BUI VAN MUOI STUDY ON CHEMICAL CONSTITUENTS OF THREE LICHEN SPECIES OF TWO GENUS PARMOTREMA AND USNEA PhD THESIS OF ORGANIC CHEMISTRY HOCHIMINH CITY, 2024 VIETNAM NATIONAL UNIVERSITY - HO CHI MINH CITY UNIVERSITY OF SCIENCE BUI VAN MUOI STUDY ON CHEMICAL CONSTITUENTS OF THREE LICHEN SPECIES OF TWO GENUS PARMOTREMA AND USNEA Speciality: Organic Chemistry Code: 62 44 01 14 Reviewer 1: PGS. Hà Diệu Ly Reviewer 2: PGS. V6 Thi Nga Reviewer 3: PGS. Lê Tiến Dũng Independent reviewer 1: PGS.
Võ Thi Nga SUPERVISOR 1. NGUYEN KIM PHI PHUNG 2. WARINTHORN CHAVASIRI HOCHIMINH CITY, 2024 DECLARATION The work presented in this thesis was completed in the period of December 2017 to December 2021 under the co-supervision of Professor Nguyen Kim Phi Phung of the University of Science, Vietnam National University, Ho Chi Minh City, Vietnam, and Associate Professor Warinthorn Chavasiri of the Chulalongkorn University, Thailand. In compliance with the university’s regulations, I declare that: 1.
Except where due acknowledgment has been made, the work is that of the author alone; 2. The work has not been submitted previously, in whole or in part, to qualify for any other academic award; 3. The content of the thesis is the result of the work which has been carried out since the official commencement date of the approved postgraduate study program; 4. Ethics procedures and guidelines have been followed.
PhD student BUI VAN MUOI ACKNOWLEDGEMENTS There are many individuals without whom the work described in this thesis might not have been possible, and to whom I am greatly indebted. Firstly, I offer my sincerest gratitude to my supervisor Prof. Nguyen Kim Phi Phung, who has supported me throughout the writing of this thesis with her patience, kindness, invaluable advice, and guidance. I would also like to acknowledge my second supervisor, Prof.
Warinthor Chavasiri for his guidance, patience, and who has taught me the true spirit of research. I am deeply indebted to Assoc. Huynh Bui Linh Chi of Dong Nai University for her teachings, kindness, helpful suggestions, and valuable advice in this research I want to express my sincere thanks to Dr. Vo Thi Phi Giao at the University of Science, Vietnam National University, Ho Chi Minh City, and Dr.
Sipman, Botanic Garden and Botany Museum Berlin-Dahlem, Freie University, Berlin, Germany for their expert assistance in the authenticity of this lichen. Iam very grateful to thank Assoc. Pham Nguyen Kim Tuyen, Assoc. Duong Thuc Huy, and Dr.
Nguyen Tan Phat for giving up their precious time to help me with proofreading some isolated compounds of the thesis. Additionally, I would like to thank my teachers and friends from the Department of Organic Chemistry, Faculty of Chemistry, University of Science, Vietnam National University-Ho Chi Minh City, and students at Dong Nai University for their helpful assistance. Besides, I am also very grateful to thank Vingroup company because I was funded by Vingroup Joint Stock Company and supported by the Domestic PhD Scholarship Programme of Vingroup Innovation Foundation (VINIF), Vingroup Big Data Institute (VINBIGDATA), code VINIF. Finally, an honorable mention goes to my family, especially my parents and wife, for their understanding and support in completing this thesis.
11 LIST OF ABBREVIA TIONS.-- Ánh ng HH Hàng HH nh vn LIST OF TABLES 00. ix LIST OF FIGURES 15177. X LIST OF SCHEMES. - LH nh TH HT HH HH nh nh xii PREFACE ooo.
eecceccssecsecssessecssecscecseessessecsseeseessecseesseesessecsesseessesseeaesseesaeseeeeasenaes xiii CHAPTER 1: LITERATURE REVIEW. HH HH HH re 1 1. PRESENTATION OF LICHENS .- -Q- HH HH HH ie, 1 1. LICHEN SECONDARY METABOLTTTES.2 Shikimic acid pathWAy.
ác TH TH HH HH 12 1.3 Mevalonic acid patWayV/. án HH TT TH HH HH 12 1.- (+ c1 111011911 E910 19119 ng ng rry 13 1. GENERAL INFORMATION OF USNEA CERATINA ARCH, PARMOTREMA PRAESOREDIOSUM (NYL.) HALE, PARMOTREMA TINCTORUM (DESPR. Parmotrema praesorediosum (Nyl.
Parmotrema tinctorum (Despr. CHEMICAL STUDIES ON THE GENUS PARMOTREMA AND USNEA. The lichen genus PArMotre ma. óc vn ng ng nnnưệp 44 1.
cọ TH HH HH HH re 46 1. Cytotoxic and antimutagenic aC{IVI{Y. Antiviral activity and inhibition of viral enZyIm€S. Testing the ability to indicate the level of environmental pollution.
eee eeceecesseeseesseeseceeesecaesseecesseeseesseesaeeeeesaeeneees 54 CHAPTER 2: EXPERIMENTAL SECTION|. INSTRUMENTS AND CHEMICALUS. *S 1H HH TH HH ng HH 57 2. EXTRACTION AND ISOLATION PROCEDURES.
Extraction and isolation on the lichen Usned Ceratind. Extraction and isolation on the lichen Parmotrema praesorediosum. Extraction and isolation on the lichen Parmotrema fÌHICÍOTHIN. LG HH HH HH HH HH TH Hy 66 2.
Cytotoxic vn ốc. œ -Glucosidase inhibition assay. 1v 1v vn kg rey 67 CHAPTER 3: RESULTS AND DISSCUSSIONS. CHEMICAL STRUCTURE ELUCIDATION.
Structure elucidation of compound orcinol (MÏT-]). Structure elucidation of compound atranol (MĨT-2). Structure elucidation of compound orsellinic acid (M T-3). Structure elucidation of compound methyl orsellinate (MT-4).
Structure elucidation of compound methyl Ø-orsellinate (MT-5). Structure elucidation of compound methyl haematommate (MT-6). Structure elucidation of compound methyl (E)-2,4-dihydroxy-6-methy]-3- (3-oxobut-1-en-1-yl)benzoate (MMÏT-7).- -- cv ng re, 79 3. Structure elucidation of compound rhizonic acid (MT-8).
Structure elucidation of compound usneaceratin B (MT-9). Structure elucidation of compound 2-ethylhexyl orsellinate (MT-10). Structure elucidation of compound praesorediosic acid (MT-11). Structure elucidation of compound lecanorin (MT-12).
Structure elucidation of compound gyrophoric acid (MT-13). Structure elucidation of compound atrnorin (MT-14). Structure elucidation of compound diffractaic acid (MT-15). Depsid one oo.
Structure elucidation of compound stictic acid (MT-16). Structure elucidation of compound 8’-O-methylstictic acid (MT-17). Structure elucidation of compound 8’-O-ethylstictic acid (MT-18). Structure elucidation of compound ceratinalone (MT-19).
Structure elucidation of compound tinctorinone (MT-20). Structure elucidation of compound bailesdone (MT-2T). Structure elucidation of compound ceratinepone (MT-22). Structure elucidation of compound virensic acid (MT-23).
Structure elucidation of compound protocetraric acid (MT-24). Structure elucidation of compound 9’-O-methylprotocetraric acid (M[T-25). ---- << Set k HH He, 117 3. Structure elucidation of compound praesorether E (MT-26).
Structure elucidation of compound praesorether D (MT-27). Structure elucidation of compound (+)-12R-usnic acid (MT-28). Structure elucidation of compound (+)-12R-isousnic acid (MT-29). Structure elucidation of compound usneaceratin A (MT-30).
Compounds of other types. TH TH ng ng ng ngệt 130 3. Structure elucidation of compound sernanderin (MT-31). Structure elucidation of compound hopane-6a, 16/,22-triol (MT-32).
Structure elucidation of compound palmitic acid (MT-33). Structure elucidation of compound uracil (MT-34). 2 t1 1S HH HH HH Hy kệ, 137 3. Cytotoxic activity against three cancer Cell ]ines.
a-Glucosidase inhibition assay. BIOSYNTHESIS OF ISOLATED COMPOUNDS IN LICHENS. CHEMICAL CONSTITUENTS OF THE THREE LICHENS. SG LH HH HT TH TH HH ng 160 4.
161 LIST OF PUBLICATIONS .- ng TH TH ng TH nh nh TH ng 162 ;35)85)45)) ®ìs`ƒHtidỞÝỞỞỐ. 182 vii LIST OF ABBREVIATIONS 1D One dimensional 2D Two dimensional Ac Acetone APCI-MS Atmospheric pressure chemical ionisation mass spectrometry. ATP Adenosine triphosphate br Broad C Chloroform calcd Calculated CC Column chromatography COSY Homonuclear shift correlation spectroscopy d Doublet dd Doublet of doublets dt Doublet of triplets DMSO Dimethyl sulfoxide EA Ethyl acetate ECD Experimental electronic circular dichroism spectrum. EI-MS Electron-impact ionization mass spectrum H n-Hexane HMBC Heteronuclear multiple bond correlation spectroscopy HR-ESIMS High resolution electrospray ionization mass spectrum HSQC Heteronuclear single quantum correlation spectroscopy m Multiplet min Minutes Me Methanol MS Mass spectrum NAD* Nicotinamide adenine dinucleotide NMR Nuclear magnetic resonance NOESY Nuclear overhauser enhancement spectroscopy viii ppm Parts per million (chemical shift value) pre TUC Preparative thin-layer chromatography q Quartet S Singlet t Triplet SAM S adenosyl-]-methionine CYP450 is a system consisting of 50 enzymes belonging to the monooxygenase group.
TLC Thin-layer chromatography UV Ultraviolet ICso Half-maximal inhibitory concentration ix LIST OF TABLES Table 1.1: Antibacterial activity 45 Table 1.2: Antifungal activity 47 Table 1.3: Cytotoxic and antimutagenic activity 49 Table 1.4: Antiviral activity and inhibition of viral enzymes 51 Table 1.5: Enzymes are inhibited by lichen compounds 52 Table 1.6: Studies on Vietnamese lichens 55 Table 3.1: The NMR data of (MT-1-MT-6) 72 Table 3.2: The NMR data of (MT-7-MT-11) 82 Table 3.3: The NMR data of MT-12-MT-15) 92 Table 3.4: The NMR data of MT-16—-MT-21) 100 Table 3.5: The NMR data of (MT-22-MT-25) 115 Table 3.6: The NMR data of (MT-26—-MT-27) 122 Table 3.7: The NMR data of (MT-28-MT-29) 125 Table 3.8: The NMR data of (MT-30) 130 Table 3.9: The NMR data of (MT-31-MT-34) 133 Table 3. % Inhibition of cytotoxic activity against four cancer cell lines of isolated compounds 137 Table 3. % Inhibition of cytotoxic activity against four cancer cell lines of some compounds in other lichens 139 Table 3. ICso of cytotoxic activity against four cancer cell lines of diffrataic acid, ceratinalone and 8’-O-methylstictic acid.
ICso of cytotoxic activity against four cancer cell lines of of some compounds in other lichens. % Inhibition and ICso of the a-glucosidase inhibition of isolated compounds 145 LIST OF FIGURES Figure 1.1: Types of lichens 1 Figure 1.2: Biosynthetic pathways of lichen secondary metabolites 3 Figure 1.3: Monocyclic aromatic compounds 4 Figure 1. Diphenyl ethers 8 Figure 1. Aliphatic acids 10 Figure 1.
Quinones, chromones and xanthones 11 Figure 1.11: Puvinic acid derivatives 12 Figure 1.12: Two common triterpenenoid skeletons 12 Figure 1.13: Some N-containing compounds 13 Figure 1.14: Usnea ceratina Arch 15 Figure 1.15: Parmotrema praesorediosum (Nyl.16: Parmotrema tinctorum (Despr.1: Chemical structures of compounds (MT-1-MT-11) 70 Figure 3.2: The chemical structure and HMBC correlations of (MT-3) 74 Figure 3.3: The chemical structure and HMBC correlations of (MT-5) 77 Figure 3.4: The chemical structure and HMBC correlations of (MT-6) 79 Figure 3.5: The chemical structure and HMBC correlations of (MT-7) 81 Figure 3.6: The chemical structure and HMBC correlations of (MT-8) 84 Figure 3.7: The chemical structure and HMBC correlations of (MT-9) 85 Figure 3.8: The HMBC correlations of (MT-10) 87 Figure 3.9: The chemical structure and HMBC correlations of (MT-11) 89 xi Figure 3.10: Chemical structures of compounds (MT-12, 13, 14 and 15) 89 Figure 3.11: The HMBC correlations of (MT-12) 91 Figure 3.12: The HMBC correlations of (MT-13) 93 Figure 3.13: The HMBC correlations of (MT-14) 95 Figure 3.14: The HMBC correlations of (MT-15) 97 Figure 3.15: Chemical structures of compounds (MT-16-MT-24) 98 Figure 3.16: The HMBC correlations of (MT-17) 102 Figure 3.17: The HMBC correlations of (MT-18) 104 Figure 3.18: The HMBC correlations of (MT-19) 106 Figure 3.19: Thin layer chromatography of (MT-18 and MT-19) 108 Figure 3.20: The HMBC correlations of (MT-20) 109 Figure 3.21: The HMBC correlations of (MT-21) 112 Figure 3.22: The HMBC correlations of (MT-22) 113 Figure 3.23: The HMBC correlations of (MT-25) 118 Figure 3.24: Chemical structures of compounds MT-26—MT-27 119 Figure 3.25: The HMBC correlations of (MT-26) 121 Figure 3.26: The HMBC correlations of (MT-27) 124 Figure 3.27: Chemical structures of compounds MT-28-MT-30 125 Figure 3.28: The HMBC correlations of (MT-29) 127 Figure 3.29: The chemical structure and HMBC correlations of (MT-30) 129 Figure 3.30: Chemical structures of compounds MT-31-MT-34 130 Figure 3.31: The HMBC correlations of (MT-31) 132 Figure 3.32: The chemical structure and HMBC correlations of (MT-32) 134 Figure 3.33: The chemical structure and HMBC correlations of (MT-34) 136 Figure 3.34: Biosynthesis of monocyclic compounds 147 Figure 3.35: Biosynthesis of monocyclic compounds (cont) 148 Figure 3.36: Biosynthesis of MT-14 149 Figure 3.37: Biosynthesis of MT-12 and MT-15 150 Figure 3.38: Biosynthesis of dibenzofurans 151 xii Figure 3.39: Biosynthesis of depsidone 152 Figure 3.40: Biosynthesis of MT-19, 21 and 22 154 Figure 3.41: Biosynthesis of MT-10 155 LIST OF SCHEMES Scheme 1: Procedure for isolation of compounds from Usnea ceratina Arch 63 Scheme 2: Procedure for isolation of compounds from Parmotrema praesorediosum (Nyl.) Hale 64 Scheme 3: Procedure for isolation of compounds from Parmotrema tinctorum (Despr.) Hale 65 xiii PREFACE The lichen is a dual organism consisting of a fungus and a photosynthetic algae or cyanobacteria which live in close association. There are more than 1700 species of lichen in the world.! 106] Tichens can grow on soil, stone, bark, and leaf in harsh environmental conditions from temperate zones to tropics." Lichens and lichen products have been used in traditional medicines. The action of lichen-derived compounds on tumor cells has been a focus of evaluations for some decades.