The structures of talatisamine and cammaconine by correlation with isotalatizidine

Alkaloids of Aconitumcolumbianum Nutt•

“…It could be rccrystallized from acetone-hcxane or methanol giving prisms with mp 142-143°C. In an evacuated capillary it had mp 148°C and showed no mp depression with a sample with mp 148.5"C (cvacuated capillary) obtained from S. Yu 14-DeI1j~drortrlutisr11~1irre (7) Twenty-five mg of chromium trioxide was added to a stirred solution of 85 nig of talatisamine in I mL of acetic acid. After 4 11 at room temperature the solution was evaporatcd under rcduccd pressure.…”

A partial synthesis of aconosine

“…14-Dehydrooxocnmrnnco~~ic acid 6 The mixture of acids from permanganate oxidation of oxocammaconine (370 mg) was dissolved in 20 mL of acetone, thcn Jones' reagent (14) diluted with acetone was added with stirring until an excess persisted for 10 min. Excess reagent was destroyed with methanol, the solids removed by decantation and filtration.…”

“…then the solvent evaporated. The residue yielded 361 mg of acids which crystallized from aqueous acetone giving 176 mg (36% from oxocammaconine) of 14-dehydrooxocammaconic acid (6 Lithium aluminum hydride (I70 mg) was added to a solution of 100 mg of oxoaconosine (8) in 5 mL of dioxanc. The mixture was refluxed for 2 h under argon.…”

Total Synthesis of Talatisamine

“…Total synthesis of talatisamine (1). Reagents and conditions:a )Me 2 PhSiCl, Li, Et 2 Zn, THF, À78 8 8C, 91 %; b) NaH, KH, (MeO) 2 CO, THF, reflux;c)LiN(i-Pr) 2 ,H MPA, MeOCOCN,THF, À78 8 8Cto08 8C; d) HCHO aq.,EtNH 2 aq.,MeOH, 0 8 8CtoRT, 43 %(3steps, a-R 2 :b-R 2 = 1:2.5); e) HBF 4 ·OEt 2 ,1 ,2-dichloroethane, 4:1);m )NaN(TMS) 2 ,MeI, THF, 0 8 8C, 49 %( 3steps);n )nBu 4 NF, THF, 60 8 8C; o) NaH, MeI, DMF, 0 8 8CtoRT, 86 %( 2steps);p)DIBAL-H, CH 2 Cl 2 , À50 8 8C; q) Dess-Martin periodinane, CH 2 Cl 2 ,7 3% (2 steps);r)B,t oluene,T HF, 0 8 8Ct oRT; s) BF 3 ·OEt 2 ,Me 2 S, CH 2 Cl 2 , À40 8 8C, 78 %(2steps);t)HBr aq.,D MSO, EtOAc, 60 8 8C; NaBH(OAc) 3 Then ext coupling between AE-ring 7 and D-ring 6 [23] required installing the tetrasubstituted C5-carbon center at the double neopentyl position without damaging the two methoxy carbonyl groups (Scheme 2). This demanding task was realized by derivatizing 6 (1.7 equiv) to the corresponding alkynyl magnesium bromide and subsequent chemoselective addition to the C5-carbonyl group at 0 8 8Ci nT HF,t hereby producing 15 in 85 %y ield (a-R 3 :b-R 3 = 1:1).…”

“…[1] Many of these alkaloids modulate ion channels [2] and display ar ange of biological properties, including anti-inflammatory,a nalgesic,a ntiarrhythmic,a ntipyretic,antiepileptic,hypotensive,and bradycardic activities. Talatisamine (1), isolated from an Aconitum species,w as structurally determined to be ah ighly oxygenated C 19 diterpenoid alkaloid [3,4] that selectively inhibits K + channels and shows an antiarrhythmic effect. [5] Although the C 18diterpenoid alkaloids lack aC 4-substituent (as in, e.g., neofinaconitine,w eisaconitine D), all C 18 -a nd C 19 -alkaloids share the same hexacyclic 6/7/5/6/6/5-membered-ring framework (ABCDEF-ring).…”