Recent Advances Towards Syntheses of Diterpenoid Alkaloids

Abstract

The diterpenoid alkaloids serve as a rich source of synthetic targets for organic chemists, due to the intriguing structure of the overlapping ring systems, along with biological activities commonly associated with compounds of this group. Fifteen total syntheses and numerous synthetic studies towards construction of ring fragments have been reported since 2010. This review article gives a brief overview of diterpenoid alkaloids and summarizes the recent synthetic efforts.1 Introduction1.1 Structural Classification and Biosynthetic Origin1.2 Structure Elucidation of the Aconitum Alkaloids2 Total Syntheses2.1 C18-Diterpenoid Alkaloids2.2 C19-Diterpenoid Alkaloids2.3 C20-Diterpenoid Alkaloids3 Strategies To Synthesize Ring Systems3.1 Radical-Based Cyclizations3.2 Ruthenium-Mediated Enyne Cycloisomerization3.3 Reductive Coupling3.4 Diels–Alder Reactions3.5 Oxidative Dearomatization/Diels–Alder Sequence3.6 Transannular Aziridation3.7 Intramolecular [5+2] Cycloaddition3.8 Miscellaneous4 Conclusion

Functional identification of the terpene synthase family involved in diterpenoid alkaloids biosynthesis in Aconitum carmichaelii

“…The AcTPSs found in the TPS-c and TPS-e/f subfamilies cluster together, analogous to the diTPS found in T. wilfordii 25 , indicating a recent evolutionary event may responsible to the emergence of different classes of diterpene scaffolds. All of the class II diTPS genes proved to be ent -CPP synthase, which is accord with the common view that ent -CPP is the only intermediate involved in A. carmichaelii DAs biosynthesis 10 . Notably, AcCPS1 is specifically expressed in the fibrous root, as verified by RNA-seq and qPCR analysis, raising interesting questions about its function that necessitate further study.…”

“…1 C), which then undergo further development leading to the terminus C 18 - or C 19 -DAs. Historically, the specific enzymes and biosynthetic pathways in the plant have garnered substantially less interest than the total synthesis of these compounds: from 1963 to 2018, 24 different DAs have identified via total synthesis 10 . One of the few key mechanistic finding has been that l -serine may serve as the nitrogen source of atisine-type DAs 11 .…”

Iridium Acylnitrenoid-Initiated Biomimetic Cascade Cyclizations: Stereodefined Access to Polycyclic δ-Lactams

“…Realizing this limitation and lack of utility for ring-fused heterocyclic compounds, we envisioned that engineering a cascade cyclization process in which a heteroatom may be introduced into the core skeleton of cyclic products would provide a new opportunity to delve into chemically more diverse heterocyclic structures. In particular, we were motivated by the fact that ring-fused azacycles are an important building block for the synthesis of natural products, pharmaceutical agents, and molecular materials (Scheme a) …”

Stereoselective Synthesis and Antiproliferative Activity of Steviol-Based Diterpen Aminodiols

“…Although monoterpene-based 3-amino-1,2-diols are well-known compounds, their sesquiterpene or diterpene analogues are still not known in the literature. This is despite the fact that dihydroxy-substituted diterpene alkaloids as formal aminodiols with diverse pharmacological activity, owing to both basic nitrogen incorporated into their ring system and separated hydroxyl groups, have been thoroughly studied [22,23]. From this point of view, steviol, the aglycon of natural artificial sweetener stevisoide (isolated from the extract of the Paraguayan shrub Stevia rebaudiana L.) [24], has proved to be excellent starting material for the synthesis of ent-kaurane diterpenoids [25], with a wide range of biological activity (Figure 1), such as cytotoxic and apopthosis (I-III) [26][27][28][29], or glutathione S-transferase-inducing activity [30].…”