DOCSLIB.ORG

A Genomics‑Guided Study of the Biosynthesis of Microbial Secondary Metabolites

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Genomics‑Guided Study of the Biosynthesis of Microbial Secondary Metabolites This document is downloaded from DR‑NTU (https://dr.ntu.edu.sg) Nanyang Technological University, Singapore. A genomics‑guided study of the biosynthesis of microbial secondary metabolites Chakrabortti, Alolika 2016 Chakrabortti, A. (2016). A genomics‑guided study of the biosynthesis of microbial secondary metabolites. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/68357 https://doi.org/10.32657/10356/68357 Downloaded on 09 Oct 2021 19:21:04 SGT GENOMICS STUDY OF BIOSYNTHESIS OF MICROBIAL SECONDARY METABOLITES 2016 A GENOMICS-GUIDED STUDY OF THE BIOSYNTHESIS OF MICROBIAL SECONDARY METABOLITES A CHAKRABORTTI ALOLIKA CHAKRABORTTI SCHOOL OF BIOLOGICAL SCIENCES 2016 2016 A GENOMICS-GUIDED STUDY OF THE BIOSYNTHESIS OF MICROBIAL SECONDARY METABOLITES A CHAKRABORTTI ALOLIKA CHAKRABORTTI School of Biological Sciences A thesis submitted to the Nanyang Technological University in partial fulfillment of the requirement for the degree of Doctor of Philosophy 2016 Acknowledgement While submitting this doctoral thesis, I would like to take the opportunity of thanking a few people who stood by me and extended their support and assistance to me at all times during the last few years. First and foremost, I would like to thank my Ph.D-Supervisor Assoc. Prof. Liang Zhao- Xun for being such a source of motivation and encouragement. I am immensely thankful to him for giving me the opportunity and freedom to grow as an independent researcher and take up new challenges. At the same time, I am indebted to him for his invaluable insights and inputs on my research. It has been a complete privilege for me to work under his tutelage. I am deeply thankful to my ex-colleagues – Dr. Ho Chun Loong and Dr. Yang Lifeng for their constant guidance and most importantly for standing by me through thick and thin in the last four years. I would also like to extend my gratitude to my ex-labmate and mentor Dr. Mary Chuah for her guidance. I would like to thank and acknowledge the support of Yeo Qin Yi, Denise Seow, Leow Min Li, Ding Yichen, Huang Peng and Cheang Qing Wei for working with me on this project at various stages. I want to express my gratitude towards all my other former and present lab-mates - Prabhadevi Venkataramani, Amanda Tan, Dr. Sun Hui Hua, Ishin Soehano, Swathi Pasunooti, Koh Siew Lee, Dr. Xu Ling Hui, Jamila Oppong, Yong Grace, Xin Lingyi, Pang Li Mei and Low Zhen Zie for their continuous and unfailing camaraderie. I would also like to thank Dr. Nishanth V. Menon, Dr. Manisha Mukherjee, Areetha D’Souza and Dr. Tan Jiazi for their help and support. I am thankful to all my collaborators; Dr. Yoganathan Kanagasundaram (Bioinformatic Institute, A*STAR, Singapore), A/P Liu Xuewei (School of Physical and Mathematical Sciences, Nanyang Technological University), Asst/P Yang Liang (Singapore Centre on Environmental Life Science Engineering, Singapore), Jinming Li (Southern Medical University, China) and A/P Mark Turner (School of Agriculture and Food Sciences, University of Queensland). I would like to express my sincere gratitude to Dr. Yit Heng Chooi, Research fellow, (College of Medicine, Biology and Environment, Autralian National University) for his advice on the bioinformatic analysis during the early days of the project. Page | i I am extremely thankful to my Thesis Advisory Committee (TAC) members Prof. James Tam, A/P Liu Chuan Fa, Dr. Tang Kai and Dr. Peter Cheung from the School of Biological Sciences, NTU for their valuable inputs and guidance. I am indebted to Nanyang Technological University and Ministry of Education, Singapore for providing me with the NTU research scholarship and grants necessary for my research. Last but not the least a special thanks to my family and friends. I am eternally thankful to my parents for being my biggest source of strength and inspiration at all times. Words are enough to express how grateful I am to all my friends for their being a part of my support- system in such a huge way. This acknowledgement would be incomplete without the mention of Dr. Arnab Kapat, my mentor at Reliance Life Sciences, India, for I would have probably not been here without his constant encouragement and nudging. I am thankful to him for always having some kind words to inspire and motivate me. Page | ii Table of contents Acknowledgement .............................................................................................................. i Table of contents .............................................................................................................. iii List of figures .................................................................................................................... vi List of Tables .................................................................................................................... ix Abbreviations .....................................................................................................................x Abstract .................................................................................................................... xiii Chapter 1 Introduction ..................................................................................................1 1.1 Microbial secondary metabolites .........................................................................1 1.2 Key concepts .......................................................................................................4 Classes of secondary metabolites .........................................................................................5 Biosynthetic mechanisms and enzymes ...............................................................................6 Regulation of secondary metabolism .................................................................................10 1.3 Genomics guided approach to study secondary metabolism .............................12 1.4 Which microbes to choose for genome-mining? ...............................................17 1.5 Leveraging genomics with other techniques .....................................................18 1.6 Genomics and combinatorial biosynthesis of novel compounds ......................22 1.7 Synthetic biology, metabolomics and secondary metabolism ...........................24 1.8 Genomics and future of secondary metabolism research ..................................26 1.9 Naturally occurring dihydroisocoumarins and their biosynthetic mechanism ..27 1.10 Objectives ..........................................................................................................28 Chapter 2 The complete genome of Aspergillus westerdijkiae and secondary metabolism ......................................................................................................................31 2.1 Introduction .......................................................................................................31 2.2 Materials and methods .......................................................................................35 2.3 Results ...............................................................................................................38 2.4 Discussion .........................................................................................................47 Page | iii Chapter 3 Biosynthesis of ochratoxin A in A. westerdijkiae ....................................49 3.1 Introduction .......................................................................................................49 3.2 Materials and methods .......................................................................................54 3.3 Results ...............................................................................................................59 3.4 Discussion .........................................................................................................64 Chapter 4 Biosynthesis of circumdatins and other peptidyl alkaloids in A. westerdijkiae .................................................................................................................69 4.1 Introduction .......................................................................................................69 4.2 Materials and method ........................................................................................72 4.3 Results ...............................................................................................................72 4.4 Discussion .........................................................................................................80 Chapter 5 Genome sequence and biosynthetic potential of Nocardia jinanensis ...83 5.1 Introduction .......................................................................................................83 5.2 Materials and method ........................................................................................87 5.3 Results ...............................................................................................................89 5.4 Discussion .........................................................................................................98 Reference ....................................................................................................................101 Appendix ....................................................................................................................129 Appendix I: Summary of antiSMASH predictions for A. westerdijkiae genome. ...........129 Appendix II: Summary of NRPS and PKS genes in A. westerdijkiae genome………..132
Load more

Recommended publications
  • Ep 1384475 A1
    Europäisches Patentamt *EP001384475A1* (19) European Patent Office Office européen des brevets (11) EP 1 384 475 A1 (12) EUROPEAN PATENT APPLICATION published in accordance with Art. 158(3) EPC (43) Date of publication: (51) Int Cl.7: A61K 31/352, C07D 311/76, 28.01.2004 Bulletin 2004/05 A61P 1/16, A23L 1/30, A23K 1/16 (21) Application number: 02713236.4 (86) International application number: (22) Date of filing: 28.03.2002 PCT/JP2002/003098 (87) International publication number: WO 2002/080904 (17.10.2002 Gazette 2002/42) (84) Designated Contracting States: • KAYAHASHI, Shun, AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU Tsukuba Research Laboratories MC NL PT SE TR Tsukuba-shi, Ibaraki 305-0841 (JP) Designated Extension States: • HASHIZUME, Erika, AL LT LV MK RO SI Tsukuba Research Laboratories Tsukuba-shi, Ibaraki 305-0841 (JP) (30) Priority: 05.04.2001 JP 2001106600 • NAKAGIRI, Ryusuke, Tsukuba Research Laboratories (71) Applicant: KYOWA HAKKO KOGYO CO., LTD. Tsukuba-shi, Ibaraki 305-0841 (JP) Chiyoda-ku, Tokyo 100-8185 (JP) (74) Representative: Casalonga, Axel et al (72) Inventors: BUREAU D.A. CASALONGA - JOSSE • SAKAI, Yasushi, Paul-Heyse-Strasse 33 Foods & Liquors Research Laborat. 80336 München (DE) Inashiki-gun, Ibaraki 300-0398 (JP) (54) LIVER FUNCION PROTECTING OR AMELIORATING AGENT (57) A liver function protecting or improving agent which comprises a compound represented by the formula (I) {in the formula (I), R1,R2,R3,R4,R5,R6,R7,R8and R9 may be the same or different, and represent hydrogen, halogen, hydroxy, alkoxy or alkyl; and RA represents the formula (II) EP 1 384 475 A1 Printed by Jouve, 75001 PARIS (FR) (Cont.
    [Show full text]
  • The Biosynthesis of Ochratoxin a and Other Structurally Related Polyketides by Aspergillus Ochraceus
    The biosynthesis of ochratoxin A and other structurally related polyketides by Aspergillus ochraceus. A thesis submitted in fulfilment of the requirements for the degree of Ph.D. of the University of London. by Jonathan Peter Harris 1996 Department of Biochemistry Imperial College of Science, Technology and Medicine London, SW7 2AY Abstract. This study has revealed new information on the pathway and the dynamics of the biosynthesis of the important mycotoxin ochratoxin A by a particular isolate of Aspergillus ochraceus in the context of the production of other structurally related polyketides including ochratoxins B, a, and 13, mellein, diaporthin and orthosporin. Orthosporin and diaporthin had never been previously found as A. ochraceus metabolites and the metabolic oiigin of diaporthin was found to be from both acetate and methionine. New physico-chemical data were obtained for diaporthin, ochratoxins a and 13, 0-methyl, methylochratoxins A and a, 0-methylochratoxin A and mellein. [ 14C] Labelled primary metabolite precursors and the methylation inhibitor ethionine were used in feeding studies to shaken liquid cultures of A. ochraceus to reveal a distinct early phase of ochratoxin A biosynthesis principally involving acetate. Further isotopic labelling experiments using [ 14C] mellein, [1O- 14C] ochratoxins a and 13 and [1O-14C, phenylalanyl-3H] ochratoxins A and B, all prepared biosynthetically, showed that i) ochratoxin 13 was incorporated into both ochratoxins A and B, ii) ochratoxin a was incorporated only into ochratoxin A, iii) mellein may not be an advanced intermediate in either ochratoxins A or B biosynthesis (which questions the accuracy of proposed biosynthetic schemes) and iv) there was detectable inter-conversion between ochratoxins A and B, albeit non-specifically and at a low rate.
    [Show full text]
  • Vasorelaxant Effects of Methanolic Extract and Principal Constituents of Sweet Hydrangea Leaf on Isolated Rat Aorta
    Journal of the Academic Society for Quality of Life (JAS4QoL) 2018 Vol. 4(1) 2:1-6 Vasorelaxant Effects of Methanolic Extract and Principal Constituents of Sweet Hydrangea Leaf on Isolated Rat Aorta Souichi NAKASHIMA, Seikou NAKAMURA, Takuya IWAMOTO, Yui MASUKAWA, Yuika EMI, Ayako OHTA, Nami NOMURA, Hisashi MATSUDA* Kyoto Pharmaceutical University; Misasagi, Yamashina-ku, Kyoto 607–8 !", #apan. &itation: NAKASHIMA, S.; NAKAMURA, S.; IWAMOTO, T.; MASUKAWA, Y.; EMI, Y.; OHTA, A.; NOMURA, N.; MATSUDA, H. (asorelaxant Effects o, Methanolic *)tract an- Princi$al &onstituents o, ./eet Hy-rangea Leaf on Isolate- Rat Aorta JAS4QoL 2018, 4(1) 2'!-6% 5nline' h6$'77as48ol.org/9$:"08 ;art! 3eceive- Date' "0!870=7"> Acce$te- Date' "0!870=7"6 Pu?lishe-' "0!870 70! 2018 International Conference and Cruise • @e "0!8 2nternational &onference on Aality o, 1i,e /ill ?e a 5-night Genting Dream Cruise leaving Sunday, Sept. 2nd, 2018 ,rom .ingapore, visiting Malaysia, &am?o-ia, 1aem &habang in @ailand, and returning to Singapore on !riday, Sept. 6th, 2018% • Be are no/ calling ,or $apers% Procee-ings as /ell as $hotos and other information ,rom $ast con- ,erences can be found at h6$'77as48ol.org/ic8ol/"0!87 By special arrangement with the cruise operators, Conference attendees will receive a one-time special discount. Full details to be as4qol.org icqol !"#$ accomodations . % 4uthor for correspon-ence (matsu-aDmb%kyoto-$hu%ac%E$F #asorelaxant %ffects of Methanolic %xtract and (rincipal Constituents of S)eet Hydrangea Leaf on Isolated Rat Aorta Souichi NAKASHIMA, Seikou NAKAMURA, Takuya IWAMOTO, Yui MA- SUKAWA, Yuika EMI, Ayako OHTA, Nami NOMURA, and Hisashi MATSUDA* Kyoto Pharmaceutical University; Misasagi, Yamashina-ku, Kyoto 607–8 !", #apan.
    [Show full text]
  • Differentiation Inducing Activities of Isocoumarins from Hydrangea Dulcis Folium
    566 Notes Chem. Pharm. Bull. 48(4) 566—567 (2000) Vol. 48, No. 4 Differentiation Inducing Activities of Isocoumarins from Hydrangea Dulcis Folium Kaoru UMEHARA,* Misae MATSUMOTO, Mitsuhiro NAKAMURA, Toshio MIYASE, Masanori KUROYANAGI, and Hiroshi NOGUCHI School of Pharmaceutical Sciences, University of Shizuoka, 52–1 Yada, Shizuoka 422–8526, Japan. Received September 13, 1999; accepted December 20, 1999 In the course of searching for differentiation inducers against leukemic cells from plants, we have recognized the differentiation inducing activities of the methanolic extract of Hydrangea Dulcis Folium. Activity guided sep- aration of the extract was carried out using M1 cells, and seven isocoumarins were isolated as active substances. These isocoumarins showed the activities at the concentration of 100 mM and non-cytotoxic effects even at 300 mM. Key words differentiation; Hydrangea Dulcis Folium; M1 cell; phagocytosis Differentiation inducers are of potential interest for the shown). They showed hardly any antiproliferative activities, treatment of human cancers promoting the terminal differen- and a more than 70% of growth ratio was found in 300 m M of tiation of certain human tumor cells. We have reported the these compound treated groups. Glucosides were good pro- differentiation inducing activities of triterpenes, flavones, lig- inducers. nans, and steroids.1) These compounds differentiated mouse Isocoumarins (6—8) were recongnized to have higher ac- myeloid leukemia (M1) cells into phagocytic cells, and some tivities than dihydroisocoumarins (1—5). Phagocytic activi- of them also induced the differentiation of human acute ties were observed when M1 cells were treated with 100 m M promyelocytic leukemia (HL-60) cells. In the course of of isocoumarins (6—8) and the activities were nearly equal searching for differentiation inducers against leukemic cells, to 300 m M treated groups of dihydroisocoumarins (1—5).
    [Show full text]
  • Isocoumarins and 3,4-Dihydroisocoumarins, Amazing Natural Products: a Review
    Turkish Journal of Chemistry Turk J Chem (2017) 41: 153 { 178 http://journals.tubitak.gov.tr/chem/ ⃝c TUB¨ ITAK_ Review Article doi:10.3906/kim-1604-66 Isocoumarins and 3,4-dihydroisocoumarins, amazing natural products: a review Aisha SADDIQA1;∗, Muhammad USMAN2, Osman C¸AKMAK3 1Department of Chemistry, Faculty of Natural Sciences, Government College Women University, Sialkot, Pakistan 2Department of Chemistry, Government College of Science, Lahore, Pakistan 3Department of Nutrition and Dietetics, School of Health Sciences, Istanbul_ Geli¸simUniversity, Avcılar, Istanbul,_ Turkey Received: 23.04.2016 • Accepted/Published Online: 10.09.2016 • Final Version: 19.04.2017 Abstract: The isocoumarins are naturally occurring lactones that constitute an important class of natural products exhibiting an array of biological activities. A wide variety of these lactones have been isolated from natural sources and, due to their remarkable bioactivities and structural diversity, great attention has been focused on their synthesis. This review article focuses on their structural diversity, biological applications, and commonly used synthetic modes. Key words: Isocoumarin, synthesis, natural product, biological importance 1. Introduction The coumarins 1 are naturally occurring compounds having a fused phenolactone skeleton. Coumarin 1 was first extracted from Coumarouna odorata (tonka tree). 1 The isocoumarins 2 and 3,4-dihydroisocoumarins 3 are the isomers of coumarin 1. A number of substituted isocoumarins have been found to occur in nature; however, the unsubstituted isocoumarins have not been observed to occur naturally. Furthermore, sulfur, selenium, and tellurium analogues 4a{4c have also been known since early times (Figure 1). Figure 1. Some naturally occurring isocoumarins. The isocoumarins and their analogues occur in nature as secondary metabolites (i.e.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2008/0161324 A1 Johansen Et Al
    US 2008O161324A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0161324 A1 Johansen et al. (43) Pub. Date: Jul. 3, 2008 (54) COMPOSITIONS AND METHODS FOR Publication Classification TREATMENT OF VRAL DISEASES (51) Int. Cl. (76) Inventors: Lisa M. Johansen, Belmont, MA A63/495 (2006.01) (US); Christopher M. Owens, A63L/35 (2006.01) Cambridge, MA (US); Christina CI2O I/68 (2006.01) Mawhinney, Jamaica Plain, MA A63L/404 (2006.01) (US); Todd W. Chappell, Boston, A63L/35 (2006.01) MA (US); Alexander T. Brown, A63/4965 (2006.01) Watertown, MA (US); Michael G. A6II 3L/21 (2006.01) Frank, Boston, MA (US); Ralf A6IP3L/20 (2006.01) Altmeyer, Singapore (SG) (52) U.S. Cl. ........ 514/255.03: 514/647; 435/6: 514/415; Correspondence Address: 514/460, 514/275: 514/529 CLARK & ELBNG LLP 101 FEDERAL STREET BOSTON, MA 02110 (57) ABSTRACT (21) Appl. No.: 11/900,893 The present invention features compositions, methods, and kits useful in the treatment of viral diseases. In certain (22) Filed: Sep. 13, 2007 embodiments, the viral disease is caused by a single stranded RNA virus, a flaviviridae virus, or a hepatic virus. In particu Related U.S. Application Data lar embodiments, the viral disease is viral hepatitis (e.g., (60) Provisional application No. 60/844,463, filed on Sep. hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E). 14, 2006, provisional application No. 60/874.061, Also featured are screening methods for identification of filed on Dec. 11, 2006. novel compounds that may be used to treat a viral disease.
    [Show full text]
  • Teb Dergi Temmuz 2009 SON.FH10
    Turk J. Pharm. Sci. 7 (3), 205-212, 2010 Original article DIHYDROISOCOUMARIN DERIVATIVES ISOLATED FROM THE ROOTS OF SCORZONERA LATIFOLIA Gülçin SALTAN ÇİTOĞLU1, Özlem BAHADIR1, Stefano DALL’ACQUA2 1 Ankara University, Faculty of Pharmacy, Department of Pharmacognosy, 06100, Ankara, TURKEY 2Università degli Studi di Padova, Dipartimento di Scienze Farmaceutiche, Natural Product Lab (NPL),Via Marzolo, 5 - 35100 Padova, ITALY Abstract Scorzonera latifolia (Fisch. & Mey.) DC. is a perennial herb that grows in central and eastern region of Anatolia, Turkey. A traditional mastic named yah sakızı has been prepared from the roots of this plant and used as an analgesic in Turkish folk medicine. In this study, the methanolic extract obtained from the roots of S. latifolia were investigated for the chemical composition. Two dihydroisocoumarin derivatives were isolated from the roots. The compounds were identified as (±) hydrangenol and (-)-scorzotomentosin 4'-0-P-glucopyranoside. The structures were determined using spectroscopic methods ('H-NMR, 13C-NMR, HMBC, HSQQ COSY, TOCSY, NOESY, DEPT) and chemical correlations with known compounds that have been described in the literature. Key words: Scorzonera latifolia, Compositae, (±) Hydrangenol, (-)-Scorzotomentosin 4'-0-/3- glucopyranoside Scorzonera latifolia Köklerinden izole Edilen Dihidroizokumarin Türevi Bileşikler Scorzonera latifolia (Fisch. & Mey.) DC. orta ve doğu Anadolu ’da yetişen gok yilhk bir bitkidir.Bu bitkinin köklerinden Türk halk tıbbında analjezik olarak kullamlan, yah sakızi olarak isimlendirilen geleneksel bir sahz elde edilmektedir. Bu gahsmada, S latifolia köklerinden elde edilen metanollü ekstre kimyasal bileşimi agisından araştinlmistır. İzole edilen bileşikler (±) hidrangenol ve (-)-skorzotomentozin 4'-0-P-glukopiranozit olarak tammlanmistır. Bileşiklerin yapılan spektroskopik metotlar ('H-NMR, 13C- NMR, HMBC, HSQQ COSY, TOCSY, NOESY, DEPT) kullamlarak aydınlatılmis ve literatiir bilgileriyle doğrulanmistır.
    [Show full text]
  • Paper Teplate
    Volume-1 ISSN: 2455-3085 (Online) Issue-4 RESEARCH REVIEW International Journal of Multidisciplinary April-2016 www.rrjournals.com Nomenclature and Structural types Isocoumarins Dr. Rajesh P. Sathwara Associate. Prof., Dept of Chemistry, R.G. Shah Science College, Vasana, Ahmedabad () ___________________________________________________________________________________________________ 1. INTRODUCTION Isocoumarins and 3,4-dihydroisocoumarins are the secondary metabolites1. These are found in wide varieties of fungi, lichens, molds, bacteria, higher plants and insects. Majority of isocoumarins have been isolated from various species of fungal genera Artemisia, Aspergillus, Ceratocystis, Fusarium, Penicillum, and Streptomyces etc. 2. NOMENCLATURE AND STRUCTURAL TYPES The name isocoumarin (1) is derived from the fact that these compounds are isomeric to coumarins(2). Coumarin2 was isolated (1820) from tonka tree formerly known as Coumarounaodorata. In an isocoumarin, a lactonicpyran ring is fused to a benzene ring. The IUPAC and Chemical Abstract name for isocoumarin is 1H-2-benzopyran-1-one, numbered as shown and its 3,4- dihydroanalogue (3) is named as 3,4-dihydroisocoumarin rather than isochroman-1-one. R3 R2 5 4 R4 6 4a R1 3 O 7 R5 8a 8 O R6 1 (1) Isocoumarin O O (2) Coumarin R3 R2 5 4 R4 6 4a R1 3 O 7 R5 8a 8 O R6 1 (3) 3,4-dihydro- analogue As in case of other classes of the natural products (alkaloids, flavonoids etc.) no systematic nomenclature exists for isocoumarins. Majority of naturally occurring isocoumarins and 3,4-dihydroisocoumarins have been assigned trivial names3, which are derived from generic or specific names of source plant and fungi. Examples of the names derived from those of parent genera are agrimonolide (Agrimoniapilosa), fusamarin (Fusarium spp.), alternariol (Alternaria spp.), artemidin (Artemisia glauca), peniolactol (Peniophorasanguinea), cladosporin (Cladosporium spp.), homalicine (Homaliumzeylancum), oosponol (Oospora astringes) etc.
    [Show full text]
  • A New Total Synthesis of Natural Isocoumarin, Thunberginol B
    General Papers ARKIVOC 2007 (xiv) 12-19 A new total synthesis of natural isocoumarin, thunberginol B Ghulam Qadeera, Nasim Hasan Ramaa, * and Syed Jabbar Hussain Shahb a Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan bInstitute of Organic Chemistry, Humbolt University, Brooke-taylor-strasse 2, 12489 Berlin, Germany E-mail: [email protected] Abstract 3,5-Dimethoxyhomophthalic acid is a key intermediate for the synthesis of highly biological active naturally and non-naturally occurring isocoumarins and 3,4-dihydroisocoumarins. It was synthesized efficiently in five steps from 3,5-dimethoxybenzaldehyde (1) via a series of reactions including synthesis of 3,5-dimethoxycinnamic acid (2) and 3-(3′,5′-dimethoxyphenyl)propionic acid (3), cyclization of 3-(3′,5′-dimethoxyphenyl)propionic acid (3) to 5,7-dimethoxy-1- indanone (4) and oxidative decomposition of methyl 2-hydroxy-2-(5,7-dimethyoxy-1-oxo-1H- inden-2(3H)-ylidene)acetate (5) to 3,5-dimethoxyhomophthalic acid (6). Natural isocoumarin, thunberginol B [3-(3′,4′-dihydroxyphenyl)-6,8-dihydroxyisocoumarin] (10) was synthesized by the condensation of 3,5-dimethoxyhomophthalic acid (6) with 3,4-dimethoxybenzoic acid (7) followed by demethylation of intermediate [3-(3′,4′-dimethoxyphenyl)-6,8- dimethoxyisocoumarin] (9). The synthesized compounds were purified by HPLC and characterized by elemental analysis, IR, 1H NMR and mass spectrometry. Keywords: 3,5-Dimethoxyhomophthalic acid, thunberginol B, synthesis, demethylation Introduction Isocoumarin structures are
    [Show full text]
  • Biol. Pharm. Bull. 42(3): 424-431 (2019)
    424 Biol. Pharm. Bull. 42, 424–431 (2019) Vol. 42, No. 3 Regular Article Chemical Constituents from Leaves of Hydrangea serrata and Their Anti-photoaging Effects on UVB-Irradiated Human Fibroblasts Ji-Sun Shin,a Hee-Soo Han,a,b Seung-Bin Lee,a,b Da-bin Myung,a,b Keunsuk Lee,c Sun Hee Lee,c Hyoung Ja Kim,*,d and Kyung-Tae Lee*,a,b a Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University; Seoul 02447, Republic of Korea: b Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University; Seoul 02447, Republic of Korea: c Department of New Material Development, COSMAXBIO; Gyeonggi 13486, Republic of Korea: and d Molecular Recognition Research Center, Materials and Life Science Research Division, Korea Institute of Science and Technology; Seoul 02792, Republic of Korea. Received September 25, 2018; accepted November 28, 2018 Hydrangea serrata (THUNB.) SER. (Hydrangeaceae) leaves have been used as herbal teas in Korea and Japan. The objective of this study was to identify anti-photoaging compounds in aqueous EtOH extract pre- pared from leaves of H. serrata and their effects on UVB-irradiated Hs68 human foreskin fibroblasts. Phyto- chemical study on H. serrata leaves led to the isolation and characterization of ten compounds: hydrangenol, thunberginol A, thunberginol C, hydrangenoside A, hydrangenoside C, cudrabibenzyl A, 2,3,4-trihydroxys- tilbene, thunberginol F, quercetin 3-O-β-D-xylopyranosyl (1-2)-β-D-galactopyranoside, quercetin 3-O-β-D- xylopyranosyl (1-2)-β-D-glucopyranoside. Cudrabibenzyl A, 2,3,4-trihydroxystilbene, quercetin 3-O-β-D- xylopyranosyl (1-2)-β-D-galactopyranoside, quercetin 3-O-β-D-xylopyranosyl (1-2)-β-D-glucopyranoside were firstly isolated from H.
    [Show full text]
  • Wo 2008/033466 A2
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date PCT (10) International Publication Number 20 March 2008 (20.03.2008) WO 2008/033466 A2 (51) International Patent Classification: [US/US]; 1750 Washington Street, Boston, MA 021 18 A61K 31/4704 (2006.01) (US). ALTMEYER, RaIf [DE/SG]; 19 Cairnhill Circle, Apartment 17-06, Singapore 229768 (SG). (21) International Application Number: PCT/US2007/019932 (74) Agent: BELLIVEAU, Michael, J.; Clark & Elbing LLP, 101 Federal Street, Boston, MA 021 10 (US). (22) International Filing Date: 13 September 2007 (13.09.2007) (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (25) Filing Language: English AT,AU, AZ, BA, BB, BG, BH, BR, BW, BY,BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, (26) Publication Language: English ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, (30) Priority Data: LR, LS, LT, LU, LY,MA, MD, ME, MG, MK, MN, MW, 60/844,463 14 September 2006 (14.09.2006) US MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, 60/874,061 11 December 2006 (11.12.2006) US PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, (71) Applicant (for all designated States except US): COM- ZM, ZW BINATORX (SINGAPORE) PRE.
    [Show full text]
  • POONAM YADAV Io
    Thesis Entitled SYNTHESIS and characterization OF NEW ox AND NITROGEN HETEROCYCLIC COMPOUNDS WITH ITS BIOLOGICAL AND GROWTH PROMOTING PROPERTIES SUBMITTED TO THE MAHARAJA SAYAJIRAO UNIVERSITY OF BARODA FOR THE DEGREE OF DOCTOR OF PHILOSOPHY IN CHEMISTRY BY POONAM YADAV iO DEPARTMENT OF CHEMISTRY, FACULTY OF SCIENCE THE MAHARAJA SAYAJIRAO UNIVERSITY OF BARODA BARODA - 390 002, INDIA Prof. B.V. Kamath Department of Chemistry*, HEAD & Professor Centre of Advanced Studies in <T* >r% tvs e-mail: Faculty of Science, Vadodara 330 002 kamathbv 1 ©rediffmail.com India Tel: +31 -205-2705552 The Maharaja Sayajirao University of Baroda CHL/ -^3,/P^-D. ll. I APR 2011 CERTIFICATE This is to certify that the work presented in the thesis entitled “Synthesis and Characterization of New Oxygen and Nitrogen Heterocyclic Compounds with its Biological and Growth Promoting Properties”, submitted to the Department of Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, for the award of Ph.D. degree by Ms. Poonam Yadav, is the original research work carried out by her under my guidance and supervision. Dr. Nalini V Purohit (Research Guide) Department of Chemistry, Faculty of Science, The Maharaja Sayajiroa University of Baroda, Vadodara - 390002. Department of Chemistry, Faculty of Science, The Maharaja Sayajiroa University of Baroda, Vadodara - 390002. | J om shree ganeshaya namaha J anant koti brahmand nayak rajadhiraj yogiraj parbrahma shree sachidanand sadguru shree sai nath maharaj kijai anant koti brahmand nayak rajadhiraj yogi raj parbrahma shr sachidanand sadguru shree swami samarth maharaj kijai Jj DECLARATION I state that the work presented in this entitled, “Synthesis and Characterization of New Oxygen and Nitrogen Heterocyclic Compounds with its Biological and Growth Promoting Properties”, comprises of independent investigations carried out by me under the guidance of Dr.
    [Show full text]