Mycophenolic Acid: Biogenesis, Compound Isolation, Biological Activity, and Historical Advances in Total Synthesis

Abstract

The 6‐alkyl‐2,4‐dihydroxybenzoate moiety known commonly as resorcylate occurs widely as a building block in various fused cyclic systems of bioactive natural products and analogues. Among these many isolated active molecules, mycophenolic acid (MPA) was one of the most studied for its structural features and its potential biological activity. This perspective article portrays the unique biosynthetic interrelationships of polyketide formations in to resorcylates, which are implemented by recent biomimetic/chemical synthetic investigations of the natural product target. The resorcylate, MPA have remained as interesting targets for total synthesis in many laboratories worldwide. There are 13 syntheses reported for MPA to date (Scifinder search). The synthetic strategies for this potential lead compound was an evolution of various methods from generating the highly‐substituted aromatic system via employing simple and commercially available materials to the catalytic methods employed which always involve linear sequences; convergent approaches to the most important protecting group‐free syntheses are also briefly documented in this critical review. This natural product has been the subject of considerable synthetic study. Most reported total syntheses employ 6‐alkyl‐2,4‐hydroxybenzoic acids (lactones) as intermediates and proceed via stepwise derivatization to introduce other functionalities.

“Lighting up” fluoride: cellular imaging and zebrafish model interrogations using a simple ESIPT-based mycophenolic acid precursor-based probe

“…Mycophenolic acid 31 and its derivatives are by now widely studied. Such molecules are applied in different research fields, because of their water solubility and suitability for further research in living cells etc .…”

Unveiling the Microbial Diversity and Associated Secondary Metabolism on Black Apples

“…Outside of the 15 strains selected for OSMAC analysis were other secondary metabolites from other fungal species detected in black apples, namely: mycophenolic acid, a highly biologically-active metabolite found Penicillium brevicompactum and other fungi,(56–58) aurofusarin, from the wheat pathogen Fusarium sp.,(59), enniatins from F. culmorum , the structurally-related xanthoepocin, a common metabolite from the Penicillium genus,(60, 61) asperphenamate, derived from several Aspergillaceae,(62–66) and berkedrimane A originally described from a P. solitum strain. (67) However, we speculate that the latter strain was misidentified, since we have never found berkedrimanes to be produced by any P. solitum strain.…”

Total Synthesis of Geranyl-Resorcinols Isolated from Mushrooms of Genus Hericium

“…A related review on the tetraketide-terpenoid hybrid, mycophenolic acid and its mycophenolate mofetil immunosuppressive prodrug, has been summarized by Churchill and coworkers regarding biogenesis, biological activities, and total syntheses. 51 Some of the synthetic methods described herein are closely related to those for Template for SYNTHESIS Thieme mycophenolic acid, and therefore this review complements the previous review, but chiefly focuses on the geranyl-resorcinols derived from mushrooms of genus Hericium, which do not have a methyl substituent in the aromatic moiety.…”