Marinone
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| IUPAC name
(4aR,5S,12bS)-11-Bromo-8,10-dihydroxy-2,5-dimethyl-5-(4-methylpent-3-enyl)-3,4,4a,12b-tetrahydronaphtho[2,3-c]isochromene-7,12-dione
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3D model (JSmol)
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PubChem CID
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CompTox Dashboard (EPA)
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| Properties | |
| C25H27BrO5 | |
| Molar mass | 487.390 g·mol−1 |
| Related compounds | |
Related compounds
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Debromomarinone |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Marinone is an antibiotic made by marine actinomycetes.[1]
Biosynthesis
[edit]The proposed biosynthesis of marinone was first reported by Murray et al. in 2018.[2] The biosynthesis of marinone begins with 1,3,6,8-tetrahydroxynaphthalene (THN), which is known to be biosynthesized via the condensation of five malonyl-coenzyme A units followed by the aromatization of the resulting pentaketide using a type III polyketide synthase.[3] Next, THN undergoes geranylation or farnesylation at the C-4 position, yielding 1 (Fig. 1). This transformation is catalyzed in vivo by NphB aromatic prenyltransferase in naphterpin biosynthesis[4] or by CnqP3 or CnqP4 in marinone biosynthesis.[5] Then, 1 undergoes oxidative dearomatization which is catalyzed by VCPO, which is a vanadium-dependent chloroperoxidase enzyme. This transformation yields compound 2. Compound 2 then undergoes two consecutive chlorinations at the C2 position, catalyzed by VCPO, to yield 4. Next, a VCPO catalyzed α-hydroxyketone rearrangement shifts the geranyl substituent from C-4 to C-3, yielding 5. Exposure of 5 to mildly basic conditions induces cyclization to yield the α-chloroepoxide, 6. This is followed by the reductive halogenation of the α-chloroepoxide to yield the hydroxynaphthoquinone, 7. Next, oxidation at the C-2 position and facile E/Z isomerization of the double bond affords the enone, 8, which undergoes a intramolecular hetero-Diels-Alder to yield debromomarinone. Lastly, the vanadium-dependent bromoperoxidase catalyzes the bromination of debromomarinone at the C-5 position to result in the formation of marinone.
References
[edit]- ^ Pathirana C, Jensen PR, Fenical W (December 1992). "Marinone and debromomarinone: Antibiotic sesquiterpenoid naphthoquinones of a new structure class from a marine bacterium". Tetrahedron Letters. 33 (50): 7663–7666. doi:10.1016/0040-4039(93)88010-G.
- ^ a b Murray LA, McKinnie SM, Pepper HP, Erni R, Miles ZD, Cruickshank MC, et al. (August 2018). "Total Synthesis Establishes the Biosynthetic Pathway to the Naphterpin and Marinone Natural Products". Angewandte Chemie. 57 (34): 11009–11014. doi:10.1002/anie.201804351. PMC 6248334. PMID 29935040.
- ^ Shen X, Wang X, Huang T, Deng Z, Lin S (August 2020). "Naphthoquinone-Based Meroterpenoids from Marine-Derived Streptomyces sp. B9173". Biomolecules. 10 (8): 1187. doi:10.3390/biom10081187. PMC 7463872. PMID 32824158.
- ^ Kuzuyama T, Noel JP, Richard SB (June 2005). "Structural basis for the promiscuous biosynthetic prenylation of aromatic natural products". Nature. 435 (7044): 983–987. Bibcode:2005Natur.435..983K. doi:10.1038/nature03668. PMC 2874460. PMID 15959519.
- ^ Motohashi K, Irie K, Toda T, Matsuo Y, Kasai H, Sue M, et al. (February 2008). "Studies on terpenoids produced by actinomycetes. 5-dimethylallylindole-3-carboxylic Acid and A80915G-8"-acid produced by marine-derived Streptomyces sp. MS239". The Journal of Antibiotics. 61 (2): 75–80. doi:10.1038/ja.2008.113. PMID 18408326. S2CID 29628302.