View source for Marinone

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| ImageFile      = Marinone.svg
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| IUPACName      = (4a''R'',5''S'',12b''S'')-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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| PubChem = 10458149
| ChemSpiderID = 8633563
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| ChEBI = 202893
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| StdInChI=1S/C25H27BrO5/c1-12(2)6-5-9-25(4)15-8-7-13(3)10-14(15)18-22(29)20-19(23(30)24(18)31-25)16(27)11-17(28)21(20)26/h6,10-11,14-15,27-28H,5,7-9H2,1-4H3/t14-,15+,25-/m0/s1
| StdInChIKey = DONXAKUQFKTOAJ-AYNSBQOLSA-N
| SMILES = CC1=C[C@H]2[C@@H](CC1)[C@](OC3=C2C(=O)C4=C(C3=O)C(=CC(=C4Br)O)O)(C)CCC=C(C)C
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| Section2       = {{Chembox Properties
| C=25 | H=27 | Br=1 | O=5
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| Section8       = {{Chembox Related
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| OtherCompounds = [[Debromomarinone]]
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'''Marinone''' is an [[antibiotic]] made by marine [[actinomycetes]].<ref>{{Cite journal | vauthors = Pathirana C, Jensen PR, Fenical W |date=December 1992 |title=Marinone and debromomarinone: Antibiotic sesquiterpenoid naphthoquinones of a new structure class from a marine bacterium |journal=Tetrahedron Letters |language=en |volume=33 |issue=50 |pages=7663–7666 |doi=10.1016/0040-4039(93)88010-G}}</ref>
== Biosynthesis ==
The proposed biosynthesis of marinone was first reported by Murray ''et al.'' in 2018.<ref name="auto">{{cite journal | vauthors = Murray LA, McKinnie SM, Pepper HP, Erni R, Miles ZD, Cruickshank MC, López-Pérez B, Moore BS, George JH | display-authors = 6 | title = Total Synthesis Establishes the Biosynthetic Pathway to the Naphterpin and Marinone Natural Products | journal = Angewandte Chemie | volume = 57 | issue = 34 | pages = 11009–11014 | date = August 2018 | pmid = 29935040 | doi = 10.1002/anie.201804351 | pmc = 6248334 }}</ref> 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.<ref>{{cite journal | vauthors = Shen X, Wang X, Huang T, Deng Z, Lin S | title = Naphthoquinone-Based Meroterpenoids from Marine-Derived ''Streptomyces'' sp. B9173 | journal = Biomolecules | volume = 10 | issue = 8 | page = 1187 | date = August 2020 | pmid = 32824158 | pmc = 7463872 | doi = 10.3390/biom10081187 | doi-access = free }}</ref> 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<ref>{{cite journal | vauthors = Kuzuyama T, Noel JP, Richard SB | title = Structural basis for the promiscuous biosynthetic prenylation of aromatic natural products | journal = Nature | volume = 435 | issue = 7044 | pages = 983–987 | date = June 2005 | pmid = 15959519 | pmc = 2874460 | doi = 10.1038/nature03668 | bibcode = 2005Natur.435..983K }}</ref> or by CnqP3 or CnqP4 in marinone biosynthesis.<ref>{{cite journal | vauthors = Motohashi K, Irie K, Toda T, Matsuo Y, Kasai H, Sue M, Furihata K, Seto H | display-authors = 6 | title = Studies on terpenoids produced by actinomycetes. 5-dimethylallylindole-3-carboxylic Acid and A80915G-8"-acid produced by marine-derived Streptomyces sp. MS239 | journal = The Journal of Antibiotics | volume = 61 | issue = 2 | pages = 75–80 | date = February 2008 | pmid = 18408326 | doi = 10.1038/ja.2008.113 | s2cid = 29628302 | doi-access = free }}</ref> 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.
[[File:Biosynthesis Pathway Fig.gif|thumb|700x700px|Proposed biosynthetic pathway of marinone <ref name="auto"/>|center]]
== References ==
{{Reflist}}
== External links ==
* [https://www.ncbi.nlm.nih.gov/pubmed/7710421 Bioactive compounds from marine actinomycetes]
[[Category:Antibiotics]]
[[Category:Angucyclines]]
[[Category:Heterocyclic compounds with 4 rings]]
[[Category:Bromoarenes]]
[[Category:Oxygen heterocycles]]
[[Category:Terpeno-phenolic compounds]]