Synthesis of (–)‐Cryptopleurine by Combining Gold(I) Catalysis with a Free Radical Cyclization

Abstract

(R)‐(–)‐Cryptopleurine, a highly cytotoxic alkaloid found in Cryptocarya and Boehmeria species, was synthesized in high optical purity using a gold(I)‐NHC catalyzed cyclization of an unsymmetrical phenanthrene precursor combined with a free radical cyclization to achieve closure of the C‐ring.

Gold‐Catalyzed Hydrofunctionalizations and Spiroketalizations of Alkynes as Key Steps in Total Synthesis

“…The generally observed high selectivity for the 6‐ endo over the 5‐exo pathway in these transformations is also observed in the case of internal alkynes as in the total synthesis of (−)‐Cryptopleurine . The coumarin natural products Pimpinellin, Fraxetin and (±)‐Purpurasol could nicely be accessed by a similar 6‐ endo ‐ dig hydroarylation reaction as well as the tetracyclic core of Berkelic acid …”

“…[13] The generally observed high selectivity for the 6-endo over the 5-exo pathway in these transformations is also observed in the case of internal alkynes as in the total synthesis [14] of (À)-Cryptopleurine. [15] The coumarin natural products Pimpinellin, Fraxetin and (AE)-Purpurasol could nicely be accessed by a similar 6-endo-dig hydroarylation reaction [16] as well as the tetracyclic core of Berkelic acid. [17] The akuammiline alkaloid (À)-Aspidophylline A was isolated from Malayan Kosia Singapurensis in 2007 and shows promising activity against human KB nasopharyngeal cancer cells.…”

The xanthate route to lactams

“…This route to dihydroisoquinolones was exploited by Opatz in a short synthesis of (-)cryptopleurine 214, the last steps of which are outlined in Scheme 47. 78 Thus, treatment of xanthate 212 with DLP induces cyclization into lactam 213 and reduction with lithium aluminum hydride provides the target molecule 214. . 81 Indeed, this molecule is an obvious choice for illustrating the power of xanthate chemistry.…”

Screening of Phenanthroquinolizidine Alkaloid Derivatives for Inducing Cell Death of L1210 Leukemia Cells with Negative and Positive P-glycoprotein Expression

“…A rich source of plant alkaloids with a wide range of biological activities is found in the Leguminosae family. Cryptopleurine, a phenanthroquinolizidine alkaloid, was isolated from Cryptocarya and Boehmeria species [5] as a compound with potent antiviral [6], anti-inflammatory [7] and antiproliferative activity [8,9]. It is representative of natural compounds with a common pentacyclic structure such that the phenanthrene ring is conjugated with quinolizidine.…”