Biomimetic Total Syntheses of Clavine Alkaloids

Abstract

Biomimetic total syntheses of either enantiomers of a number of ergot alkaloids, chanoclavine I (1b), chanoclavine I aldehyde (1c), pyroclavine (1e), festuclavine (1f), pibocin A (1g), 9-deacetoxyfumigaclavine C (1h), and fumigaclavine G (1i), have been achieved from seco-agroclavine (1a). The advanced intermediate for seco-agroclavine (1a) was synthesized via a key thiourea-catalyzed intramolecular nitronate addition onto α,β-unsaturated ester.

Synthesis of 3,4-Fused Tricyclic Indoles through Cascade Carbopalladation and C–H Amination: Development and Total Synthesis of Rucaparib

“…3,4-Fused tricyclic indoles are essential core structures of many bioactive natural products and pharmaceuticals and are attractive synthetic targets in the fields of medicinal chemistry and organic synthesis (Figure ) The synthesis of these complex indole molecules is challenging and has been the subject of numerous synthetic studies . Traditionally, 3,4-fused tricyclic indoles can be synthesized by the intramolecular cyclization of 4-substituted or 3,4-disubstituted indoles.…”

Synthetic Methods for 3,4‐Fused Tricyclic Indoles via Indole Ring Formation

“…Bisai et al. recently achieved a collective total synthesis of clavine alkaloids using a strategy based on an intramolecular organocatalytic asymmetric Michael addition of nitroalkane with 1 as a substrate [Scheme (a)] . Intramolecular amide condensation with azide derivative 3 was utilized as a key step in Kan and Fukuyama's total synthesis of decursivine [Scheme (b)] .…”

Recent Advances in Total Synthesis of Alkaloids from α,β‐Unsaturated Aldehydes

“…[33] Significant successes have also been achieved in the total synthesis of indole-containing alkaloids from α,β-unsaturated aldehydes. [34][35][36][37][38][39][40][41][42][43][44][45][46] It should be emphasized that MacMillan's group pioneered catalytic asymmetric indole dearomatization strategies and applied it in the total synthesis of a number of alkaloids 42-48 with high efficiency and selectivity ( Figure 3). [34a-c] Their original sequence based on intermolecular [4 + 2]cycloaddition (Scheme 7).…”

“…Bisai and co-workers demonstrated one-pot synthetic method for biomimetic total syntheses of tetracyclic clavine alkaloids, namely festuclavine (94) and pyroclavine (95) from chanoclavine I aldehyde (93) (Scheme 12). [43] The author started from the multi-stage construction of the chanoclavine I aldehyde, bearing a tricyclic substituent in position 3 (93). Then reaction in three-pot manipulations from enal 93 (hydrogenation, iminium-enamine tautomerization, reduction by NaBH 4 ) led to diastereomeric mixture of festuclavine (94) and pyroclavine (95) in 1.6 : 1 ratio.…”