639:Seeds / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D013331:Strychnine / Q000138:chemical synthesis* / Q000737:chemistry
C434143:2,16,19,20-tetradehydro-18-hydroxycuran-17-oic acid, methyl ester; D000470:Alkaloids; D002243:Carbolines; D026121:Indole Alkaloids; D007211:Indoles; C410326:geissoschizine; D013331:Strychnine; C434103:akuammicine