The Total Syntheses of Phorboxazoles—New Classics in Natural Product Synthesis

Abstract

The marine sponge metabolites phorboxazoles A (see structural formula) and B were the targets of several clever total syntheses, whose special features are described in this Highlight. Now that the synthetic entry to these compounds has been cleared, their cytostatic activity can be studied thoroughly in vitro and in vivo.

Synthetic Efforts toward the Isoindolinone Core of Muironolide A

“…14 Aminal 11 was not detected, but saturated amideester 15 was observed as a result of conjugate addition. 20 Reduction with Li(t-BuO) 3 AlH (entry 4) provided the best, albeit unoptimized, isolated yield of 15 (38%) as a mixture of diastereomers. Treatment of 12 with NaBH 4 and CeCl 3 provided a complex mixture (analyzed by 1 H NMR spectroscopy) in which aminal 11 was not detected.…”

“…3 Only 90 μg of muironolide A was isolated, which meant that total synthesis was the only viable means available to undertake a detailed biological evaluation. 4 Molinski disclosed an intramolecular, organocatalytic approach to an isoindolinone core 5 that utilized imidazolidinone precatalysts.…”

Dependence of the anticancer activity of 1,3‐oxazole derivatives on the donor/acceptor nature of his substitues

“…1,3‐Oxazoles play a vital role in the manufacture of various biologically active drugs as brain‐derived neurotrophic factor inducers, analgesic, trypanocidal activity, antimitotic agents with pro‐apoptotic activity, antibacterial and antituberculosis properties, antifungal activity, anti‐inflammatory, antidepressant, antimicrobial, antidiabetic and antiobesity, antiviral, and analgesic effect . Thus, 1,3‐oxazole could be considered as perspective moiety in the design and further synthesis of novel biologically active agents that exert anticancer activity …”

“…[5,6] Thus, 1,3-oxazole could be considered as perspective moiety in the design and further synthesis of novel biologically active agents that exert anticancer activity. [1][2][3][4][23][24][25][26][27][28][29][30][31][32][33][34] So, the QSAR models were developed for wide site of 1,3-oxazole derivatives showing inhibitory effect on the NCI-60 cancer cell lines, [2,35] and the well correlation was established between many descriptors and biological activity. So, it was investigated the interaction of the azole derivatives with the tubulin inhibitors which significantly improve the clinical effectivity of novel proposed biological active molecules as anticancer agents.…”

A synthetic approach to the phorboxazoles—synthesis of the exocyclic fragment

“…6,7 These efforts have resulted in a number of groups reporting on their total or partial syntheses which were recently reviewed. 8,9 This has prompted us to disclose our own synthetic approach to these natural products.…”