A concise route to spinochrome E (1) (2,3,5,6,7,8-hexahydroxy-1,4-naphthoquinone), a pigment isolated from sea urchins of different species, has been developed starting from either commercially available 5,8-dihydroxy-1,4-naphthoquinone (11) or 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (12). The protocol involves 3 steps, the chlorination of either 11 or 12 to tetrachloronaphthazarin (13), the total nucleophilic substitution of the chlorine atoms in 13 by methoxy groups, and hydrolysis of tetramethyl ether14; this makes possible the preparation of the target compound in overall yields from 41 to 46%.
ZhouD.Y., QinL., ZhuB.W., WangX.D., TanH., YangJ.F., LiD.M., DongX.P., WuH.T., SunL.M., LiX.L., MurataY. (2011) Extraction and antioxidant property of polyhydroxylated naphthoquinone pigments from spines of purple sea urchin Strongylocentrotus nudus. Food Chemistry, 129, 1591–1597.
3.
Utkina NK, Pokhilo ND. (2012) Free radical scavenging activities of naturally occurring and synthetic analogues of sea urchins naphthazarin pigments. Natural Product Communications, 7, 901–904.
4.
MishchenkoN.P., FedoreyevS.A., PokhiloN.D., AnufrievVPh, DenisenkoV.A., GlazunovV.P. (2005) Echinamines A and B, first aminated hydroxynaphthazarins from the sea urchin Scaphechinus mirabilis. Journal of Natural Products, 68, 1390–1393.
BoguslavskayaL.V., KhrapovaN.G., MaximovO.B. (1985) Polyhydroxynaphthoquinones –a new class of natural antioxidants. Bulletin of the Academy of Sciences of the USSR, Division of Chemical Sciences, 34, 1345–1350 [English translation].
7.
StekhovaS.I., ShentsovaE.B., KoltsovaE.A., KuleshN.I. (1988) Antimicrobial activity of polyhydroxynaphthoquinones from sea urchins. Antibiotics and Chemotherapy, 33, 831–833 [English translation].
8.
NaidenkoT. (1997) Cryopreservation of Crassostrea gigas oocytes, embryos and larvae using antioxidant echinochrome A and antifreeze protein AFP1. Cryoletters, 18, 375–382.
9.
AnufrievVPh, NovikovV.L., MaximovO.B., ElyakovG.B., LevitskyD.O., LebedevA.V., SadretdinovS.M., ShvilkinA.V., AfonskayaN.I., RudaM.Y., CherpachenkoN.M. (1998) Synthesis of some hydroxynaphthazarins and their cardioprotective effects under ischemia-reperfusion in vivo. Bioorganic and Medicinal Chemistry Letters, 8, 587–592.
10.
LebedevA.V., LevitskayaE.L., TikhonovaE.V., IvanovaM.V. (2001) Antioxidant properties, autooxidation and mutagenic activity of echinochrome A compared with its etherified derivative. Biochemistry (Moscow), 66, 885–893.
11.
HatateH., MurataH., HamaY., TanakaR., SuzukiN. (2002) Antioxidative activity of spinochromes extracted from shells of sea urchins. Fisheries Science, 68, 1641–1642.
12.
MishchenkoN.P., FedoreyevS.A., BagirovaV.L. (2003) Histochrome: a new original domestic drug. Pharmaceutical Chemistry Journal, 37, 48–52.
13.
LebedevA.V., IvanovaM.V., LevitskyD.O. (2005) Echinochrome, a naturally occurring iron chelator and free-radical scavenger in artifical and natural membrane systems. Life Sciences, 76, 863–875.
14.
LebedevA.V., IvanovaM.V., LevitskyD.O. (2008) Iron chelators and free-radical scavenger in naturally occurring polyhydroxylated 1,4-naphthoquinones. Hemoglobin, 32, 165–179.
15.
KuwaharaR., HatateH., YukiT., MurataH., TanakaR., HamaY. (2009) Antioxidant property of polyhydroxylated naphthoquinone pigments from shells of purple sea urchins Anthocidaris crassispina. LWT–Food Science and Technology, 42, 1296–1300
16.
PozharitskayaO.N., ShikovA.N., MakarovaM.N., IvanovaS.A., KosmanV.M., MakarovV.G., BazgierV., BerkaK., OtyepkaM., UlrichovaJ. (2013) Antiallergic effects of pigments isolated from green sea urchin (Strongylocentrotus droebachiensis) shells. Planta Medica, 79, 1698–1704.
17.
SinghI., MooreR.E., ChangC.W.J., ScheuerP.J. (1965) The synthesis of spinochromes A, C, D, and E. Journal of the American Chemical Society, 87, 4023–4024.
BorisovaK.L., AnufrievVPh. (2012) Simple preparative synthesis of spinochrome E, a pigment from sea urchins of the genus Echinothrix. Chemistry of Natural Compounds, 48, 202–204.
20.
AnufrievVPh, NovikovV.L., MalinovskayaG.V., GlazunovV.P. (1997) A convenient method for the selective alkylation of β-OH groups of 2(3)-hydroxyjuglones and hydroxynaphthazarins. Synthetic Communications, 27, 119–126.
21.
HuotR., BrassardP. (1974) Friedel-Crafts condensation with maleic anhydrides. III. The synthesis of polyhydroxylated naphthoquinones. Canadian Journal of Chemistry, 52, 838–842.
22.
AttenburrowJ., CameronA.F.B., ChapmanJ.H., EvansR.M., HemsB.A., JansenA.B.A., WalkerT. (1952) A synthesis of vitamin A from cyclohexanone. Journal of the Chemical Society, 1094–1111.
AnufrievVPh, NovikovV.L. (1995) Fluoride salts-alcohols-alumina as reagents for nucleophilic substitution of chlorine atoms for alkoxy groups in 2,3-dichlorosubstituted juglones, naphthazarins, and quinizarins. Tetrahedron Letters, 36, 2515–2518.
25.
MalinovskayaG.V., ChizhovaA.Y., AnufrievVPh. (1999) Chemistry of naphthazarin derivatives. 4. A simple preparative synthesis of mompain. Russian Chemical Bulletin, 48, 1010–1011.