Total Syntheses of (+)‐Villocarine A, (−)‐Apogeissoschizine, and (+)‐Geissoschizine

Abstract

Total syntheses of geissoschizine‐type monoterpenoid indole alkaloids (MTIAs) are reported. An intramolecular Pictet‐Spengler cyclization was developed for the selective construction of the 3R stereocenter. The first total synthesis of (+)‐villocarine A was then achieved. Furthermore, the first total synthesis of the highly strained (−)‐apogeissoschizine was also accomplished in an aza‐Michael cyclization/E1cB elimination/stereoselective olefin isomerization sequence. Finally, (+)‐geissoschizine, a common biosynthetic intermediate of MTIAs, was obtained from apogeissoschizine through ring‐opening along with a release of ring strain.

Collective Total Synthesis of β-Carboline-Type Monoterpenoid Indole Alkaloid Glycosides

“…In our previous synthesis of MTIAs, we succeeded in the selective hydrolysis of the methyl ester in secologanin aglycone using the participation of the hydrated form of the aldehyde, which positions a hydroxyl group 6-atoms away from the ester carbonyl carbon. 16 Therefore, this unique intramolecular hydration reaction was employed to differentiate the methyl ester from the acetyl groups. Thus, when secologanin tetraacetate ( 12 ) was treated with 15 equiv of triethylamine, a weak base, in an aqueous acetonitrile solution at room temperature, the hydrated product 17 was afforded in excellent yield (6 h, 91%).…”

Bioinspired Total Syntheses of Secologanin-Related Natural Products: A Demonstration of the Power of Secologanin in the Flask

“…7a For the synthesis of MTIAs without a sugar chain, we also synthesized secologanin aglycone silyl ether 23 by introducing a tert -butyldimethylsilyl (TBS) group instead of d -glucose into hemiacetal 19 , followed by construction of the aldehyde and terminal olefin (Scheme 2b ). 8b…”

“…Indeed, we have successfully synthesized 19 MTIAs to date from this key intermediate 41 (or derivatives with slight modifications). 8b d f In this Account, we describe three of these synthetic pathways.…”

“…Finally, geissoschizine ( 10 ), 28 one of the important biosynthetic intermediates of MTIAs, was obtained from 51 via an aqueous HCl-induced ring-opening reaction that released ring strain. 8f 27…”

“…22 23 In this total synthesis, the removal of the silyl group triggered a complex bioinspired cascade reaction to build a unique natural product scaffold. 8b…”