Relative and Absolute Stereochemistry of Diacarperoxides: Antimalarial Norditerpene Endoperoxides from Marine Sponge Diacarnus megaspinorhabdosa

Abstract

Five new norditerpene endoperoxides, named diacarperoxides H–L (1–5), and a new norditerpene diol, called diacardiol B (6), were isolated from the South China Sea sponge, Diacarnus megaspinorhabdosa. Their structures, including conformations and absolute configurations, were determined by using spectroscopic analyses, computational approaches and chemical degradation. Diacarperoxides H–J (1–3) showed some interesting stereochemical issues, as well as antimalarial activity.

Marine Pharmacology in 2014–2015: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, Antiviral, and Anthelmintic Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…As shown in Table 1 and Figure 1, potent (IC 50 < 2 µM) to moderate (IC 50 > 2-10 µM) antimalarial activity was reported for several marine natural products (85)(86)(87)(88)(89)(90)(91)(92)(93)(94), although the mechanism of action for these compounds remained undertermined at the time of publication. Cheng and colleagues reported potent antiplasmodial activity in the peptide actinoramide A (85) isolated from Streptomyces species "in all five (P. falciparum) lines retested" [88].…”

New Metabolites from the South China Sea Sponge <i>Diacarnus megaspinorhabdosa</i>

“…16) As our previous chemical research on the sponge D. megaspinorhabdosa, five norterpene cyclic peroxides diacarperoxides H-L have been isolated. 8) However, to the best of our knowledge, there has been little mention of acyclic terpenes and γ-lactones from the genus of sponge Diacarnus. The interesting metabolites and their bioactive significance of D. megaspinorhabdosa promoted us to study this sponge continuously, which has led to the isolation and identification of two new farnesylacetone derivatives 1-2, a new γ-lactone 3, a known dinorditerpenone 4 and four known norsesterterpene peroxides 5-8 ( Fig.…”

“…1) Sponges of genus Diacarnus are recognized as being prolific sources to produce terpene peroxides and related derivatives, which include norterpene ketones, dienes, diols and other types of compounds. [2][3][4][5][6][7][8] From a biosynthetic perspective, the biosynthetic origin of some or all marine norterpene cyclic peroxides involved a common intermediate C6 hydroperoxide, undergoing a "Michael addition" to an adjacent α,β-unsaturated carboxylic acid or ester moiety. 6) As an offshoot of the biosynthetic pathway, the norterpene ketones can be derived from the hydroperoxide carboxylic aid precursor by oxidative degradation.…”

“…3,9-11) Recently, attention has been drawn on these metabolites because of their pharmaceutical properties, including antimalarial, 8,12) antimicrobial, 12) Trypanosoma brucei inhibitory, 13) sea urchin egg cell-division inhibitory, 14) cytotoxic, 4,7,15) antiulcer and antihypotensive activities.…”

“…6) Such ketones are increasingly being identified as minor co-metabolites with norterpene cyclic peroxides. 3,[9][10][11] Recently, attention has been drawn on these metabolites because of their pharmaceutical properties, including antimalarial, 8,12) antimicrobial, 12) Trypanosoma brucei inhibitory, 13) sea urchin egg cell-division inhibitory, 14) cytotoxic, 4,7,15) antiulcer and antihypotensive activities. 16) As our previous chemical research on the sponge D. megaspinorhabdosa, five norterpene cyclic peroxides diacarperoxides H-L have been isolated.…”