Enantioselective Total Synthesis of (−)-Zygadenine

Abstract

The Veratrum alkaloids are highly complex steroidal alkaloids characterized by their intricate structural and stereochemical features and exhibit a diverse range of pharmacological activities. A new synthetic pathway has been developed to access this family of natural products, which enabled the first total synthesis of (−)-zygadenine. This synthetic route entails the construction of a hexacyclic carbon skeleton through a stereoselective intramolecular Diels–Alder reaction, followed by a radical cyclization. Subsequently, a meticulously designed sequence of redox manipulations was optimized to achieve the de novo synthesis of this highly oxidized Veratrum alkaloid.

Thiourea-Mediated Stereospecific Deoxygenation of Cyanoepoxides to Access Highly Diastereopure Alkenyl Nitriles

“…Stereoenriched alkenyl nitriles are an important family of functionalized and highly polarized alkenes that have found prevalent applications in numerous fields. In synthetic and pharmaceutical chemistry, they were used as important synthetic intermediates and building blocks for total synthesis natural products, medicinally relevant compounds, and other multifunctionalized molecules . Additionally, alkenyl nitriles themselves are also biologically active compounds such as anticancer agents CC-5079, or serve as key component of some drug molecules such as anti-HIV agents rilpivirine and fosdevirine, as well as anticancer agents hemiphorboxazole A and calyculin A (Figure ).…”

Convergent and Efficient Total Synthesis of (+)-Heilonine Enabled by C–H Functionalizations

“…Due to the structural diversity, complexity, and therapeutic potential of the Veratrum steroidal alkaloids, they have attracted significant synthetic attention since the 1960s. , In 1967, the Masamune group and the Johnson group reported breakthrough total syntheses of jervine ( 6 ) in 47 steps and veratramine ( 8 ) in 41 steps, respectively. Both syntheses could be traced back to Hagemann’s ester.…”

Convergent Total Synthesis of (−)-Cyclopamine

“…The intricate structures of Veratrum alkaloids have piqued the interest of synthetic chemists for years . With respect to cyclopamine, the rare C- nor -D- homo steroid skeleton is further complicated by the fully substituted, spirocyclic THF motif, the unique trans -6,5-EF ring system, and the central tetrasubstituted olefin, all of which pose unique challenges to its synthesis.…”