Developments in the Synthesis of Hasubanan Alkaloids

Abstract

This review critically summarized the synthesis of hasubanan alkaloids with the focus on construction of hasubanan core. Historical and recent reports are systemized based on the strategic bonds formation and are given in comparison. Special accents are made on the achievements in collective syntheses, asymmetric syntheses, and biomimetic approaches. Based on the summarized data potential perspectives are highlighted.

Merging Johnson–Claisen and Aromatic Claisen [3,3]-Sigmatropic Rearrangements: Ytterbium Triflate/2,6-Di-tert-butylpyridine Catalytic System

“…Related cyclizations could be achieved by alkene oxidation: epoxidation with m CPBA and further treatment with p TsOH provided hydroxymethyl derivative 12 as 1:1 mixture of diastereomers (epimerization occurs on the last step); the Wacker-type cyclization, − in its turn, gave rise to benzofuran derivative 13 in 73% yield. Yet another cyclization was demonstrated on the 5-formyl derivative: phenolate methylation and further Wacker oxidation/aldol cyclization of protected phenol 14 produced naphthalene derivative 15 , which we plan to use later in the hasubanan total synthesis. − Given that the ozonolysis/Friedel–Crafts modification has been already exploited in total synthesis of Lepenine by Fukuyama, such substrates show great potential for further synthetic applications.…”

Recent asymmetric synthesis of natural products bearing an α-tertiary amine moiety via temporary chirality induction strategies

“…Hasubanan alkaloids are natural products mainly isolated from the Stephania genus. [112][113][114][115] Most of these alkaloids feature a benzannulated aza [4.4.3]propellane core and two contiguous tetrasubstituted stereocenters at the fused positions (Scheme 26). In 2019, Kim group reported the asymmetric synthesis of these alkaloids via MOC-assisted intramolecular alkyne carbocyclization of amino ester enolates onto an alkyne as a key step.…”