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Summary of doctoral thesis: Study on chemical constituents and cytotoxic activity of 3 species allophylus livescens gagnep, chirita halongensis kiew& t.h.nguyen and oldenlandia pinifolia (wa

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Nội dung

The objectives of the thesis: Study on the chemical compositions of three species: Allophylus livescens, Chirita halongesis and Oldenlandia pinifolia growing in Viet Nam to find bioactive compounds as the basis for further research.

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MINISTRY OF EDUCATION

AND TRAINING

VIETNAM ACADEMY

OF SCIENCE AND TECHNOLOGY

GRADUATE UNIVERSITY SCIENCE AND TECHNOLOGY

-

KHIEU THI TAM

STUDY ON CHEMICAL CONSTITUENTS AND CYTOTOXIC

ACTIVITY OF 3 SPECIES ALLOPHYLUS LIVESCENS GAGNEP,

CHIRITA HALONGENSIS KIEW& T.H.NGUYEN AND

OLDENLANDIA PINIFOLIA (WALL EX G.DON) KUNTZE] IN

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This thesis is completed at: Vietnam Academy of Science and

Technology

Scientific instructors:

Assoc Dr NGUYEN THI HOANG ANH

Assoc Dr TRAN VAN LOC

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INTRODUCTION

1 The urgency of the thesis

Today, the economic development, the need for care and protection of the health of the community becomes more urgent Thus, the demand for medicine

in preventing and treatment of incurable diseases especially cancer is increasing

The plant resources in Viet Nam are rich and multiple with over 12000 species of 309 plant families Among them, 3900 species have been used for medicine However, the relationship between the chemical structure and pharmacological activity in many cases has been not clarified

Allophylus livescens and Chirita halongesis, two endemic species of Ha

Long Bay, have not yet studied on chemical compositions and biological

activities Oldenlandia pinifolia is used in traditional medicine for treatment of

inflammation, pain and other diseases and there has been only one report on the phytochemistry of this species

To contribute to understanding, research and systematic evaluation of biologically active compounds from coastal plants and mangroves, and to propose directions for the exploitation and conservation of genetic resources of the rare plant species in Vietnam, we conducted research on the chemical

constituents and cytotoxic activity of 3 species: Allophylus livescens Gagnep.,

Chirita halongesis Kiew & T H Nguyen and Oldenlandia pinifolia (Wall ex

G Don) Kuntze growing in Viet Nam

2 The objectives of the thesis

Study on the chemical compositions of three species: Allophylus

livescens, Chirita halongesis and Oldenlandia pinifolia growing in Viet Nam to

find bioactive compounds as the basis for further research

3 The main contents of the thesis

- Isolation of compounds from three species Allophylus livescens, Chirita

halongesis and Oldenlandia pinifolia collected in Viet Nam by column

chromatography

- Determination of chemical structure of isolated compounds based on

IR, MS, 1D-NMR, 2D-NMR spectroscopic analysis

- Evaluation of cytotoxic activity of extracts and some isolated compounds

4 The contribution of the thesis

This is the first time the chemical constituents and cytotoxic activities of

Allophylus livescens and Chirita halongenis species have been studied in

Vietnam as well as in the world Two compounds were first isolated from

Allophylus genus: 1,6,10,14-phytatetraen-3-ol and catechin Oleanolic acid,

decaffeoylacetoside and β-hydroxy acteoside were found for the first time in

Chirita genus

This is the first study on the cytotoxic activity of Oldenlandia pinofolia

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species in Vietnam and in the world From this species, 14 compounds have

been isolated and structurally elucidated, consisting of a novel compound (1,4,6-trihydroxy-2-methyl-anthraquinone) and two compounds (lutein và

afzelin) isolated for first time from Oldenlandia genus The n-butanol extract

and four isolated compounds inhibited the proliferation of chronic myelogenous leukemia cells, induced apoptosis, and activated caspase 3

(p<0.05)

5 The structure of the thesis

The thesis includes preface (2), contents (131 pages, divided into 4 charptes), conclusion and recommendation (2 pages) There are also list of abbreviations, list of tables, list of figures, published scientific works related to this thesis and references and appendices

THE CONTENT OF THE THESIS

CHAPTER 1: OVERVIEW

1.1 Overview of Allophylus genus

1.1.1 Botanical introduction

1.1.2 Use in traditional medicine

1.1.3 Studied results on the chemical composition and biological activity 1.1.4 Allophylus livescens

Until now, there have been no phytochemical and biological activity work about this species

1.2 Overview of Chirita genus

1.2.1 Botanical introduction

1.2.2 Use in traditional medicine

1.2.3 Study results on the chemical composition and biological activity

1.2.4 Chirita halongensis

Chirita halongensis, an endemic species of Ha Long Bay, detected in the

year 2000 and until now has not been chemically and biologically investigated

1.3 Overview of Oldenlandia genus

1.3.1 Botanical introduction

1.3.2 Use in traditional medicine

1.3.3 Studied results on the chemical composition and biological activity 1.3.4 Oldenlandia pinifolia

Oldenlandia pinifolia (Wall Ex G Don) Kuntze (synonym Hedyotis pinifolia Wall Ex G Don) is a small herb growing in sandy areas from Hue to

the south of Vietnam To the best of our knowledge, there has been only one report on the phytochemistry of this species

1.4 Iridoid compounds

1.4.1 Introduction

1.4.2 Classification

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1.4.3 Biological activity

CHAPTER 2: PLANT METERIALS AND STUDY METHODS

2.1 Plant material and determination of scientific name

- Allophylus livescens Gagnep was collected in Ha Long bay in April 2013 and

determined by Dr Tran Thi Phuong Anh, Vietnam National Museum of Nature,

Vietnam Academy of Science and Technology (VAST) A voucher specimen (No VHH.HL 4.2013.1) was deposited in Institute of Chemistry-Vietnam Academy of Science and Technology (VAST)

- Chirita halongensis Kiew & T.H.Nguyen was collected in Ha Long bay,

Quang Ninh province in October 2013 and determined by Dr Tran Thi Phuong

Anh, Vietnam National Museum of Nature, Vietnam Academy of Science and

Technology (VAST) A voucher specimen (No VHH.HL 10.2013.2) was deposited in Institute of Chemistry-Vietnam Academy of Science and Technology (VAST)

- Oldenlandia pinifolia Wall Ex G Don was collected in Phu Vang, Thua

Thien Hue province in October 2014 and determined by Dr Do Xuan Cam, Hue university A voucher specimen (No VHH.TTH 10.2014.1) was deposited

in Institute of Chemistry-Vietnam Academy of Science and Technology (VAST)

2.2 Methods for treatment and extraction

Leaves, twigs of Allophylus livescens and whole plants of Chirita

halongensis, Oldenlandia pinifolia were extracted by using a general procedure

2.3 Methods for isolation of secondary metabolites

Chromatographic methods: thin layer chromatography (TLC), column chromatography (CC)

2.4 Methods for determination of chemical structure

Spectroscopic methods: Electron Spray Ionisation Mass Spectroscopy (ESI-MS) and High Resolution Electron Spray Ionisation Mass Spectroscopy (HR-ESI-MS), one/two-dimention nuclear magnetic resonance spectra (NMR)

2.5 Methods for biological assays

2.5.1 Cytotoxic activity

The test determined the total cell protein content based on the optical density measured when the cellular protein component was stained with Sulforhodamine B (SRB)

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Allophylus livescens's leaves and twigs

H 2 O aqueous

Figure 3.1 Isolation of compounds from Allophylus livescens

3.1.2 Physical and spectroscopic data of isolated compounds from Allophylus livescens

3.1.2.1 1,6,10,14 Phytatetraen-3-ol (AL1)

Oil, Rf = 0.48 (n-hexane:CH2Cl2 = 95:5, v/v) ESI-MS, m/z = 291

[M+H]+, 1H-NMR (500 MHz, CD3OD): H (ppm) 5.21 (d, 17.5, H-1); 5.05 (d, 11.0, H-1); 5.91 (dd, 10.5 & 17.5; H-2); 1.55 (m, H-4); 1.95 – 2.09 (m, H-5); 5.14 (t, 7.0; H-6); 1.95 – 2.09 (m, H-8, H-9, H-12, H-13); 5.11 (t, 6.5; H-10); 5.11 (t, 6.5, H-14); 1.68 (s, H-16); 1.59 (s, H-17); 1.27 (s, H-18); 1.60 (s, H-19, H-20) 13C-NMR (125 MHz, CD3OD): C (ppm) 111.6 (C-1); 145.1 (C-2); 73.4 (C-3); 42.1 (C-4); 22.7 (C-5); 124.4 (C-6); 135.5 (C-7); 39.7 (C-8); 26.5 (C-9); 124.1 (C-10); 135.0 (C-11); 39.7 (C-12); 26.7 (C-13); 124.2 (C-14); 131.2 (C-15); 25.6 (C-16); 17.6 (C-17); 27.8 (C-18); 16.0 (C-19, C-20)

3.1.2.2 Catechin (AL2)

Orange power, Rf = 0.56 (CHCl3:MeOH:H2O = 6.5:3.5:0.5, v/v) 1H-NMR (500 MHz, CD3OD): H (ppm) 4.60 (d, 7.5 Hz, H-2); 4.00 (m, H-3); 2.53 (dd, 16.0, 8.1 Hz, H-4a); 2.87 (dd, 16.0; 8.1 Hz, H-4b); 5.88 (d, 2.3 Hz, H-6); 5.96 (d, 2.3 Hz, H-8); 6.86 (d, 1.9 Hz, H-2’); 6.79 (d, 8.1 Hz, H-5’); 6.74 (dd, 8.1; 1.9 Hz, H-6’).13C-NMR (125 MHz, CD3OD): C (ppm) 82.8 (C-2); 68.8 (C-3); 28.5 (C-4); 156.9 (C-5); 95.5 (C-6); 157.5 (C-7); 96.3 (C-8); 157.8 (C-9); 100.8 (C-10); 132.2 (C-1’); 115.3 (C-2’); 146.2 (C-3’); 146.2 (C-4’); 116.1 (C-5’); 120.0 (C-6’)

3.1.2.3 Stigmasterol(AL3)

White needles, Rf = 0.55 (n-hexane:EtOAc = 3:1, v/v) 1H-NMR (500

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MHz, CDCl3): H (ppm) 3.51 (m, H-3); 5.34 (m, H-5); 0.92 (d, 6.5 Hz, CH319); 5.01 (dd, 8.5; 15.0 Hz, H-20); 5,15 (dd, 8.5; 15.0 Hz, H-21); 0.84 (t, 7.2

-Hz, CH3-24); 0.83 (d, 6.5 Hz, CH3-26); 0.80 (d, 6.6 Hz, CH3-27); 0.70 (s, CH328); 1.03 (s, CH3-29)

-3.1.2.4 -sitosterol(AL4)

White needles, Rf = 0.55 (n-hexane:EtOAc = 3:1, v/v) 1H-NMR (500 MHz, CDCl3): H (ppm) 3.51 (m, H-3); 5.34 (m, H-5); 0.92 (d, 6.5 Hz, CH3-19); 0.85 (t, 7.2 Hz, CH3-24); 0.83 (d, 6.5 Hz, CH3-26); 0.81 (d, 6.6 Hz, CH3-27); 0.68 (s, CH3-28); 1.02 (s, CH3-29)

3.1.2.5 -sitosterol glucoside (AL5)

White needles, Rf = 0.45 (CH2Cl2:MeOH = 9:1, v/v)

3.2 Isolation of compounds from Chirita halongensis

The whole palnt of Chirita halongensis

H 2 O aqueous CH2

Figure 3.2 Isolation of compounds from Chirita halongensis

3.2.2 Physical and spectroscopic data of isolated compounds from Chirita halongensis

3.2.2.1 7-Hydroxytectoquinone (CH1):

Yellow needles, Rf = 0.30 (CH2Cl2:MeOH = 4.8:0.2, v/v) 1H NMR (500 MHz, CD3OD): H (ppm) 8.07 (brs, H-1); 7.68 (dd, 1.0 & 8.0 Hz, H-3); 8.16 (d, 8.0 Hz; H-4); 8.17 (d, 8.5 Hz, H-5); 7.21 (dd, 2.5 & 8.5 Hz, H-6); 7.59 (d, 2.5

Hz, H-8); 2.54 (s, 2-CH3).13C NMR (125MHz, CD3OD): C (ppm) 128.2 (C-1); 146.3 (C-2); 136.1 (C-3); 128.2 (C-4); 132.8 (C-4a); 130.9 (C-5); 122.3 (C-6);

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164.7 7); 113.5 8); 137.1 8a); 184.6 9); 134.9 9a); 183.3 10); 127.2 (C-10a); 21.8 (2-Me)

Amorphous white power, Rf = 0.3 (n-hexane:EtOAc = 1:1, v/v)

(-)-ESI-MS m/z: 471.0 [M-H]-, molecular formula: C30H48O4 1H-NMR (500 MHz, CDCl3 & CD3OD): H (ppm) 3.83 (br s, H-3); 2.19 (d, 11.0 Hz, H-18); 3.70 (d, 11.0 Hz, Ha-24); 3.46 (d, 11.0 Hz, Hb-24) 13C-NMR (125 MHz, CD3OD): C

(ppm) 34.4 (C-1); 24.5 (C-2); 71.3 (C-3), 44.0 (C-4); 50.6 (C-5); 19.5 (C-6); 34.6 (C-7); 40.9 (C-8); 48.8 (C-9, C-17); 37.9 (C-10); 25.3 (C-11); 126.9 (C-12); 139.6 (C-13); 43.3 (C-14); 29.2 (C-15); 26.1 (C-16); 54.4 (C-18); 40.5 (C-19); 40.4 (C-20); 30.7 (C-21); 38.1 (C-22); 22.8 (C-23); 66.3 (C-24); 16.3 (C-25); 17.6 (C-26); 24.1 (C-27); 181.6 (C-28); 17.7 (C-29); 21.6 (C-30)

3.2.2.3 Ursolic acid (CH3)

Amorphous white power, Rf = 0.5 (CH2Cl2:MeOH = 94:6, v/v)

(-)-ESI-MS m/z: 455.2 [M-H]-, molecular formula: C30H48O3 1H-NMR (500 MHz, CDCl3): H (ppm) 2.98 (m, H-3), 5.11 (m, H-12); 2.09 (d, 11.3 Hz, H-18); 0.88

(s, Me-23); 0.66 (s, Me-24); 0.85 (s, Me-25); 0.73 (s, Me-26); 1.02 (s, Me-27);

0.79 (d, 6.4 Hz, Me-29); 0.89 (d, 8.7 Hz, Me-30) 13C-NMR (125 MHz, CDCl3):

C (ppm)38.2 (C-1); 26.9 (C-2); 76.9 (C-3); 38.4 (C-4); 54.8 (C-5); 18.0 (C-6); 30.2 (C-7); 39.1 (C-8); 47.0 (C-9); 36.5 (C-10); 23.8 (C-11); 124.6 (C-12); 138.2 (C-13); 41.6 (C-14); 32.7 (C-15); 22.8 (C-16); 46.83 (C-17); 52.4 (C-18); 38.4 (C-19); 38.5 (C-20); 27.5 (C-21); 36.3 (C-22); 28.3 (C-23); 16.91 (C-24); 16.1 (C-

25); 15.2 (C-26); 23.3 (C-27); 178.3 (C-28); 17.0 (C-29); 21.1 (C-30)

3.2.2.4 Oleanolic acid (CH4)

Amorphous white power, Rf = 0.48 (CH2Cl2:MeOH = 94:6, v/v)

(-)-ESI-MS m/z: 455.2 [M-H]-, molecular formula: C30H48O3 1H-NMR (500 MHz, CDCl3): H (ppm) 5.27 (1H, t, 3.5 Hz, H-12); 3.20 (1H, dd, 4.0; 11.0 Hz, H-3); 2.81 (1H, dd, 4.0; 13.5 Hz, H-18); 1.12; 0.97; 0.91; 0.90; 0.89; 0.76; 0.74 (each signal 3H, s, Me-23, 24, 25, 26, 27, 29, 30) 13C-NMR (125 MHz, CDCl3): C

(ppm)38.4 (C-1); 27.7 (C-2); 79.1 (C-3); 38.8 (C-4), 55.3 (C-5); 18.3 (C-6); 32.7 (C-7); 39.3 (C-8); 47.7 (C-9); 37.1 (C-10); 23.0 (C-11); 122.7 (C-12); 143.6 (C-13); 41.7 (C-14); 27.2 (C-15); 23.4 (C-16); 46.5 (C-17); 41.1 (C-18); 45.9 (C-19); 30.7 (C-20); 33.8 (C-21); 32.5 (C-22); 28.1 (C-23); 15.6 (C-24); 15.3 (C-25); 17.1 (C-26); 25.9 (C-27); 181.6 (C-28); 33.1 (C-29); 23.6 (C-30)

Amorphous pale yellow power, Rf = 0.3 (EtOAc:MeOH:H2O = 4:0.5:0.1,

v/v) (-)-ESI-MS m/z: 315.0 [M-H]-, molecular formula C14H20O8 1H NMR (500 MHz, CD3OD): H (ppm) 6.71 (d, 1.5 Hz, H-2); 6.69 (d, 8.5 Hz, H-5); 6.57 (dd, 1.5 & 8.5 Hz, H-6); 2.80 (m, H-7); 3.72 (m, H-8); 4.05 (m, H-8); 4.31 (d, 8.0 Hz, Glc-1); 3.20 (t, 8.0 Hz, Glc-2); 3.28 – 3.39 (m, Glc-3, 4, 5); 3.68 (dd,

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5.0 & 12.0 Hz, Glc-6); 3.88 (dd, 1.5 & 12.0 Hz, Glc-6) 13C-NMR (125 MHz,

CD3OD): C (ppm) 131.6 (C-1); 117.1(C-2); 146.1 (C-3); 144.6 (C-4); 116.3 (C-5); 121.3 (C-6); 36.6 (C-7); 72.1 (C-8); 104.4 (Glc-1); 75.1(Glc-2); 77.9 (Glc-3); 71.6 (Glc-4); 78.1 (Glc-5); 62.7 (Glc-6)

3.2.2.6 Acteoside (CH6)

Amorphous power, Rf = 0.56 (CH2Cl2:MeOH:H2O = 3.75:1.0:0.1, v/v)

1

H-NMR (500 MHz, CD3OD): H (ppm) 6.73 (d, 2.0 Hz, H-2); 6.71 (d, 8.0 Hz, H-5); 6.58 (dd, 2.0; 8.5 Hz, H-6); 3.75 (m, H-8); 4.06 (m, H-8); 2.81 (m, H-7);

7.09 (d, J = 1.5 Hz, H-2’); 6.81 (d, 8.0 Hz, H-5’); 6.98 (dd, 1.5 & 8.0 Hz, H-6’);

6.30 (d, 16.0 Hz, H-8’); 7.62 (d, 16.0 Hz, H-7’); 4.40 (d, 8.0 Hz, H-1”); 3.3 – 4.1 (m, H-2”, 3”); 4.95 (t, 9.0 Hz, H-4”); 3.3 – 4.1 (m, H-5”); 5.22 (brs, H-1”’); 3.3 -4.1 (m, H-2”’, H-3”’, H-4”’, H-5”’); 1.12 (d, 6.5 Hz, H-6”’).13C-NMR (125 MHz, CD3OD): C (ppm) 131.5 (C-1); 116.5 (C-2); 144.6 (C-3); 146.0 (C-4); 117.1 (C-5); 121.3 (C-6); 72.3 (C-8); 36.5 (C-7); 127.6 (C-1’); 114.7 (C-2’); 149.7 (C-3’); 146.7 (C-4’); 116.3 (C-5’); 123.2 (C-6’); 168.3 (C-9’); 115.3 (C-8’); 148.0 (C-7’); 104.1 (C-1”); 76.1 (C-2”); 81.6 (C-3”); 70.4 (C-4”); 75.9 (C-5”); 62.3 (C-6”); 103.0 (C-1”’); 72.0 (C-2”’); 72.2 (C-3”’); 73.8 (C-4”’); 70.6 (C-5”’); 18.4 (C-6”’)

3.2.2.7 Isoacteoside (CH7)

Amorphous power, Rf = 0.44 (CH2Cl2:MeOH:H2O = 3.75:1.0:0.1, v/v)

1

H-NMR (500 MHz, CD3OD): H (ppm) 6.70 (d, 1.5 Hz, H-2); 6.67 (d, 8.0 Hz, H-5); 6.55 (dd, 1.5; 8.0 Hz, H-6); 3.73 (m, H-8); 4.05 (m, H-8); 2.80 (m, H-7); 7.06 (d, 2.0 Hz, H-2’); 6.79 (d, 8.0 Hz, H-5’); 6.90 (dd, 2.0 & 8.5 Hz, H-6’); 6.30 (d, 16.0 Hz, H-8’); 7.58 (d, 16.0 Hz, H-7’); 4.33 (d, 8.0 Hz, H-1”); 3.4 – 4.0 (m, H-2”, H-3”, H-4”, H-5”); 4.39 (brt, 5.5 Hz, H-6”); 4.52 (dd, 1.5; 11.5

Hz, H-6”); 5.21 (brs, H-1”’); 3.4 – 4.0 (m, H-2”’, H-3”’, H-4”’,H-5”’); 1.28 (d, 6.0 Hz, H-6”’) 13C-NMR (125 MHz, CD3OD): C (ppm) 131.4 (C-1); 117.1 (C-2); 146.0 (C-3); 144.6 (C-4); 116.4 (C-5); 121.3 (C-6); 72.4 (C-8); 36.6 (C-7); 127.7 (C-1’’); 115.1 (C-2’); 146.7 (C-3’); 149.5 (C-4’); 116.6 (C-5’); 123.2 (C-6’); 169.2 (C-9); 114.8 (C-8’); 147.2 (C-7’); 104.3 (C-1”); 75.3 (C-2”); 84.0 (C-3”); 70.0 (C-4”); 75.6 (C-5”); 64.6 (C-6”); 102.7 (C-1”’); 72.2 (C-2”’); 72.3 (C-3”’); 74.0 (C-4”’); 70.4 (C-5”’); 17.9 (C-6”’)

3.2.2.8 Decaffeoylacteoside (CH8)

Amorphous power, Rf = 0.56 (CH2Cl2:MeOH:H2O = 3.5:1.0:0.1, v/v)

(-)-ESI-MS m/z: 461.0 [M-H]-, molecular formula: C20H30O12 1H-NMR (500 MHz,

CD3OD): H (ppm) 6.71 (d, 1.5 Hz, H-2); 6.69 (d, 8.0 Hz, H-5); 6.57 (dd, 2.0; 8.0 Hz, H-6); 3.72 (m, H-8); 4.01 (m, H-8); 2.80 (m, H-7); 4.31 (d, 8.0 Hz, H-1”); 3.3 – 4.1 (m, H-2”, H-3”, H-4”, H-5”); 3.37 (brt, 9,5 Hz, H-6”); 3.42 (brt, 9.5 Hz, H-6”); 5.17 (d, 1.0 Hz, H-1”’); 3.3 – 4.1 (m, H-2”’, H-3”’, H-4”’, H-

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5”’); 1.26 (d, 7,0 Hz, H-6”’) và 13

C-NMR (125 MHz, CD3OD): C (ppm) 131.5 (C-1); 116.3 (C-2); 144.6 (C-3); 146.1(C-4); 117.1 (C-5); 121.2 (C-6); 72.1 (C-8); 36.5 (C-7); 104.2 (C-1”); 75.6 (C-2”); 84.5 (C-3”); 70.1 (C-4”); 77.8 (C-5”); 62.7 (C-6”); 102.8 (C-1”’); 72.2 (C-2”’); 72.3 (C-3”’); 74.0 (C-4”’); 70.2 (C-5”’); 17.9 (C-6”’)

Amorphous power, Rf = 0.38 (CH2Cl2: MeOH: H2O = 3.5:1.0:0.5, v/v) 1NMR (500 MHz, CD3OD): H (ppm) 6.73 (d, 2.0 Hz, H-2); 6.76 (d, 8.0 Hz, H-5); 6.87 (dd, 2.0; 8.0 Hz, H-6); 3.57 (m, H-8); 4.00 (m, H-8); 4.77 (m, H-7); 7.07 (d, 2.0 Hz, H-2’); 6.80 (d, 8.0 Hz, H5’); 6.98 (dd, 2.0 & 8.0 Hz, H-6’); 6.29 (d, 16.0 Hz, H-8’); 7.62 (d, 16.0 Hz, H-7’); 4.40 (d, 8.0 Hz, H-1”); 3.5 – 4.0 (m, H-2”, H-3”); 4.96 (t, 9.0 Hz, H-4”); 3.5 – 4.0 (m, H-5”); 3.42 (brt, 8.5

Hz, 6”); 3.84 (brt, 9.0 Hz, 6”); 5.22 (brs, 1”’); 3.5 – 4.0 (m, 2”’, 3”’, H-4”’, H-5”’); 1.12 (d, 6.0 Hz, H-6”’) 13

H-C-NMR (125 MHz, CD3OD): C

(ppm) 133.7 (C-1); 114.6 (C-2); 146.3 (C-3); 146.1 (C-4); 116.5 (C-5); 119.0 (C-6); 76.7 (C-8); 74.2 (C-7); 127.7 (C-1’’); 115.3 (C-2’); 146.9 (C-3’); 149.8 (C-4’); 116.2 (C-5’); 123.2 (C-6’); 168.3 (C-9’); 114.7 (C-8’); 148.0 (C-7’); 104.6 (C-1”); 76.4 (C-2”); 81.3 (C-3”); 70.5 (C-4”); 76.1 (C-5”); 62.3 (C-6”); 102.9 (C-1”’); 72.1 (C-2”’); 72.4 (C-3”’); 73.8 (C-4”’); 70.4 (C-5”’); 18.4 (C-6”’)

3.3 Isolation of compounds from Oldenlandia pinifolia

The whole palnt of Oldenlandia pinifolia

H 2 O aqueous HP5

Figure 3.3 Isolation of compounds from Oldenlandia pinifolia

3.3.2 Physical and spectroscopic data of isolated compounds from Oldenlandia pinifolia

3.3.2.1 1,4,6-Trihydroxy-2-methyl-anthraquinone (HP1)

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Orange powder, Rf = 0.45 (n-hexane:CH2Cl2 = 4:1, v/v) HR-ESI-MS: m/z =

3.3.2.3 1,6-Dihydroxy-2-methylanthraquinone (HP3)

Orange powder, Rf = 0.47 (n-hexane:CHCl3:EtOAc = 1.0:1.5:1.0,

v/v).(-)-ESI-MS m/z: 253.0 [M-H]-, molecular formula: C15H10O4 1H-NMR (500 MHz, DMSO-d6): H (ppm) 7.61 (d, 7.5 Hz, H-3); 7.55 (d, 7.5 Hz, H-4); 7.44 (d, 2.5

Hz, H-5); 7.21 (dd, 2.5; 8.5 Hz, H-7); 8.08 (d, 8.5 Hz, H-8); 13.08 ( s, 1-OH); 2.27 (s, 2-CH3) 13C-NMR (125 MHz, DMSO-d6): C (ppm) 159.9 (C-1); 114.6 (C-2); 136.8 (C-3); 118.6 (C-4); 112.5 (C-5); 163.9 (C-6); 121.4 (C-7); 129.8 (C-8); 187.6 (C-9); 181.7 (C-10); 131.1 (C-4a); 124.4 (C-8a); 134.2 (C-9a); 135.6 (C-10a); 15.7 (2-CH3)

3.3.2.4 Digiferruginol (HP4)

Orange-yellow needles, Rf = 0.5 (CH2Cl2: MeOH = 9:1, v/v) (-)-ESI-MS

DMSO-d6), δH (ppm) 7.77 (d, 7.5 Hz, H-3); 7.92 (d, 8.0 Hz, H-4); 8.20 (m, H-5); 7.95

(m, H-6, H-7); 7.92 (m, H-7); 8.25 (m, H-8); 4.66 (d, 5.0 Hz, 2 -CH2OH); 5.46 (t, 5.5 Hz, 2-CH2OH); 12.77 (s, 1-OH) 13C NMR (125 MHz, DMSO- d6), C

(ppm) 158.4 (C-1); 138.2 (C-2); 131.3 (C-3); 118.8 (C-4); 126.8 (C-5); 134.5 (C-6); 135.1 (C-7); 126.6 (C-8); 188.7 (C-9); 181.8 (C-10); 133.6 (C-5a); 133.2 (C-8a); 114.9 (C-9a); 132.8 (C-10a); 57.4 (CH2OH)

3.3.2.5 Lutein(HP5)

Orange-red powder, Rf = 0.44 (n-hexane: EtOAc = 3.75:1.25, v/v) ESI-MS m/z: 569.3 [M+H]+, molecular formula: C40H56O2 1H NMR (500 MHz, CDCl3): H (ppm) 1.48 (t, 12.0 Hz, H2-2); 4.00 (m, H-3); 2.04 (dd, 17.0, 10.0

(+)-Hz, H-4ax); 2.33 – 2.42 ( m, H-4eq); 6.12 (s, H-7, H-8); 6.15 (m, H-10); 6.67 (m, H-11, H-15, H-11’, H-15’); 6.36 (d, 15.0 Hz, H-12); 6.25 (brd, 9.0 Hz, H-14); 1.07 (s, 1-(CH3)2); 1.97 (s, 9-CH3, 13-CH3); 1.37 (dd, 13.0; 7.0 Hz, H-2’ax); 1.84 (dd, 13.0; 6.0 Hz, H-2’eq); 4.25 (m, H-3’); 5.54 (brs, H-4’); 2.33 – 2.42 (m, H-6’); 5.43 (dd, 10.0; 15.5 Hz, H-7’); 6.15 (m, H-8’, H-10’); 6.36 (d, 15.0 Hz, H-12’); 6.25 (brd, 9.0 Hz, H-14’); 0.85 (s, 1’-CH3); 1.00 ( s, 1’-CH3);

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6.58-1.63 (s, 5’-CH3); 1.91 (s, 9’-CH3); 1.97 (s, 13’-CH3) 13C NMR (125 MHz, CDCl3): C (ppm) 37.1 (C-1); 48.5 (C-2); 65.1 (C-3); 42.6 (C-4); 126.2 (C-5); 137.6 (C-6); 125.6 (C-7); 138.5 (C-8); 135.7 (C-9); 131.3 (C-10); 124.8 (C-11); 137.7 (C-12); 136.5 C-13); 132.6 (C-14); 130.1 (C-15); 28.7 (1-Me); 30.3 (1-Me); 21.6 (5 –Me); 12.8 (9-Me, 13-Me); 34.0 (C-1’); 44.6 (C-2’); 65.9 (C-3’); 125.6 (C-4’); 137.8 (C-5’); 55.0 (C-6’); 128.7 (C-7’); 138.0 (C-8’); 135.1 (C-9’); 130.8 (C-10’); 124.5 (11’); 137.6 (C-12’); 136.4 (C-13’); 132.6 (C-14’); 130.0 (C-15’); 24.3 (1’-Me); 29.5 (1’-Me); 22.9 (5’-Me); 14.1 (9’-Me); 13.1 (13’-Me)

White power, Rf = 0.54 (CH2Cl2: MeOH: H2O = 4.0:1.0:0.1, v/v)

(+)-ESI-MS m/z: 437.0 [M+Na]+, molecular formula: C18H22O11 1H NMR (500 MHz, CD3OD): H (ppm) 5.97 (d, 1.0 Hz, H-1); 7.32 (d, 2.0 Hz, H-3); 3.70 (m, H-5); 5.59 (brd, 6.5 Hz, H-6); 5.75 (brs, H-7); 3.32 (m, H-9); 4.69 (dd, 14.0 Hz, 1.0 Hz, H-10a); 4.80 (dd, 14.0, 1.0 Hz, H-10b); 2.10 (s, CH3CO); 4.71 (d, 8.0

Hz, Glc-1); 3.22 (dd, 9.0, 8.0 Hz, Glc-2); 3.31 – 3.40 (m, Glc-3, 4, 5); 3.94 (dd, 12.0, 2.0 Hz, Glc-6); 3.70 (dd, 12.0; 6.0 Hz, Glc-6) 13C NMR (125 MHz,

CD3OD): C (ppm) 93.3 1); 150.3 3); 106.1 4); 37.4 5); 86.3 6); 128.9 (C-7); 144.2 (C-8); 45.2 (C-9); 61.9 (C-10); 172.3 (C-11); 172.6 (CH3CO); 20.6 (CH3CO); 100.0 (Glc-1); 74.6 (Glc-2); 78.3 (Glc-3); 71.6 (Glc-4); 77.8 (Glc-5); 62.8 (Glc-6)

(C-3.3.2.9 Deacetyl asperuloside (HP9)

White power, Rf = 0.67 (CH2Cl2:MeOH = 4:1, v/v) (-)-ESI-MS m/z:

370.9 [M-H]-, molecular formula: C16H20O10 1H NMR (500 MHz, CD3OD): H

(ppm) 5.97 (d, 1.5 Hz, H-1); 7.31 (d, 2.0 Hz, H-3); 3.70 (m, H-5); 5.58 (dd, 1.5; 6.5 Hz, H-6); 5.66 (brs, H-7); 3.32 (m, H-9); 4.21 (brs, H-10); 4.70 (d, 8.0 Hz, Glc-1); 3.21 (dd, 9.0; 8.0 Hz, Glc-2); 3.30 – 3.60 (m, Glc-3, Glc-4, Glc-5); 3.94 (dd, 12.0; 2.0 Hz, Glc-6); 3.84 (dd, 12.0; 6.0 Hz, Glc-6) 13C NMR (125 MHz,

CD3OD): C (ppm) 93.3 1); 150.2 3); 106.5 4); 37.5 5); 86.6 6); 125.7 (C-7); 149.8 (C-8); 45.0 (C-9); 60.1 (C-10); 172.8 (C-11); 99.9 (Glc-1); 74.7 (Glc-2); 78.4 (Glc-3); 71.6 (Glc-4); 77.9 (Glc-5); 62.8 (Glc-6)

(C-3.3.2.10 Asperulosidic acid (HP10)

White power, Rf = 0.56 (CH2Cl2:MeOH = 4:1, v/v) 1H NMR (500 MHz,

CD3OD): H (ppm) 5.07 (d, 9.0 Hz, H-1); 7.63 (s, H-3); 3.05 (m, H-5); 4.85 (m, H-6); 6.04 (brs, H-7); 2.65 (t, 8.0 Hz, H-9); 4.97 (brd, 14.5 Hz, H-10a); 4.83

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