Biosynthetic Relationships and Total Syntheses of Naturally Occurring Benzo[c]Phenanthridine Alkaloids

Abstract

Benzo[c]phenanthridine alkaloids sharing a tetracyclic structural motif, are an important class of nitrogencontaining small molecules and are used for the treatment of a number of diseases. This review presents a comprehensive survey of the occurrence, chemistry, biochemistry, and biological activity of benzophenanthridine alkaloids. Synthetic approaches to a number of benzo[c]phenanthridine are disclosed in this Minireview. Biosynthetic Relationship of Tetrahydroisoquinoline and Benzo[c]phenanthridine AlkaloidsA plausible biogenetic connection between tetrahydroisoquinoline and benzo[c]phenanthridine alkaloids is shown in Scheme 1. Protopine (3 a) can undergo a demethylation followed by reductive amination to generate tetrahydroisoquinoline alkaloid, stylopine (2 a). The latter can further undergo an [a] Dr. oxidative CÀ N bond cleavage leading to intermediate aldehyde 4 a, which can form a new CÀ C bond (see, 4 c) assisted by in-situ prepared enamine. An elimination followed by oxidation leads to the synthesis of norsanguinarine (1 a).

An Update of the Sanguinarine and Benzophenanthridine Alkaloids’ Biosynthesis and Their Applications

“…These activities rely on their structural features. Structural requirements for activity include planar configuration, N methyl substitutions, hydroxylation patterns, and the fusion of the B/C ring [2,3,57].…”

“…Sanguinarine (I), chelerythrine (III), and their direct dihydro derivatives are the most studied alkaloids among BZD. However, other minor compounds also display similar physiological activities, although with wide variations in their effective doses [2,3]. Table 3 shows some of the main BZD alkaloids with their ascribed pharmacological activity and the biochemical mechanisms involved.…”

“…Finally, BDZ type III results from the N protonation of BDZ type I or II, leading to the corresponding ammonium quaternary salts (Figure 1) [2,3]. Depending on the chemical modifications within these basic structures, up to seven groups can be distinguished: hexahydrobenzophenanthridines (type I), seco-benzophenanthridines (type II-1), dimeric dihydrobenzophenanthridines (type II-2), N-demethylbenzophenanthridines, dihydrobenzophenanthridines, benzophenanthridones, and quaternary benzophenanthridine alkaloids (type III; Figure 1) [2,3]. Plants bearing BDZ have had important roles in human traditional medicine in both the old and new world cultures for centuries.…”

Prodrug Activation by Gold Artificial Metalloenzyme‐Catalyzed Synthesis of Phenanthridinium Derivatives via Hydroamination

“…The prodrug strategy not only can generate 5‐methyl phenanthridinium derivatives to mimic naturally occurring alkaloids bearing a 5‐methyl phenanthridinium core (i.e. sanguinarine), [19] but can also synthesize quaternary ammonium cation compounds. Nitrogen heteroaromatic cations are interesting due to their reactivity and biological properties [20] .…”

Hantzsch Ester‐Mediated Synthesis of Phenanthridines under Visible‐Light Irradiation

“…The phenanthridine scaffold is one of the most remarkable ones among the large family of aza-heterocycles owing to its presence in natural as well as synthetic molecules of medicinal, agricultural and industrial importance. [1] The phenanthridine containing molecules exhibit diverse biological activities such as antibacterial, anticancer, antimalarial, antifungal, antiviral, cytotoxic etc. [2] The phenanthridine motif possess unique photophysical properties and finds use in luminescent materials, liquid crystals, and nanomaterials etc.…”