Reaction of Dichloronaphthazarins with Sodium Nitrite as a Route to Natural Pigments Echinamines A and B and Related Aminonaphthazarins

Abstract

A series of 6,7-disubstituted 2-hydroxy-3-nitronaphthazarins were prepared by treatment of 2,3-dichloronaphthazarins with sodium nitrite. Acid-catalyzed hydrolysis of a mixture of two isomeric 6(7)-ethoxy-7(6)-ethyl-substituted 2-hydroxy-3-nitronaph­thazarins followed by chromatographic separation led to the individually precursors of echinamines A and B. Further reduction of nitroquinones using various reducing agents gave echinamines and related 3-amino-2-hydroxynaphthazarins in good yields.

5,8-dihydroxy-1,4-naphthoquinones - nucleophilic aromatic substitution - natural products - echinamine A - echinamine B - sodium nitrite - dichloronaphthazarins

References

<A NAME="RZ63711SS-1A">1a</A> Thomson RH. Naturally Occurring Quinones   3rd ed.:  Chapman & Hall; London: 1987. 

<A NAME="RZ63711SS-1B">1b</A> Thomson RH. Naturally Occurring Quinones   4th ed.:  Blackie Academic & Professional; London: 1997. 

<A NAME="RZ63711SS-2">2</A> Biswas KM. Mallik H. J. Indian Chem. Soc.  1986,  53:  448 

<A NAME="RZ63711SS-3A">3a</A> Kaneko T. Mori H. Iwata M. Meguro S. J. Dairy Sci.  1994,  77:  393 

<A NAME="RZ63711SS-3B">3b</A> Mori H. Sato Y. Taketomo N. Kamiyama T. Yoshiyama Y. Meguro S. Sato H. Kaneko T. J. Dairy Sci.  1997,  80:  1959 

<A NAME="RZ63711SS-4">4</A> Soonthrornchareonnon N. Suwanborirux K. Bavovada R. Patarapanich C. Cassady JM. J. Nat. Prod.  1999,  62:  1390 

<A NAME="RZ63711SS-5">5</A> Eckardt K. Tresselt D. Ihn W. Bradler G. Reinhardt G. J. Antibiot.  1982,  35:  1638 

<A NAME="RZ63711SS-6">6</A> Knöll WMJ. Rinehart KL. Wiley PF. Li LH.
J. Antibiot.  1980,  33:  249 

<A NAME="RZ63711SS-7">7</A> Kulanthaivel P. Perun TJ. Belvo MD. Strobel RJ. Paul DC. Williams DC. J. Antibiot.  1999,  52:  256 

<A NAME="RZ63711SS-8">8</A> Spiteller P. Steglich W. J. Nat. Prod.  2002,  65:  725 

<A NAME="RZ63711SS-9">9</A> Spiteller P. Arnold N. Spiteller M. Steglich W. J. Nat. Prod.  2003,  66:  1402 

<A NAME="RZ63711SS-10A">10a</A> Utkina NK. Denisenko VA. Scholokova OV. Virovaya MV. Prokof’eva NG. Tetrahedron Lett.  2003,  44:  101 

<A NAME="RZ63711SS-10B">10b</A> Kondracki ML. Guyot M. Tetrahedron Lett.  1987,  28:  5815 

<A NAME="RZ63711SS-11">11</A> Cai P. Kong F. Ruppen ME. Glaiser G. Carter GT. J. Nat. Prod.  2005,  68:  1736 

<A NAME="RZ63711SS-12">12</A> Cricchio R. Antonini P. Ferrari P. Ripamonti A. Tuan G. Martinelli E. J. Antibiot.  1981,  34:  1257 

<A NAME="RZ63711SS-13A">13a</A> Lu Ch. Shen Y. J. Antibiot.  2007,  60:  649 

<A NAME="RZ63711SS-13B">13b</A> Balerna M. Keller-Schierlein W. Martius C. Wolf H. Zähner H. Arch. Microbiol.  1969,  65:  303 

<A NAME="RZ63711SS-13C">13c</A> Keller-Schierlein W. Meyer M. Zeeck A. Damberg M. Machinek R. J. Antibiot.  1983,  34:  484 

<A NAME="RZ63711SS-13D">13d</A> Mukhopadhyay T. Franco CMM. Reddy GCS. Gangulia BN. Fehlhaber HW. J. Antibiot.  1985,  38:  948 

<A NAME="RZ63711SS-14">14</A> Tandon VK. Yadav DB. Singh RV. Chaturvedi AK. Shukla PK. Bioorg. Med. Chem. Lett.  2005,  15:  5324 

<A NAME="RZ63711SS-15A">15a</A> Giorgi-Renault S. Renault J. Gebel-Servaltes P. Baron M. Paolett C. Cros S. Bissery MC. Lavelte F. Atassi G. J. Med. Chem.  1991,  34:  38 

<A NAME="RZ63711SS-15B">15b</A> Lin TS. Xu SP. Zhu LY. Cosby LA. Sartorelli AC. J. Med. Chem.  1989,  32:  1467 

<A NAME="RZ63711SS-16">16</A> Pachatouridis Ch. Iakovidou Z. Myoglou E. Mourelatos D. Pantazaki AA. Papageorgiou VP. Kotsis A. Liakopoulou-Kyriakides M. Anti-Cancer Drugs  2002,  13:  367 

<A NAME="RZ63711SS-17">17</A> del Corral JMM. Castro MA. Gordaliza M. Martin ML. Gualberto SA. Gamito AM. Cuevas C. San Feliciano A. Bioorg. Med. Chem.  2005,  13:  631 

<A NAME="RZ63711SS-18">18</A> Medina LFC. Hertz PF. Stefani V. Henriques JAP. Zanotto-Filho A. Brandelli A. Biochem. Cell. Biol.  2006,  84:  720 

<A NAME="RZ63711SS-19A">19a</A> Kapadia GJ. Azuine MA. Balasubramanian V. Sridhar R. Pharmacol. Res.  2001,  43:  363 

<A NAME="RZ63711SS-19B">19b</A> Prescott B. J. Med. Chem.  1969,  12:  181 

<A NAME="RZ63711SS-20">20</A> Silva TM. Camara CA. Barbosa TP. Soares AZ. da Cunha LC. Pinto AC. Vargas MD. Bioorg. Med. Chem.  2005,  13:  193 

<A NAME="RZ63711SS-21">21</A> Mischenko NP. Fedoreyev SA. Pokhilo ND. Anufriev VPh. Denisenko VA. Glazunov VP. J. Nat. Prod.  2005,  68:  1390 

<A NAME="RZ63711SS-22">22</A> MacMunn CA. Q. J. Microsc. Sci.  1885,  25:  469 

<A NAME="RZ63711SS-23">23</A> Elyakov GB, Maxim ov OB, Mishchenko NP, Koltsova EA, Fedoreev SA, Glebko LI, Krasovskaya NP, and Artjukov AA. inventors; US  6,410,601.  ; Chem. Abstr. 2000, 132, 284240

<A NAME="RZ63711SS-24A">24a</A> Mishchenko NP. Fedoreev SA. Bagirova VL. Pharm. Chem. J.  2003,  37:  48 

<A NAME="RZ63711SS-24B">24b</A> Stonik VA. Gusev EI. Martynov MYu. Guseva MR. Shchukin MA. Agafonova IG. Mishchenko NP. Fedoreev SA. Dokl. Biol. Sci.  2005,  405:  696 

<A NAME="RZ63711SS-24C">24c</A> Agafonova IG. Kotel’nikov VN. Mishchenko NP. Kolosova NG. Bull. Exp. Biol. Med.  2011,  150:  739 

<A NAME="RZ63711SS-24D">24d</A> Agafonova IG. Kolosova NG. Mishchenko NP. Chaikina EL. Stonik VA. Bull. Exp. Biol. Med.  2007,  143:  467 

<A NAME="RZ63711SS-24E">24e</A> Afanasév SA. Lasukova TV. Chernayvskii AM. Bull. Exp. Biol. Med.  1997,  124:  1217 

<A NAME="RZ63711SS-24F">24f</A> Gakhramanov FS. Kerimov KT. Dzhafarov AI. Bull. Exp. Biol. Med.  2006,  142:  696 

<A NAME="RZ63711SS-25A">25a</A> Lebedev AV. Ivanova MV. Levitsky DO. Life Sci.  2005,  76:  863 

<A NAME="RZ63711SS-25B">25b</A> Lebedev AV. Ivanova MV. Levitsky DO. Hemoglobin  2008,  32:  165 

<A NAME="RZ63711SS-26A">26a</A> Pokhilo ND. Shuvalova MI. Lebedko MV. Sopelnyak GI. Yakubovskaya AYa. Mischenko NP. Fedoreyev SA. Anufriev VPh. J. Nat. Prod.  2006,  69:  1125 

<A NAME="RZ63711SS-26B">26b</A> Pokhilo ND. Yakubovskaya AYa. Denisenko VA. Anufriev VPh . Tetrahedron Lett.  2006,  47:  1385 

<A NAME="RZ63711SS-27">27</A> Mel’man GI. Mishchenko NP. Denisenko VA. Berdyshev DV. Glazunov VP. Anufriev VF. Russ. J. Org. Chem. (Engl. Transl.)  2009,  45:  37 

<A NAME="RZ63711SS-28A">28a</A> Arnone A. Merlini L. Nasini G. Vajna de Pava O. Synth. Commun.  2007,  37:  2569 

<A NAME="RZ63711SS-28B">28b</A> Matsuoka M. Takei T. Kitao T. Chem. Lett.  1979,  627 

<A NAME="RZ63711SS-28C">28c</A> Matsuoka M. Hamano K. Kitao T. Synthesis  1984,  953 

<A NAME="RZ63711SS-28D">28d</A> Bittner S. Lempert D. Synthesis  1994,  917 

<A NAME="RZ63711SS-29">29</A> Yakubovskaya AYa. Pokhilo ND. Mishchenko NP. Anufriev VP. Russ. Chem. Bull. (Engl. Transl.)  2007,  56:  819 

<A NAME="RZ63711SS-30">30</A> Polonik SG. Polonik NS. Denisenko VA. Moiseenko OP. Anufriev VP. Russ. J. Org. Chem. (Engl. Transl.)  2009,  45:  1410 

<A NAME="RZ63711SS-31">31</A> Polonik NS. Anufriev VPh. Polonik SG. Nat. Prod. Commun.  2011,  6:  217 

<A NAME="RZ63711SS-32">32</A> Ulrich H. Richter R. In Houben-Weyl   Vol. 7/3a:  Grundmann C. Georg Thieme; Stuttgart: 1977.  p.533 

<A NAME="RZ63711SS-33">33</A> Buckle DR. Cantello BCC. Smith H. Smith RJ. Spicer BA. J. Med. Chem.  1977,  20:  1059 

<A NAME="RZ63711SS-34">34</A> Min Yu. Malinakova HC. Stagliano KW. J. Org. Chem.  2006,  71:  6648 

<A NAME="RZ63711SS-35">35</A>

Ratios of both isomeric products were measured directly from the integration of ^¹H NMR absorptions of the α-hydroxy group protons, which are common to both of the regioisomers.

<A NAME="RZ63711SS-36A">36a</A>

A more detailed discussion about mechanism of formation of chlorohydroxyquinones is available in ref. 31.

<A NAME="RZ63711SS-36B">36b</A> For information about the ambident nature of the nitrite ion, see: Ono N. Nitro Group in Organic Synthesis   Wiley-VCH; New York: 2001.  p.17 

<A NAME="RZ63711SS-37">37</A> Polonik SG. Pokhilo ND. Makhan’kov VV. Anufriev VF. Chem. Nat. Compd. (Engl. Transl.)  2008,  44:  93 

<A NAME="RZ63711SS-38">38</A>

The mixture of regioisomeric 7-ethyl-2,5,8-trihydroxy-6-methoxy-3-nitronaphthalene-1,4-dione and 6-ethyl-2,5,8-trihydroxy-7-methoxy-3-nitronaphthalene-1,4-dione, which was early synthesized in 90% yield (ref. 31), is a preferable starting material for the preparation of echinamines.

<A NAME="RZ63711SS-39">39</A> Zahn K. Ochwat P. Justus Liebigs Ann. Chem.  1928,  462:  72 

<A NAME="RZ63711SS-40">40</A> Anufriev VF, Elyakov GB, Polonik SG, Pokhilo ND, Shestak OP, Yakuboskaya AYa, Osadchii SA, Tolstikov GA, and Shul’ts EE. inventors; RU  2277083.  ; Chem. Abstr. 2006, 145, 7881J

<A NAME="RZ63711SS-41">41</A> Anufriev VPh. Novikov VL. Malinovskaya GV. Glazunov VP. Synth. Commun.  1997,  27:  119