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China Biotechnology
China Biotechnology  2015, Vol. 35 Issue (10): 115-121    DOI: 10.13523/j.cb.20151017
The Research Progress of Marine Functional Molecules Phloroglucinol
WANG Rong-hua2, SUN Xiu-juan1, LI Qian1, YAN Zhen-xin1, Peter Proksch1
1. Shouguang Fukang Pharmaceutical Co.Ltd.R&D, Shouguang 262700, China;
2. Weihai Municipal Maternal and Child Health Hospita Pharmacy Departmentl, Weihai 264200, China
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The marine pharmacology research is getting stronger and stronger. Recent research has focused on the study of specific activity of marine natural products, and applied to new drugs for human. Phloroglucinol is a kind of important pharmaceutical intermediates. It is widely distributed in marine alga,especially in Phaeophyta. As a non-atropine non-papaverine class smooth muscle spasmolysis medicine,phloroglucinol primarily treat a variety of acute spasmodic pain. It is the first choosed drug in the treatment of gastrointestinal, genitourinary tract spasms and contractions during pregnancy, for its fast-acting, less side effects. Now, phloroglucinol is mainly produced by chemical synthesis. But the chemical method has many disadvantages, so biological synthesis become a potential method and research hot spot to produce phloroglucinol. The mechanisms and the methods of phloroglucinol biosynthesis are reviewed. In addition, it also sums up the main applications of phloroglucinol.

Key wordsPhloroglucinol      Biosynthesis      Chemical synthesis      Application     
Received: 02 April 2015      Published: 25 October 2015
ZTFLH:  Q819  
Cite this article:

WANG Rong-hua, SUN Xiu-juan, LI Qian, YAN Zhen-xin, Peter Proksch. The Research Progress of Marine Functional Molecules Phloroglucinol. China Biotechnology, 2015, 35(10): 115-121.

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[1] Singh I P, Bharate S B. Phloroglucinol compounds of natural origin. Natural Product Reports, 2006, 23(4): 558-591.
[2] Glombitza K W, Keusgen M. Fuhalols and deshydroxyfuhalols from the brown alga Sargassum spinuligerum. Phytochemistry, 1995, 38(4): 987-995.
[3] Keusgen M, Glombitza K W. Phlorethols, fuhalols, and their derivatives from the brown alga Sargassum spinulligerum. Phytochemistry,1995,(04):975-998.
[4] Keusgen M, Glombitza K W. Pseudofuhalols from the brown alga Sargassum spinuligerum. Phytochemistry, 1997, 46(8): 1403-1415.
[5] Glombitza K W, Hauperich S. Phlorotannins from the brown alga Cystophora torulosa. Phytochemistry, 1997, 46(4): 735-740.
[6] Sailler B, Glombitza K W. Phlorethols and fucophlorethols from the brown alga Cystophora retroflexa. Phytochemistry, 1999, 50(5): 869-881.
[7] Glombitza K W, Schmidt A. Trihydroxyphlorethols from the brown alga Carpophyllum angustifolium. Phytochemistry, 1999, 51(8): 1095-1100.
[8] Glombitza K W, Rösener H U, Vilter H, et al. Antibiotics from algae. 8. phloroglucinol from Phaeophyceae. Planta Medica, 1973, 24(4): 301-303.
[9] Belekar V, Shah A, Garg P. High-throughput virtual screening of phloroglucinol derivatives against HIV-reverse transcriptase. Molecular Diversity, 2013, 17(1): 97-110.
[10] Artan M, Li Y, Karadeniz F, et al. Anti-HIV-1 activity of phloroglucinol derivative, 6,6'-bieckol, from Ecklonia cava. Bioorganic & Medicinal Chemistry, 2008, 16(17): 7921-7926.
[11] Jafri W, Yakoob J, Hussain S, et al. Phloroglucinol in irritable bowel syndrome. The Journal of the Pakistan Medical Association, 2006, 56(1): 5-8.
[12] 汪艳红, 韩炜珍. 间苯三酚在产妇自然分娩中的临床应用. 中国医院药学杂志, 2004, 24(2): 96-99. Wang Y H, Han W Z. Clinical application of phloroglucinol in vaginal delivery. Chinese Journal of Hospital Pharmacy, 2004, 24(2): 96-99.
[13] 诸爱士, 徐华新, 郑士辉. 间苯三酚的合成. 中国医药工业杂志, 2000, 31(2): 80-91. Zhu A S, Xu H X, Zheng S H. Synthesis of phloroglucinol. Chinese Journal of Pharmaceuticals, 2000, 31(2): 80-91.
[14] Kastens M L, Kaplan J F. TNT into phloroglucinol. Industrial & Engineering Chemistry, 1950, 42(3): 402-413.
[15] Chiyoda T, Hasegawa S, Nakamura M. Method for producing phloroglucin. U.S. Patent, 4,463,199, 1984-7-31.
[16] Chiyoda T, Hasegawa S, Nakamura M. Process for producing phloroglucin. U.S. Patent, 4,469,899, 1984-9-4.
[17] Chiyoda T, Hasegawa S, Nakamura M. Method for producing 1, 3, 5-triisopropylbenzene trihydroperoxides. U.S. Patent, 4,455,440, 1984-6-19.
[18] 陈杨英, 赵德丰. 间苯三酚的合成研究. 染料工业, 2001, 38(4): 24-25. Chen Y Y, Zhao D F. Research of phloroglucinol synthesis. Dyeindustry, 2001, 38(4): 24-25.
[19] Maegerlein H, Zielke R. Process for the preparation of phloroglucinol. U.S. Patent, 4,296,260, 1981-10-20.
[20] Shanahan P, O'sullivan D J, Simpson P, et al. Isolation of 2,4-diacetylphloroglucinol from a Fluorescent pseudomonad and investigation of physiological parameters influencing its production. Appl Environ Microbiol, 1992, 58(1): 353-358.
[21] Bangera M G, Thomashow L S. Characterization of a genomic locus required for synthesis of the antibiotic 2,4-diacetylphloroglucinol by the biological control agent Pseudomonas fluorescens Q2-87. Molecular Plant-microbe Interactions, 1996, 9(2): 83-90.
[22] Bangera M G, Thomashow L S. Identification and characterization of a gene cluster for synthesis of the polyketide antibiotic 2,4-diacetylphloroglucinol from Pseudomonas fluorescens Q2-87. Journal of Bacteriology, 1999, 181(10): 3155-3163.
[23] Moynihan J A, Morrissey J P, Coppoolse E R, et al. Evolutionary history of the phl gene cluster in the plant-associated bacterium Pseudomonas fluorescens. Appl Environ Microbiol, 2009, 75(7): 2122-2131.
[24] Achkar J, Xian M, Zhao H, et al. Biosynthesis of phloroglucinol. Journal of the American Chemical Society, 2005, 127(15): 5332-5243.
[25] Haas D, Keel C. Regulation of antibiotic production in root-colonizing Peudomonas spp. and relevance for biological control of plant disease. Annual Review of Phytopathology, 2003, 41(1):37-53.
[26] Bender C, Rangaswamy V, Loper J. Polyketide production by plant-associated Pseudomonads. Annual Review of Phytopathology, 1999, 37(1):75-96.
[27] Foo L Y, Lu Y, Howell A B, et al. The structure of cranberry proanthocyanidins which inhibit adherence of uropathogenic P-fimbriated Escherichia coli in vitro. Phytochemistry, 2000, 54(2): 173-181.
[28] 朱峰, 乔建军. 聚酮合成酶底物专一性的研究进展. 中国抗生素杂志, 2006, 31(11): 641-650. Zhu F, Qiao J J. Progress in substrate specificity of polyketide synthase. Chin J Antibiot, 2006,31(11): 641-650.
[29] Cao Y, Jiang X, Zhang R, et al. Improved phloroglucinol production by metabolically engineered Escherichia coli. Applied Microbiology and Biotechnology, 2011, 91(6): 1545-1559.
[30] Randall L P, Woodward M J. The multiple antibiotic resistance (mar) locus and its significance. Research in Veterinary Science, 2002, 72(2): 87-93.
[31] Davis M S, Solbiati J, Cronan J E. Overproduction of acetyl-CoA carboxylase activity increases the rate of fatty acid biosynthesis in Escherichia coli. The Journal of Biological Chemistry, 2000, 275(37): 28593-28604.
[32] Atsumi S, Cann A F, Connor M R, et al. Metabolic engineering of Escherichia coli for 1-butanol production. Metabolic Engineering, 2008, 10(6): 305-311.
[33] 高荣凯, 王芃, 王琰. 采用Red重组系统构建包装菌株DH-gIII. 微生物学杂志, 2008, 4(2): 87-91. Gao R K, Wang F, Wang Y. Adoption of Red recombination system to construct packing strain DH-gIII. Journal of Microbiology, 2008,4(2):87-91.
[34] Gao Hai-Jun, Dan X, Yong-Zheng Y, et al. Cloning,expression and functioning of phlD genes from Pseudomonas fluorescens. Transactions of Beijing Institute of Technology, 2009, 29(5): 465-473.
[35] Zha W, Rubin-Pitel S B, Zhao H. Exploiting genetic diversity by directed evolution: molecular breeding of type III polyketide synthases improves productivity. Molecular bioSystems, 2008, 4(3): 246-258.
[36] Zha W, Rubin-Pitel S B, Shao Z, et al. Improving cellular malonyl-CoA level in Escherichia coli via metabolic engineering. Metabolic Engineering, 2009, 11(3): 192-178.
[37] Cao Y, Xian M. Production of phloroglucinol by Escherichia coli using a stationary-phase promoter. Biotechnology Letters, 2011, 33(9): 1853-1858.
[38] 咸漠, 杨建明, 李强, 等. 微生物催化合成间苯三酚技术. 中国, 2008102254011, 2012-08-15. Xian M, Yang J M, Li Q, et al. Microbial catalytic synthesis technology of phloroglucinol. China, 2008102254011, 2012-08-15.
[39] Rao G, Lee J K, Zhao H. Directed evolution of phloroglucinol synthase PhlD with increased stability for phloroglucinol production. Applied Microbiology and Biotechnology, 2013, 97(13): 5861-5857.
[40] Flavin M T, Rizzo J D, Khilevich A, et al. Synthesis, chromatographic resolution, and anti-human immunodeficiency virus activity of (±)-calanolide A and its enantiomers. Journal of Medicinal Chemistry, 1996, 39(6): 1303-1313.
[41] Dinae F B, Sunzane H. Pharmacoloy and Therapeutics, 2001, 90(2), 157-177.
[42] 高海军, 肖丹, 杨永政, 等. 荧光假单胞菌 phlD 基因的克隆, 表达及功能. 北京理工大学学报, 2009, 29(5): 465-470. Gao H J, Xiao D, Yang Y Z, et al. Cloning, expressing and functioning of phlD gene from Pseudomonads fluorescens. Journal of Beijing Institute of Technology,2009, 29(5): 465-470.
[43] 白雅卉. 间苯三酚用于人工流产的临床观察. 吉林医学, 2010,31(15):2215. Bai Y H. Clinical of observation on abortion with phloroglucinol. Jilin Medical Journal, 2010,31(15):2215.
[44] 刘桃. 斯帕丰(间苯三酚) 在产程中应用的对比观察. 医学理论与实践, 2009, 22(1):18. Liu T. A comparative observation of the effect of spasfon in labour progression. The Journal of Medical Theory and Practice, 2009, 22(1):18.
[45] 吴爱雪,张雷.间苯三酚针治疗妊娠剧吐50例临床观察.现代医药卫生, 2013, 29(3): 424. Wu A X, Zhang L. Clinical observation of 50 cases of phloroglucinol injection in the treatment of hyperemesis gravidarum. Modern Medicine & Health, 2013, 29(3): 424.
[46] 汪宝和, 杨念勇. 间苯三酚合成研究进展. 现代化工, 2003 (z1): 41-43. Wang B H, Yang N Y. Research progress of 1,3,5-Benzenetriol. Modern Chemical Industry, 2003 (z1): 41-43.
[47] Kwon Y H, Jung S Y, Kim J W, et al. Phloroglucinol inhibits the bioactivities of endothelial progenitor cells and suppresses tumor angiogenesis in LLC-tumor-bearing mice. PloS One, 2012, 7(4): e33618.
[48] Liliana M, Mwadham M. Model structures for the study of acylated phloroglucinols and omputational study of the caespitate molecule. Journal of Molecular Structure, 2006, 805: 39-52.
[49] Weller M, Cook J. Suppression of take-all of wheat by seed treatments with Fluorescent pseudomonads. Phytopathology, 1983, 73: 463-469.
[50] 王烨. 产抗生素2,4-diacetyl phloroglucinol(Phl)荧光假单胞菌的分离鉴定及Phl合成基因的克隆. 北京:中国农业大学博士学位论文. Wang Y. Isolation and detection of 2,4-diacelyl phlorogluciniol(Phl)-producing Fluorescent pseudomonads and cloning of phl gene.Beijing:China Agricultural University, 2001.

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