Enantiospecific total synthesis of indole alkaloids (+)-eburnamonine, (−)-aspidospermidine and (−)-quebrachamine

Simple indole alkaloids and those with a nonrearranged monoterpenoid unit

“…(+)-Eburnamonine (857) was derived from 860, and (À)-858 was synthesized starting with 859 through the Pictet-Spengler reaction and reductive ring opening of the quaternary salt (Scheme 178). 271,272 g-Pyrone-containing indole alkaloid pleiomaltinine (862) was derived from the natural alkaloid pleiocarpamine. The key Scheme 163 Reagents and conditions: (i) CH 2 ]CHMgBr, CuI, À70 C to À20 C; (ii) LiEt 3 BH, THF, 0 C: (iii) Ph 3 P, I 2 , imidazole, THF, rt; (iv) Zn, ethyl 2-(bromomethyl)acrylate, CuCN, TMSCl, 1,2-dibromoethane, DMF; (v) Grubbs' 2 nd generation catalyst, toluene, 80 C; (vi) POCl 3 , toluene, 80 C; (vii) NaBH 4 , EtOH, 0 C; (viii) TFA, CH 2 Cl 2 , rt.…”

Concise and Enantioselective Total Synthesis of (−)‐Mehranine, (−)‐Methylenebismehranine, and Related Aspidosperma Alkaloids

“…[1] In addition to (−)-aspidospermidine ( 1 ), [2] the archetype of this family of natural products with only the unfunctionalized pentacyclic core structure, several members with oxidation at C6 and C7 positions are known (Figure 1). (−)-Mehranine ( 2 ) was first isolated from Tabernaemontana divarica in 1995, but it was also found in Tabernaemontana bovina together with its hydrated congener (+)-(6 S , 7 S )-dihydroxy- N -methylaspidospermidine ( 3 ) in 1998.…”

“…[3] Moreover, the intriguing (−)- mehranine-derived dimers (−)-methylenebismehranine ( 4 ) and (+)-tabernaebovine ( 5 ) were also isolated from Tabernaemontana bovina , which possess connectivities through a methylene bridge at both C15 atoms and a direct C2–C15′ bond between two (−)-mehranine monomers, respectively. [4] While aspidospermidine ( 1 ) has served as a classic target for application of new synthetic methodologies, [2] no total synthesis of the oxidized monomers (−)- 2 and (+)- 3 or the dimers (−)- 4 and (+)- 5 has been reported to date. [5] Herein, we present the first total synthesis of (−)-mehranine ( 2 ) and (−)-methylenebismehranine ( 4 ) as well as access to (+)-(6 S ,7 S )-dihydroxy- N -methylaspidospermidine ( 3 ) and (−)-aspidospermidine ( 1 ), based on a highly diastereoselective transannular cyclization.…”

“…[2d,g,i, 8 ] We envisioned nine-membered lactam (+)- 13 , accessible from acyclic amino acid (+)- 12 in two steps (Scheme 2), as a suitable cyclization precursor. The rigid conformation of lactam (+)- 13 ensures a high level of diastereoselection and a more efficient spirocyclization step to pentacycle (−)- 17 via the diiminium intermediate 14 (Schemes 3 and 4).…”

“…[2af]: [α] 24 D =−17.4 (c = 0.32, MeOH)). The reaction proceeded in 84% yield in the presence of Adam’s catalyst, and the characterization data of alkaloid (−)- 1 matched previously reported data.…”