https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

Multicomponent reactions (MCRs) are fundamentally different from two-component reactions in several aspects. Among the MCRs, those with isocyanides have developed into popular organic-chemical reactions in the pharmaceutical industry for the preparation of compound libraries of low-molecular druglike compounds. With a small set of starting materials, very large libraries can be built up within a short time, which can then be used for research on medicinal substances. Due to the intensive research of the last few years, many new backbone types have become accessible. MCRs are also increasingly being employed in the total synthesis of natural products. MCRs and especially MCRs with isocyanides offer many opportunities to attain new reactions and basic structures. However, this requires that the chemist learns the “language” of MCRs, something that this review wishes to stimulate.

Multicomponent Reactions with Isocyanides.

Synthesis of oxygen- and nitrogen-containing heterocycles by ring-closing metathesis.

Drug discovery from marine natural products has enjoyed a renaissance in the past few years. Ziconotide (Prialt; Elan Pharmaceuticals), a peptide originally discovered in a tropical cone snail, was the first marine-derived compound to be approved in the United States in December 2004 for the treatment of pain. Then, in October 2007, trabectedin (Yondelis; PharmaMar) became the first marine anticancer drug to be approved in the European Union. Here, we review the history of drug discovery from marine natural products, and by describing selected examples, we examine the factors that contribute to new discoveries and the difficulties associated with translating marine-derived compounds into clinical trials. Providing an outlook into the future, we also examine the advances that may further expand the promise of drugs from the sea.

Drug development from marine natural products

Natural products to drugs: natural product derived compounds in clinical trials

Palytoxin has been isolated from the zoanthids "limu-make-o-Hana" (Tentatively identified as Palythoa sp.) as a noncrystalline, chromatographically pure entity. Apart from polypeptide and protein toxins, it is the most highly toxic substance known, with a lethal dose (LD 59 ) in mice of 0.15 microgram per kilogram by intravenous injection. Unlike the potent toxins batrachotoxin, saxitoxin, and tetrodotoxin which have molecular weights of 500 or less, palytoxin has an estimated molecular weight of 3300 and contains no repetitive amino acid or sugar units.

https://science.sciencemag.org/content/sci/172/3982/495.full.pdf

Palytoxin: a new marine toxin from a coelenterate.

Ciguatoxin, the agent responsible for ciguatera, a disease produced in humans from ingestion of certain fishes, has been isolated from specimens of the moray eel, Gymnothorax javanicus. The toxin is apparently a lipid containing quaternary nitrogen, hydroxyl, and carbonyl functions.

https://science.sciencemag.org/content/sci/155/3767/1267.full.pdf

Ciguatoxin: Isolation and Chemical Nature

In addition to the previously reported bioactive kahalalide F six new peptides are described. Six of these, including kahalalide F, are cyclic depsipeptides, ranging from a C(31) tripeptide to a C(75) tridecapeptide isolated from a sacoglossan mollusk, Elysiarufescens. The mollusk feeds on a green alga, Bryopsis sp., which has also been shown to elaborate some of these peptides in smaller yields, in addition to an acyclic analog of F, kahalalide G. The bioassay results of antitumor, antiviral, antimalarial, and OI (activity against AIDS opportunistic infections) tests are reported.

Paul J. Scheuer

Papers

Palytoxin: a new marine toxin from a coelenterate.

Ciguatoxin: Isolation and Chemical Nature

Kahalalides: Bioactive Peptides from a Marine Mollusk Elysia rufescens and Its Algal Diet Bryopsis sp.(1).

Kahalalide F: a bioactive depsipeptide from the sacoglossan mollusk Elysia rufescens and the green alga Bryopsis sp

Laulimalides. New potent cytotoxic macrolides from a marine sponge and a nudibranch predator