University of South Florida Scholar Commons Graduate Theses and Dissertations Graduate School 3-19-2004 Chemical Investigation of Three Antarctic Marine Sponges Young Chul, Park University of South Florida Follow this and additional works at:https://scholarcommons.usf.edu/etd Part of theAmerican Studies Commons Scholar Commons Citation Park, Young Chul,, "Chemical Investigation of Three Antarctic Marine Sponges" (2004).Graduate Theses and Dissertations. https://scholarcommons.usf.edu/etd/1190 This Dissertation is brought to you for free and open access by the Graduate School at Scholar Commons. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Scholar Commons. For more information, please contact [email protected]. Chemical Investigation of Three Antarctic Marine Sponges by Young Chul Park A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy Department of Chemistry College of Arts and Sciences University of South Florida Major Professor: Bill J. Baker, Ph.D Robert Potter, Ph.D Edward Turos, Ph.D Abdul Malik, Ph.D Date of Approval: March 19, 2004 Keywords: marine natural products, tryptophan catabolism, chemical defense, Antarctic invertebrates, erebusinone © Copyright 2004, Young Chul Park DEDICATION This dissertation is dedicated to my wife Jung Sook, who never fails to remind me how every day is most precious. I would also like to dedicate this work to my daughter, Yei Ryun and my son, Min Jun. I would like to dedicate this work to my dear parents, who gave me their love and patience. I would also like to dedicate this work to my father-in-law and my mother-in-law, for their patience and understanding on the value of education. Without their support, love, and patience, there is no way I could possibly have accomplished this. ACKNOWLEDGMENTS First and foremost, I would like to acknowledge my adviser, Dr. Bill J. Baker. This dissertation would not have been possible without his assistance and financial support. He has taught, inspired, and challenged me throughout this process. I would like to thank Jill Baker, for her concern towards my family. I would like to thanks Dr. James B. McClintock and Dr. Charles D. Amsler at the University of Alabama at Birmingham for the field and laboratory assistance. I would like to thank Dr. Steven Mullen at the University of Illinois at Urbana- Champaign, for the mass spectral data. Also I would like to thank Dr. Maya. P. Singh from Wyeth Pharmaceuticals and Dr. Fred Valeriote from Ford hospital for their bioactivity data. Finally, I would like to acknowledge my committee members, Dr. Robert Potter, Dr. Edward Turos and Dr. Abdul Malik, for their encouragement and guidance. Last but not the least I would like to thank Dr. Baker’s students who have given me assistance in many ways. TABLE OF CONTENTS LIST OF FIGURES v LIST OF TABLES xvi LIST OF SCHEMES xviii LIST OF ABBREVIATIONS xvix ABSTRACT xxii CHAPTER 1. INTRODUCTION 1 1.1 A Brief History of Natural Products 1 1.2 Marine Natural Products Chemistry 1 1.3 Antarctic Marine Natural Products 8 1.4 Research Objectives 11 CHAPTER 2. CHEMICAL INVESTIGATION OF ANTARCTIC MARINE SPONGE ISODICTYA ERINACEA 12 2.1 Introduction 12 2.2 Extraction and Isolation of Secondary Metabolites 14 2.3 Characterization of Purine analog (23) 16 2.4 Characterization of 3-Hydroxykynurenine (24) 20 CHAPTER 3. CHEMICAL INVESTIGATION OF ANTARCTIC MARINE SPONGE ISODICTYA SETIFERA 25 3.1 Introduction 25 3.2 Extraction and Isolation of Secondary Metabolites 26 3.3 Characterization of 5-methyl-2’-deoxycytidine (25) 28 i 3.4 Characterization of Uridine (28) 33 3.5 Characterization of 2’-Doxycytidine (31) 37 3.6 Characterization of 4, 8-Dihydroxyquinoline (33) 42 3.7 Characterization of Homarine (37) 46 CHAPTER 4. CHEMICAL INVESTIGATION OF ANTARCTIC MARINE SPONGE ISODICTYA ANTARCTICA 50 4.1 Extraction and Isolation of Secondary Metabolite 50 4.2 Characterization of Ceramide analog (39) 52 4.3 Determination of Stereochemistry 61 CHAPTER 5. TOTAL SYNTHESIS OF NATURAL PRODUCT EREBUSINONE AND EREBUSINONAMINE 70 5.1 Introduction 70 5.2 Synthesis of Erebusinone (12) 74 5.3 Results and Discussion 74 5.4 The synthesis of Erebusinonamine (52) 77 5.5 Results and Discussion 77 CHAPTER 6. BIOASSAY OF PURE COMPOUNDS 79 CHAPTER 7. DISCUSSION 81 ii CHAPTER 8. EXPERIMENTAL 84 8.1 General Procedure 84 8.2 Isolation of Secondary Metabolites from Isodicyta erinacea 86 8.2.1 Spectral data of Purine analog (23) 87 8.2.2 Spectral data of 3-Hydroxykynurenine (24) 88 8.3 Isolation of Secondary Metabolites from Isodictya setifera 89 8.3.1 Spectral data of 5-Methyl-2’-deoxycytidine (25) 90 8.3.2 Spectral data of Uridine (28) 91 8.3.3 Spectral data of 2’-Doxycytidine (31) 92 8.3.4 Spectral data of 4, 8-Dihydroxyquinoline (33) 93 8.3.5 Spectral data of Homarine (37) 94 8.4 Isolation of Secondary Metabolite from Isodictya antarctica 95 8.4.1 Spectral data of Ceramide analog (39) 96 8.4.2. Methanolysis of Ceramide analog (39) 97 8.4.3 Preparation of MTPA esters for Ceramide analog (39) 98 8.4.3.1 (S) - MTPA Ester (43) 98 8.4.3.2 (R) - MTPA Ester (44) 99 8.5. Synthesis of Erebusinone (12) 100 8.5.1 Preparation of Benzyl-3-(benzyloxy)-2-nitrobenzoate (46) 100 8.5.2 Preparation of 3-[3-(Benzyloxy)-2-nitrophenyl]-3- oxopropanenitrile (47) 101 8.5.3 Preparation of 3-[3-(Benzyloxy)-2-nitrophenyl]-3-hydroxy propanenitrile (48) 102 iii 8.5.4 Preparation of 3-Amino-1-[3-benzyloxy-2-nitrophenyl]- propan-1-ol (49) 103 8.5.5 Preparation of N-{3-[3-(Benzyloxy)-2-nitrophenyl]-3-hydroxypropyl} acetamide (50) 104 8.5.6 Preparation of N-{3-[3-(Benzyloxy)-2-nitrophenyl]-3-oxopropyl} acetamide (51) 105 8.5.7. Preparation of Erebusinone, N-[3-(2-amino-3-hydroxyphenyl)- 3-oxopropyl] acetamide (12) 106 8.6 Synthesis of Erebusinonamine (52) 107 8.6.1 Preparation of tert-Butyl-3-[3-(benzyloxy)-2-nitrophenyl]-3- hydroxypropylcarbamate (53) 107 8.6.2. Preparation of tert-Butyl-3-[3-(benzyloxy)-2-nitrophenyl]-3- oxopropyl carbamate (54) 108 8.6.3. Preparation of 3-Amino-1-[3-(benzyloxy)-2-nitrophenyl]- propan-1-one hydrochloride (55) 109 8.6.4. Preparation of Erebusinonamine, 3-Amino-1-(2-amino-3- hydroxyphenyl)propan-1-one hydrochloride (52) 110 REFERENCES 111 APPENDICES 119 ABOUT THE AUTHOR End Page iv LIST OF FIGURES Figure 1. Isodictya erinacea collected from at Erebus Bay, Ross Island, Antarctica 12 Figure 2. 1H NMR spectrum of purine analog (23) (500 MHz, DMSO-d ) 16 6 Figure 3. 13NMR spectrum of purine analog (23) (125 MHz, DMSO-d ) 17 6 Figure 4. gHMBC spectrum of purine analog (23) (500 MHz, DMSO-d ) 18 6 Figure 5. Key gHMBC correlations of observed in purine analog (23) 18 Figure 6. 1H NMR spectrum of 3-hydroxykynurenine (24) (250 MHz, MeOH-d ) 21 4 Figure 7. 1H NMR spectrum of synthetic erebusinone (12) (250 MHz, MeOH-d ) 21 4 Figure 8. 13C NMR spectrum of 3-hydroxykynurenine (24) (125 MHz, DMSO-d ) 22 6 Figure 9. gHMBC spectrum of 3-hydroxykynurenine (24) (500 MHz, DMSO-d ) 23 6 Figure 10. Key gHMBC correlations observed in 3-hydroxykynurenine (24) 23 Figure 11. Assigned NMR data of erebusinone and 3-hydroxykynurenine (MeOH-d , 1H 4 NMR 250 MHz; 13C NMR, 75, 125 MHz) * 1H chemical shifts 24 Figure 12. Isodictya setifera collected from Bahia Paraiso, Palmer Station, Antarctica 25 Figure 13. 1H NMR spectrum of 5-Methyl-2’-deoxycytidine (25) (500 MHz, MeOH-d ) 28 4 Figure 14. 13C NMR spectrum of 5-Methyl-2’-deoxycytidine (25) (125 MHz, MeOH-d ) 29 4 Figure 15. gCOSY correlations of 25 30 Figure 16. gHMBC spectrum of 5-Methyl-2’-deoxycytidine (25) (500 MHz, MeOH-d ) 31 4 Figure 17. Key gHMBC correlations observed in 5-methyl-2’-deoxycytidine (25) 31 v Figure 18. Assigned 1H NMR chemical shifts (δ) of 5-methyl-2’-deoxycytidine 25 (500 MHz, MeOH-d ) from the current study data, 2-deoxycytidine 26 4 and thymidine 27 (D O, 120 MHz) 32 2 Figure 19. 1H NMR spectrum of uridine (28) (500 MHz, DMSO-d ) 33 6 Figure 20. gCOSY correlations of uridine 28 34 Figure 21. 13C NMR spectrum of uridine (28) (125 MHz, DMSO-d ) 35 6 Figure 22. gHMBC spectrum of uridine (28) (500 MHz, DMSO-d ) 35 6 Figure 23. Key gHMBC correlations observed in uridine (28) 36 Figure 24. Assigned 1H NMR chemical shifts (δ) of uridine 28 (500 MHz, DMSO-d ) 6 from the current study data, previous reported uridine 29 and uridine 30 (100 MHz, D O + NaOD) 37 2 Figure 25. 1H NMR spectrum of 2’-deoxycytidine (31) (500 MHz, DMSO-d ) 38 6 Figure 26. gCOSY correlations of 31 38 Figure 27. 13C NMR spectrum of 2’-deoxycytidine (31) (125 MHz, DMSO-d ) 39 6 Figure 28. gHMBC spectrum of 2’-deoxycytidine (31) (500 MHz, DMSO-d ) 40 6 Figure 29. Key gHMBC correlations observed in 2’-deoxycytidine (31) 40 Figure 30. Assigned 1H NMR chemical shifts (δ) of natural 2-deoxycytidine 31 (500 MHz, DMSO-d ) from the current study data, previous reported 2- 6 deoxycytidine 32 (MeOH-d , 360 MHz) and authentic sample 26 4 (100 MHz, D O + NaOD) 42 2 Figure 31. 1H NMR spectrum of 4, 8-dihydroxyquinoline (33) (500 MHz, DMSO-d ) 43 6 Figure 32. 13C NMR spectrum of 4, 8-Dihydroxyquinoline (33) (125 MHz, DMSO-d ) 43 6 vi