New Perspectives in the Chemistry of Marine Pyridoacridine Alkaloids

Abstract

Secondary metabolites from marine organisms are a rich source of novel leads for drug development. Among these natural products, polycyclic aromatic alkaloids of the pyridoacridine type have attracted the highest attention as lead compounds for the development of novel anti-cancer and anti-infective drugs. Numerous sophisticated total syntheses of pyridoacridine alkaloids have been worked out, and many of them have also been extended to the synthesis of libraries of analogues of the alkaloids. This review summarizes the progress in the chemistry of pyridoacridine alkaloids that was made in the last one-and-a-half decades.

Pyridoacridines in the 21st Century

“…Electrophilic substitution of 3 with 4‐nitrophenyldiazonium fluoroborate allows later introduction of an amine function by reduction and thence by condensation with 1,10‐phenanthroline‐5,6‐dione, formation of octacyclic analogue 5 of eilatin (Scheme ) (for structure of eilatin see Figure )…”

“…[10] ple, ethacridine 1 was transformed into chloro compound 2 and this into the 2,2-dimethoxyethanamine 3, acid-catalysed closure of which produced (Scheme 1) a pyrido[4,3,2-kl]acridine 4. [10] Electrophilic substitution of 3 with 4-nitrophenyldiazonium fluoroborate allows later introduction of an amine function by reduction and thence by condensation with 1,10-phenanthroline-5,6-dione, formation of octacyclic analogue 5 of eilatin (Scheme 1) [9] (for structure of eilatin see Figure 4) Alkylpyrido[4,3,2-kl]acridines 7 were prepared [11,12] using the previously described synthetic procedure . [13] The synthesis starts with a cycloaddition of dimethylaminoprop-2-yne (or 5chloropent-1-yne) to 9-azidoacridine to give a regioisomeric mixture of triazolylacridines 6a and 6b (or 6c and 6d) (Scheme 2).…”

“…We earlier summarised synthetic routes to pyridoacridines . More recently, the following relevant aspects have been considered: “ ortho ‐Directed metallation of π‐deficient heterocycles in connection with palladium‐catalyzed biaryl cross‐coupling – synthesis of marine alkaloids of the pyridoacridine series”, “Marine pyridoacridine alkaloids and synthetic analogues as antitumor agents”, “Biological activities of pyridoacridines” “A mini review on pyridoacridines: prospective lead compounds in medicinal chemistry”, “Alkaloids from marine invertebrates as important leads for anticancer drugs discovery and development”, “Marine pyridoacridine alkaloids: biosynthesis and biological activities”, and “New perspectives in the chemistry of marine pyridoacridine alkaloids” …”

“…discovery and development", [7] "Marine pyridoacridine alkaloids: biosynthesis and biological activities", [8] and "New perspectives in the chemistry of marine pyridoacridine alkaloids". [9] In this review we consider all of the fifteen isomers, including natural product chemistry and synthesis reported in the 21 st century. Each isomer is named as a "pyrido[A,B-yz]acridine" to emphasise the isomeric relationship, but where this name is not the systematic name, the Chemical Abstracts name is given in {brackets}.…”

Ascidian Toxins with Potential for Drug Development

“…Meridine ( Figure 6 ) docking was predicted to be the most favorable, although these studies will need to be followed up experimentally. A recent review summarizes the progress that has been made in the synthetic chemistry of the pyridoacridine alkaloids [ 106 ].…”