Synthesis of an aspidosperma alkaloid precursor: synthesis of (+)-aspidospermidine

Synthesis of Aspidodispermine via Pericyclic Framework Reconstruction

“…When performing the Fischer indole reaction on 12 , the desired indolenine was indeed the major product confirming our initial hypothesis. Its stereoselective reduction with NaBH 4 and acetylation gave protected aspidodispermine 14 . At this point, the stereoconfiguration of the 5-acetoxy group could be verified through its unusual upfield shift (1.36 ppm), hinting at the acetoxy methyl to be orthogonally oriented toward the aromatic ring.…”

Synthetic Approaches to Tricyclic Aminoketones in the Total Synthesis of Aspidosperma and Kopsia Alkaloids

“…Among the aforementioned precursors, tricyclic lactams, including five‐ and six‐membered lactams, are the most common advanced intermediates for the synthesis of tricyclic aminoketones 1 . A total of 18 synthetic strategies were achieved to synthesize 1 via the construction of tricyclic lactams [10–23] . These tricyclic lactams are almost converted into 1 via a three‐step reaction sequence involving ketalization, reduction, and deketalization as first reported by Stork and Dolfini.…”

“…Later that same year, Gnecco and co‐workers also reported the asymmetric total synthesis of (+)‐aspidospermidine ((+)‐ 7 ) via chiral auxiliary‐controlled stereoselectivity (Scheme 9). [17] The authors focused on the asymmetric synthesis of ketone (−)‐ 20 a , which was reported by Stork and Dolfini. Beginning from the condensation reaction of 4‐formyl‐hexanoic acid methyl ester 16 with ( S )‐ α ‐methylbenzylamine followed by reduction of lactam with LiAlH 4 gave enamine 65 .…”

“…Therefore, this review will summarize the synthetic approaches to the tricyclic aminoketones 1 since 1963, including highlight the construction of the C‐/D‐/E‐ring with the all‐carbon quaternary stereogenic center, and subsequent give a brief introduction to complete the synthesis of aspidosperma and kopsia alkaloids. In addition, this review will discuss the formation of tricyclic aminoketones 1 based on their precursors, including tricyclic lactams, [10–23] tricyclic vinylogous amides, [24–28] tricyclic enones, [29–31] tricyclic ethers, [32] tricyclic ketals, [33] tricyclic esters, [34] and non‐tricyclic precursors [35–38] …”

Protecting-Group-Free Formal Synthesis of Aspidospermidine: Ring-Opening Cyclization of Spirocyclopropane with Amine Followed by Regioselective Alkylations

“…Recently, Jiang and co-workers demonstrated a divergent asymmetric synthesis of Aspidosperma alkaloids including (−)-pyrifolidine ( 1c ) and (+)-vincadifformine ( 1e ) from 2 . Therefore, intermediate 2 has become an attractive and well-known target as a Stork’s intermediate, and various synthetic approaches to 2 have been reported to date. , …”