Chemical constituents of borreria alata AUBL DC RUBIACEAE

VIETNAM NATIONAL UNIVERSITY - HO CHI MINH CITY UNIVERSITY OF SCIENCE  TÔ CẨM LOAN CHEMICAL CONSTITUENTS OF BORRERIA ALATA (AUBL.) DC (RUBIACEAE) MASTER’S THESIS IN ORGANIC CHEMISTRY Ho Chi Minh City - 2014 VIETNAM NATIONAL UNIVERSITY - HO CHI MINH CITY UNIVERSITY OF SCIENCE  TÔ CẨM LOAN CHEMICAL CONSTITUENTS OF BORRERIA ALATA (AUBL.) DC (RUBIACEAE) Subject: Organic chemistry Code number: 60 44 27 MASTER’S THESIS IN ORGANIC CHEMISTRY SUPERVISOR: PROF NGUYỄN KIM PHI PHỤNG Ho Chi Minh City - 2014 CHEMICAL CONSTITUENTS OF BORRERIA ALATA (AUBL.) DC (RUBIACEAE) By TÔ CẨM LOAN A thesis submitted in partial fulfillment of the requirements For the completion of MASTER OF SCIENCE Department of Organic Chemitry University of Science, VN National University - HCM City 2014 Examination Board: Chairman : Ass Prof Dr Nguyễn Trung Nhân 1st Reviewer : Dr Phạm Nguyễn Kim Tuyến 2nd Reviewer : Dr Võ Thị Ngà Secretarial member : Dr Tôn Thất Quang Supervisor : Prof Dr Nguyễn Kim Phi Phụng ĐẠI HỌC QUỐC GIA THÀNH PHỐ HỒ CHÍ MINH TRƯỜNG ĐẠI HỌC KHOA HỌC TỰ NHIÊN  TƠ CẨM LOAN KHẢO SÁT THÀNH PHẦN HĨA HỌC CÂY BORRERIA ALATA (AUBL.) DC (RUBIACEAE) CHUYÊN NGÀNH : HÓA HỮU CƠ MÃ SỐ : 60.44.27 NGƯỜI HƯỚNG DẪN KHOA HỌC: GS.TS NGUYỄN KIM PHI PHỤNG T H Ch M nh - 2014 TÓM TẮT Borreria alata (Aubl.) DC (hay Spermacoce alata Aubl., B latifolia K Schum.) phổ biến vùng nhiệt đới cận nhiệt Châu Mỹ, Châu Phi, Châu Âu Châu Á Ở Nepal, rễ Borreria alata dùng để chữa bệnh sốt rét Trên giới có nghiên cứu Borreria alata thu hái Indonesia Trong nghiên cứu này, hợp chất iridoid glycosid hợp chất diterpenoid cô lập Ở Việt Nam, Borreria alata dùng làm phủ đất chưa có nghiên cứu thành phần hóa học hoạt tính sinh học Bằng phương pháp chiết tách cô lập sắc ký cột silica gel, sắc ký lớp mỏng…8 hợp chất BA3 (Kaempferol), BA4 (Ursolic acid), BA6 (Vomifoliol 9O-β-D-glucopyranoside), BA7 (7β-hydroxy-11-methylforsythide), BA9 (Sodium deacetylasperulosidate), BA14 (Oleanolic acid), BA10 (Sodium loganate) and BA15 (3β,6β,23-trihydroxyurs-12-en-28-oic acid) cô lập từ Borreria alata thu hái huyện Di Linh, tỉnh Lâm Đồng Trong đó, BA4, BA6, BA14 lần cô lập Borreria alata; BA3, BA7, BA9, BA15 lần biết đến chi Borreria; BA10 hợp chất Cấu trúc hợp chất xác định thông qua phổ NMR, phổ khối so sánh với tài liệu công bố i ABSTRACT Eight compounds, kaempferol (BA3), ursolic acid (BA4), oleanolic acid (BA14), 3β,6β,23-trihydroxyurs-12-en-28-oic acid (BA15), vomifoliol 9-O- -Dglucopyranoside (BA6), 7β-hydroxy-11-methylforsythide (BA7), sodium deacetylasperulosidate (BA9) and sodium loganate (BA10) were isolated from the chloroform extract and the methanol extract of the whole plant of Borreria alata (Aubl.) DC., which was collected in Lam Dong province These isolated compounds were known for the first time in Borreria alata Among them, three compounds BA4, BA6, BA14 were already known in other herbs of Borreria, four compounds BA3, BA7, BA9, BA15 were known for the first time in this genus BA10 is a new compound The chemical structure of the isolated compounds was elucidated by spectroscopic methods as well as comparison of their NMR data with those in the literature ii ACKNOWLEDGEMENTS First of all, I would like to express my gratitude to all those who supported me throughout the writing of this graduation assignment I am deeply indebted to my research supervisor Prof Nguyen Kim Phi Phung, Department of Organic Chemistry, Faculty of Chemistry, University of Science, for her dedicated instruction as well as her devoted assitance along with invaluable advice and encouragement over the past years My thanks are also due to Botanist Vo Van Chi who helped me to identify the scientific name of the plant Borreria alata (Aubl.) DC collected in Lam Dong Province In addition, I want to give my sincere thanks to Assoc Prof Nguyen Trung Nhan, Dr Pham Nguyen Kim Tuyen, Dr Vo Thi Nga and Dr Ton That Quang of the thesis committee for their precious and valuable comments for the completion of this thesis I would also like thank my lab colleagues who helped me in the process of my study Last but not the least, I would like to express my warm thanks to my family, especially my husband, for their consistent encouragement and support throughout the writing of this final assignment TÔ CẨM LOAN iii TABLE OF CONTENTS CONTENT Page ABSTRACT i ACKNOWLEDGEMENTS iii TABLE OF CONTENTS iv LIST OF ABBREVIATIONS vi LIST OF TABLES viii LIST OF FIGURES AND SCHEMES ix Chapter GENERAL INTRODUCTION 1.1 General information of Borreria 1.2 Generic description of Borreria alata 1.3 Pharmacological studies of some Borreria species 1.3.1 Borreria alata (Aubl.) DC 1.3.2 Borreria articularis (L f.) 1.3.3 Borreria centranthoides Cham and Schltdl 1.3.4 Borreria eupatorioides Cham and Schltdl 1.3.5 Borreria hispida (Linn.) K Schum 1.3.6 Borreria laevis (Lam.) Griseb 1.3.7 Borreria ocymoides (Burm f.) DC 1.3.8 Borreria princeae K Schum 1.3.9 Borreria pusilla (Wall.) DC 1.3.10 Borreria verticillata (L.) G F W Mey 1.4 Chemical studies of some Borreria species Chapter EXPERIMENTAL 2.1 General Experimental Procedures 16 2.2 Plant material 16 2.3 Extraction and Isolation 16 iv Chapter RESULTS & DISCUSSION 3.1 Structure elucidation of Compound BA3 23 3.2 Structure elucidation of Compound BA4 25 3.3 Structure elucidation of Compound BA14 27 3.4 Structure elucidation of Compound BA15 29 3.5 Structure elucidation of Compound BA6 32 3.6 Structure elucidation of Compound BA7 35 3.7 Structure elucidation of Compound BA9 39 3.8 Structure elucidation of Compound BA10 44 Chapter CONCLUSION 49 REFERENCES 51 LIST OF PUBLICATION 59 APPENDICES v LIST OF ABBREVIATIONS B : Borreria S : Spermacoce 1D/2D-NMR : One/Two Dimensional – Nuclear Magnetic Resonance brd : Broad doublet brs : Broad singlet brt CC : Broad triplet : Column chromatography COSY : Correlation spectroscopy d : Doublet dd DMSO : Doublet of doublet : Dimethylsulfoxide DEPT : Distortionless Enhancement by Polarization Transfer HSQC : Heteronuclear Single Quantum Correlation HMBC : Heteronuclear Multiple Bond Coherence HPLC : High Performance Liquid Chromatography J : Coupling constant lit : Literature LC-MS : Liquid Chromatography - Mass Spectrometry m m/z : Multiplet : Mass to charge ratio MeOH : Methanol ppm : Part per million Rf s : Retardation factors : Singlet TLC : Thin layer chromatography t : Triplet UV : Ultraviolet [α]D o C : Specific rotation : Degree Celcius Glc : Glucose vi BA7-CD3OD-COSY Appendix 17: COSY spectrum of BA7 COOCH3 11 H HO OH 4' HO HO 6' H HOOC 10 O 5' O 2' 3' 1' OH O BA7-CD3OD-HSQC Appendix 18: HSQC spectrum of BA7 COOCH3 11 H HO -OCH3 OH 4' HO HO 6' H HOOC 10 O 5' O 2' 3' 1' OH O BA7-CD3OD-HMBC Appendix 19: HMBC spectrum of BA7 COOCH3 11 H -OCH3 HO OH 4' 6' H HOOC 10 O O 5' HO HO 2' 3' 1' OH O BA9-CD3OD-1H Appendix 20: 1H spectrum of BA9 11 HO COONa H OH HO 4' H 6' O 5' HO HO O 2' 3' 1' OH O BA9-CD3OD-1H Appendix 20a: 1H spectrum of BA9 11 HO COONa H OH HO 4' H 6' O 5' HO HO O 2' 3' 1' OH O BA9-CD3OD-13C Appendix 21: 13C spectrum of BA9 11 HO COONa H OH HO 4' H 6' O 5' HO HO O 2' 3' 1' OH O BA9-CD3OD-13C Appendix 22: 13C spectrum of BA9 11 HO COONa H OH HO 4' H 6' O 5' HO HO O 2' 3' 1' OH O BA10-CD3OD-1H Appendix 24: 1H spectrum of BA10 COONa 11 H HO OH 6' O 5' HO HO O H 10 4' O 2' 3' 1' OH -CH3 BA10-CD3OD-d4-1H Appendix 24a: 1H spectrum of BA10 COONa 11 H HO OH H 10 4' 6' O 5' HO HO O 2' 3' 1' OH O BA10-CD3OD-13C Appendix 25: 13C spectrum of BA10 COONa 11 H OH H 10 4' 6' O 5' HO HO HO O 2' 3' 1' OH O BA10-CD3OD-d4-COSY -CH3 Appendix 26: COSY spectrum of BA10 COONa 11 H -CH3 OH H 10 4' 6' O 5' HO HO HO O 2' 3' 1' OH O BA10-CD3OD-HSQC -CH3 Appendix 27: HSQC spectrum of BA10 -CH3 COONa 11 H OH H 10 4' 6' O 5' HO HO O 2' 3' 1' OH 3 HO O BA10-CD3OD-HMBC -CH3 Appendix 28: HMBC spectrum of BA10 -CH3 COONa 11 H OH H 10 4' 6' O 5' HO HO HO O 2' 3' 1' OH O BA9-HR-ESI-MS 11 HO COONa H [C16 H21 O11 Na+H]+ [C16 H21 O11 Na+Na]+ 4' O OH HO H 6' O 5' HO HO O 2' 3' 1' OH 11 HO COONa [C16 H21 O11 Na+H]+ H OH HO 4' 6' O 5' HO HO O H O 2' 3' 1' OH Appendix 23: Mass spectrum of BA9 BA10-HR-ESI-MS COONa 11 H HO O OH H [C16 H23 O10 Na+Na]+ 10 6' 4' [C16 H23 O10 Na+H]+ O 5' HO O 2' 3' HO 1' OH 11 COONa H HO [C16 H23 O10 Na+H]+ OH O H 10 4' 6' O 5' HO O 2' HO 3' 1' OH Appendix 29: Mass spectrum of BA10 ... Dong Province Borreria alata (Aubl. ) DC 1.3 Literature review Pharmacological studies of some Borreria species 1.3.1 Borreria alata (Aubl. ) DC B alata (Aubl. ) DC [Syn.: S alata (Aubl. ), B latifolia... information of Borreria 1.2 Generic description of Borreria alata 1.3 Pharmacological studies of some Borreria species 1.3.1 Borreria alata (Aubl. ) DC 1.3.2 Borreria articularis (L f.) 1.3.3 Borreria. .. City - 2014 CHEMICAL CONSTITUENTS OF BORRERIA ALATA (AUBL. ) DC (RUBIACEAE) By TÔ CẨM LOAN A thesis submitted in partial fulfillment of the requirements For the completion of MASTER OF SCIENCE