Norzoanthamine, an alkaloid isolated from Zoanthus sp., can suppress the loss of bone weight and strength in ovariectomized mice. Norzoanthamine derivatives can also strongly inhibit the growth of P-388 murine leukemia cell lines and human platelet aggregation. However, norzoanthamine's densely functionalized complex stereostructure and scarce availability from natural sources have proved a synthetic challenge. We report the stereoselective total synthesis of norzoanthamine in 41 steps, with an overall yield of 3.5% (an average of 92% yield each step).

https://science.sciencemag.org/content/sci/305/5683/495.full.pdf

Total Synthesis of Norzoanthamine

Total synthesis of (+)-fawcettidine.

The zoanthamine alkaloids, a type of heptacyclic marine alkaloid isolated from colonial zoanthids of the genus Zoanthus sp., have distinctive biological and pharmacological properties in addition to their unique chemical structures with stereochemical complexity. Namely, norzoanthamine (1) can suppress the loss of bone weight and strength in ovariectomized mice and has been expected as a promising candidate for a new type of antiosteoporotic drug, while zoanthamine (2) has exhibited potent inhibitory activity toward phorbol myristate-induced inflammation in addition to powerful analgesic effects. Recently, norzoanthamine derivatives were demonstrated to inhibit strongly the growth of P-388 murine leukemia cell lines, in addition to their potent antiplatelet activities on human platelet aggregation. Their distinctive biological properties, combined with novel chemical structures, make this family of alkaloids extremely attractive targets for chemical synthesis. However, the chemical synthesis of the zoanthamine alkaloids has been impeded owing to their densely functionalized complex stereostructures. In this paper, we report the first and highly efficient total syntheses of norzoanthamine (1) and zoanthamine (2) in full detail, which involve stereoselective synthesis of the requisite triene (18) for an intramolecular Diels-Alder reaction via the sequential three-component coupling reactions, the key intramolecular Diels-Alder reaction, and subsequent crucial bis-aminoacetalization as the key steps. Ultimately, we achieved the total synthesis of norzoanthamine (1) in 41 steps with an overall yield of 3.5 % (an average of 92 % yield each step) and that of zoanthamine (2) in 43 steps with an overall yield of 2.2 % (an average of 91 % yield each step) starting from (R)-5-methylcyclohexenone (3), respectively.

Synthetic studies of the zoanthamine alkaloids: the total syntheses of norzoanthamine and zoanthamine.

Enantiospecific formal total synthesis of (+)-fawcettimine.

Recent progress in the isolation and synthesis of Lycopodium alkaloids is reviewed. A general discussion of the importance of Lycopodium alkaloids and a brief outline of their biosynthesis is followed by a comprehensive tabular overview of all alkaloids isolated since the last major review in this area in 2005. This section is followed by a discussion of highlights and milestone achievements in the synthesis of Lycopodium alkaloids. The main section of the article is devoted to recent syntheses of Lycopodium alkaloids. Previous synthetic contributions are briefly outlined to allow a direct comparison of different strategies for the preparation of these important natural products. The literature is covered between 2005 and early 2012.

Lycopodium alkaloids--synthetic highlights and recent developments.

Enantiospecific synthesis of RPR 107880: A new non peptide substance P antagonist

A Convenient Synthesis of (S)-(+)-2-(2-Methoxyphenyl) Propanoic Acid

Fit-for-Purpose Synthesis of an Aza-Cryptophycin Analogue as the Payload for an Antibody–Drug Conjugate

A Convenient Synthesis of (S)‐(+)‐2‐(2‐Methoxyphenyl) Propanoic Acid.

The synthesis of enantiomerically pure RPR 107880 is described. The synthesis strategy is based on the use of the readily available and inexpensive (R)-(+)-pulegone.

F. Decalogne

Papers

Enantiospecific synthesis of RPR 107880: A new non peptide substance P antagonist

A Convenient Synthesis of (S)-(+)-2-(2-Methoxyphenyl) Propanoic Acid

Fit-for-Purpose Synthesis of an Aza-Cryptophycin Analogue as the Payload for an Antibody–Drug Conjugate

A Convenient Synthesis of (S)‐(+)‐2‐(2‐Methoxyphenyl) Propanoic Acid.

Enantiospecific Synthesis of RPR 107880: A New Non-Peptide Substance P Antagonist.