Enantioselective total synthesis of (+)-arborescidine C and related tetracyclic indole alkaloids using organocatalysis

Abstract

A concise and enantioselective synthesis of the tetracyclic indoles, including the naturally occurring compounds (+)-arborescidine C and (+)-arborescidine B, was achieved by the key step of Pictet-Spengler cyclization reaction with a Jacobsen-type thiourea organocatalyst. The synthetic process was further demonstrated in a pot-economy strategy and was achieved in a one-pot operation.

Marine natural products

“…Further work is required to clarify these ndings. The structures of a number of NPs have been conrmed by total synthesis including halocyamine A, 664 biselides A 665 and E, 666 ningalin G, 667 (+)-arborescidine C, 668 and (À)-pseudodistomin E. 669 Absolute conguration was assigned to the phosphorylated polyketide phospoeleganin (Sidnyum elegans) by synthesis of model fragment alicyclic compounds and their cyclic derivatives, and comparison of 1 H and 13 C NMR chemical shis. 670 Improved semisyntheses of ecteinascidin 743 and (À)-jorumycin from safracin B have been reported.…”

Recent Applications of Asymmetric Organocatalytic Methods in Total Synthesis

“…[70] In 2019, Hong and co-workers reported enantioselective total synthesis of (+)-arborescidine C (356, Scheme 38). [71] The synthesis started from tryptamine 350 and aldehyde 351, which underwent an organocatalytic enantioselective acyl-Pictet-Spengler reaction under the catalysis of a Jacobsen-type thiourea organocatalyst (352). The reaction led to the formation of the tricyclic product 353, which served as the key intermediate for the total synthesis (Scheme 38).…”

“…[71] Further elaborations of this product afforded (+)-arborescidine C (356) through a multistep sequence that included amide reduction with LiH 2 NBH 3 , reductive amination and cyclization reaction, and elimination reaction (Scheme 38). [71] In 2020, Brown and co-workers reported an enantioselective synthesis of (À )-cajanusine (365, Scheme 39). [72] The asymmetric intramolecular [ served as the key intermediate of the total synthesis.…”

“…The reaction led to the formation of the tricyclic product 353, which served as the key intermediate for the total synthesis (Scheme 38). [71] Further elaborations of this product afforded (+)-arborescidine C (356) through a multistep sequence that included amide reduction with LiH 2 NBH 3 , reductive amination and cyclization reaction, and elimination reaction (Scheme 38). [71] In 2020, Brown and co-workers reported an enantioselective synthesis of (À )-cajanusine (365, Scheme 39).…”

Pot Economy in the Total Synthesis of Estradiol Methyl Ether by Using an Organocatalyst

“…Based on this concept, we have reported a 60 minute one‐pot synthesis of (−)‐oseltamivir, one‐pot syntheses of ABT‐341 and Baclofen, and three‐pot synthesis of PGE 1 methyl ester . Cermizine B, epoxyisoprostanes, and arborescidine C have also been synthesized efficiently in a pot‐economical approach by other groups.…”