A simple and effective synthesis of spinochrome D (1) (2,3,5,6,8-pentahydroxy-1,4-naphthoquinone), a pigment of different sea urchin species, has been developed starting from 2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (13), easily available by cycloacylation of 1,4-dimethoxybenzene (11) with dichloromaleic anhydride (12). Bromination of 13 with either bromine or dioxane dibromide to 6-bromo-2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone (21), followed by nucleophilic substitution of the halogen atoms by methoxy groups in 21 and hydrolysis of trimethyl ether 10 produce the target compound in overall yield from 62 to 65%.
MishchenkoNP, FedoreyevSA, BagirovaVL. (2003) Histochrome: a new original domestic drug. Pharmaceutical Chemistry Journal, 37, 48–52.
5.
HatateH, MurataH, HamaY, TanakaR, SuzukiN. (2002) Antioxidative activity of spinochromes extracted from shells of sea urchins. Fisheries Science, 68, 1641–1642.
6.
LebedevAV, IvanovaMV, LevitskyDO. (2008) Iron chelators and free-radical scavenger in naturally occurring polyhydroxylated 1,4-naphthoquinones. Hemoglobin, 32, 165–179.
7.
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.
8.
ZhouDY, QinL, ZhuBW, WangXD, TanH, YangJF, LiDM, DongXP, WuHT, SunLM, LiXL, MurataY. (2011) Extraction and antioxidant property of polyhydroxylated naphthoquinone pigments from spines of purple sea urchin Strongylocentrotus nudus. Food Chemistry, 129, 1591–1597.
9.
UtkinaNK, PokhiloND. (2012) Free radical scavenging activities of naturally occurring and synthetic analogues of sea urchin naphthazarin pigments. Natural Product Communications, 7, 901–904.
10.
ArtyukovAA, PopovAM, TsybulskyAV, KrivoshapkoON, PolyakovaNV. (2013) Pharmacological activity of echinochrome A alone and in the biologically active additive Timarin. Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry, 7, 237–242.
11.
PozharitskayaON, ShikovAN, MakarovaMN, IvanovaSA, KosmanVM, MakarovVG, BazgierV, BerkaK, OtyepkaM, UlrichovaJ. (2013) Antiallergic effects of pigments isolated from green sea urchin (Strongylocentrotus droebachiensis) shells. Planta Medica, 79, 1698–1704.
12.
PelageevDN, PanchenkoMN, PokhiloND, AnufrievVPh. (2010) Synthesis of 2,2′-(ethane-1,1-diyl)bis(3,5,6,7,8-pentahydroxy-1,4-naphthoquinone), a metabolite of the sea urchins Spatangus purpureus, Strongylocentrotus intermedius, and S. droebachiensis. Russian Chemical Bulletin, International Edition, 59, 1472–1476.
13.
AndersonHA, SmithJ, ThomsonRH. (1965) Naturally occurring quinones. Part VI. Spinochrome D. Journal of the Chemical Society, 2141–2144.
14.
SinghI, MooreREChangCWJ, ScheuerPJ. (1965) The synthesis of spinochromes A, C, D, and E. Journal of the American Chemical Society, 87, 4023–4024.
BalanevaNN, ShestakOPAnufrievVPh, NovikovVL. (2016) Synthesis of spinochrome D, a metabolite of various sea-urchin species. Chemistry of Natural Compounds, 52, 213–217.
17.
AnufrievVPh, NovikovVL., (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.
18.
MasudaK. (1987) Naphthazarin derivatives as antitumor agents. Japan Patent: JP 62289543 A. Chemical Abstracts, (1990), 112, 42566.
19.
MasudaK. (1995) Preparation of 2,3,6-trichloronaphthazarin and preparation of antitumor agents. Japan Patent: JP 07215906 A. Chemical Abstracts, (1995) 124, 86608.
20.
MasudaK. (1995) Preparation of antitumor 6-chloro-2,3-dimethoxynaphthazarin. Japan Patent: JP 07215907 A. Chemical Abstracts, (1995) 124, 86609.
21.
MasudaK. (1995) Preparation of antitumor 2,3,6-trimethoxynaphthazarin. Japan Patent: JP 07215908 A. Chemical Abstracts, (1995) 124, 86610.
22.
NovikovVL, BalanevaNN, ShestakOPAnufrievVPh, GlazunovVP. (2016) Cycloacylation of dimethyl ethers of chloro substituted hydroquinones with dichloromaleic anhydride. Russian Chemical Bulletin, International Edition, 65, 993–1003.
23.
HuotR, BrassardP. (1974) Friedel-Crafts condensations with maleic anhydrides. III. The synthesis of polyhydroxylated naphthoquinones. Canadian Journal of Chemistry, 52, 838–842.
24.
MasudaK, FunayamaS, KomiyamaK, UmezawaI. (1987) Constituents of Tritonia crocosmaeflora L. Tricrozarin B, an antitumor naphthazarin derivative. Journal of Natural Products, 50, 958–960.
