Total Synthesis of (±)‐Alstoscholarisine A

Abstract

The first total synthesis of the neuroactive indole alkaloid (±)-alstoscholarisine A is reported. The key step of the concise synthesis is an efficient domino sequence that was used to assemble the 2,8-diazabicyclo[3.3.1]nonane core through the formation of two C-N bonds and one C-C bond in a single step.

Total Syntheses of the Monoterpenoid Indole Alkaloids (±)‐Alstoscholarisine B and C

“…This lactol could be acylated with acetic anhydride to yield the lactol acetate 19 . It should be noted that a similar epimerization/cyclization sequence was used by Bihelovic and Ferjancic in their synthesis of alstoscholarisine A …”

“…A total synthesis of racemic alstoscholarisine A ( 1 ) was described in 2016 by Bihelovic and Ferjancic . In the same year, a synthesis of the natural (−)‐enantiomer of 1 was reported by Yang, et al .…”

“…Towards this end, the double bond of the allyl group in 13 was transposed through a thermal ene reaction with DEAD, leading to allylic hydrazine derivative 14 , which was produced exclusively as the E isomer in good yield. The desired aldehyde 15 could then be formed through dihydroxylation of alkene 14 , followed by cleavage with lead tetraacetate …”

Synthesis of two novel C-19 analogues of (±)-alstoscholarisine A

“…We have published a racemic synthesis of alstoscholarisine A (1) in 2016, in which the stereocenter at C-19 was formed in the last steps of the synthesis. 11 Therefore, it was decided to modify these last steps and to synthesize compounds 6 and 7, two new C-19 analogues of alstoscholarisine A (Scheme 1), in order to test whether a nonpolar, longer alkyl or an aryl substituent could alter the bioactivity. These two analogs could be accessible from the common lactonic intermediate 8 by the addition of the corresponding alkyl-or aryl-lithium reagent, followed by a subsequent stereoselective reduction of the intermediary hemiketal.…”

“…As a result, very elegant syn-936 BIHELOVIC, FERJANCIC and JONCEV theses of this intriguing molecule have been published so far, two racemic and two enantioselective syntheses. [11][12][13][14]…”