This dissertation has been microfilmed exactly as received 66—10,005 CHAKRAVARTY, Prasenjit, 1935- I. SYNTHESIS OF DERIVATIVES OF 2,6-DIAMINO- 2,6-DIDEOXY-D-MANNOSE AND 2-AMINO-3,6- ANHYDRO-2-DEOXY-D-MANNOSE. II. AMINO DERIVATIVES OF STARCHES. ATTEMPTED SYN­ THESIS OF 2-AMINO-3,6-ANHYDRO-2-DEOXY- AMYLOSE AND DEGRADATIVE EXPERIMENTS ON N-ACETYL AMINATED AMYLOSE. University Microfilms, Inc., Ann Arbor, Michigan This dissertation has been microfilmed exactly as received 66—10,005 CHAKRAVARTY, Prasenjlt, 1935- The Ohio State University, Ph.D., 1966 Chemistry, organic University Microfilms, Inc., Ann Arbor, Michigan I . SYNTHESIS OF DERIVATIVES OF 2,6-DIAMIN0-2,6-DIDE0X'£. D-MAMOSE AND 2-AMIN0-3»6-ANHYDR0-2-DE0XY^-MANN0SE I I . AMINO DERIVATIVES OF STARCHES. ATTEMPTED SYNTHESIS OF 2-AMIN0-3*6-ANHYDR0-2-DE0XYAMYL0SE AND DEGRADATIVE EXPERIMENTS ON N-ACETYL AMINATED AMYLOSE DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio. S ta te U n iv ersity Hy Prasenjit Chakravarty» B.Sc.*, M.Sc. **** The Ohio State University 1966 Approved by Adviser Department of Ghemistiy ACKNOWLEDGMENTS The author wishes to express his sincere appreciation to. Professor M. L. Wolfrora for his interest and suggestions throughout this investigation» The author would like to thank Dr. D. Horton for his helpful discussions and suggestions and also would like to thank Dr. M. I. Taha for his invaluable help in experimentation. The research assistantship from the Northern Utilization Re­ search and Development Division of the United States Department of Agriculture* Peoria* Illinois (from October 1* I 96I* to June 4, 1965» on The Ohio State University Research Foundation Project I 30I and from October 6, 1965* to present on The Ohio State University Research Foundation Project 2130), is gratefully acknowledged. The research assistantship from the Department of Health* Education* and Welfare* United States Public Health Service* National Institutes of Health* Bethesda* Maryland (from June 5» I 965» to October 5» 1965» on The Ohio State University Research Foundation Project 759H* is also gratefuliy acknowledged* i.i VITA November 14» 1935 ............................. # Bom - Chinsura, India 1 9 5 1 .......................... .........................................Hooghly Collegiate School» Chinsura,, India 1 9 5 6 .............................................................. B*Sc. Honours In Chemistry University of Calcutta» India 1958 * ........................................................ M.Sc. in Organic Chemistry University of Calcutta, India 195 9 ......................... » Research Assistant, Indian Council of Medical Research, Calcutta, India 1960 - I 96I .........................................................Lecturer in Chemistry, Gurudas College, Calcutta, India 1961 - I 966 .......................... Research Assistant, Department of Chem istry, The Ohio S ta te University, Columbus, Ohio After graduation ..... .................. Research Associate, Department of Pathology, New York University Medical C enter, New York, N. Y. i i i CONTENTS Page Acknowledgments 11 V i t a ............................................................................ I l l Introduction . ....................................................................................... 1 Development of the Problem ................................................................. 9 Dlamlno Sugars .......................................................................................... 27 Importance Syntheses Statement of the Problem ..................................................................... 48 G raphical Summary - PART I» .................................. ♦ 49 Discussion of Results - PART I ............................... ...... 51 PART I I . , ................................................ 65 Experimental - PART I. ................................................ 69 Preparation of 2-acetamido-2-deo%y-o-D-glucose .... 69 Preparation of 2-acetamido-2-deoxy-D-mannose .... » 70 Preparation of 2-acetamido-l^3»4,6-tetra- O-acetyl-2-deoxy-g-D-mannose * ..................... 71 Acetic anhydride-sodlum acetate method Acetic anhydride-pyridine method Phenyl 2-acetamldo-3*4 »6-tr1-0-acetyl-2- deoxy-o-D-mannoslde ...... ...................... ... 72 Ey using zinc chloride as catalyst By using g-toluenesulfonic acid as catalyst Phenyl 2-acetamldo-2-deoxy-a-D-mannopyranoslde .... 73 Phenyl 2-acetamldo-2-deo35y-6-0-(£-tolylsulfonyl)« o-D-mannopyranoslde ............................................... 74 Iv CONTENTS (Contd.) Page Phenyl 2-acetamido-3 >^-di-^-acetyl-2-deoxy- 6-0-(£-tolylsulfonyl)-o-D-inannoside . ....................... 75 Phenyl 2-acetamido-3 *4-di-^-acetyl-6-azldo-2,6- dideoxy-a-D-mannoside ............................................................. 75 From phenyl 2-acetamido-3a/+-di-0-acetyl-2- deoxy-6-0- (^-tolylsulfonyl)-a-D-mannoside From phenyl 2-ac etamido-2-deoxy-6-0- (g-tolyl- snlfonyl)-o-D-mannopyranoslde Phenyl 2»6-diacetamido-3»4-di-^-acetyl-2» 6-dideoxy- o-D-mannoside . ................................................................ 77 From phenyl 2-acetamido-3 i^-di-O-acetyl-6- azido-2 »6-dideaxy-a-D-mannoside From phenyl 2-acetam ido-6-azido-2»6-dideoxy- ouD-mannopyranosid e 2>6-Diamino-2»6~dideaxy-p-D-mannose dihydrochloride . 78 From phenyl 2*6-diacetamido-3>^-di-û-acetyl- 2,6-dideoxy-a-D-mannoside From phenyl 2-acetamido-6-azido-2>6-dideoxy- cw-D-mannopyranoslde From phenyl 2-acetamldo-3,4-di-0-acetyl-6- azldo-2 »6-dideoxy-a-DHmannoside Phenyl 2-acetamido-3 »6-anhydro-2-deoxy-o-D- mannopyranoside ..................................................................... .... 80 Sodium hydroxide method Sodium acetate method Phenyl 2-acetamido-^-0-acetyl-3 »6-anhydro-2- deoxy-o-D-mannoside . ...................................................* 81 2-Araino-3 »6-anhydro-2-deoxy-D-mannofuranos e hydrochloride ................................................................................. 82 2-Acetamido-l,5-di-0-acetyl-3»6-anhydro-2- deoxy-D-mannose . ......................................................................... 83: V CONTENTS (Contd.) Page 2-Àcetamido-3,6-anhydro-2-deoxy-D-mannose diethyl dithioacetal ............... 83 2-Acetamido-^ >.5-di-0-acetyl-3 >6-anhydro-2- deoxy-D-mannose diethyl dithioacetal ...... 8^ Attempted opening of 3>6-anhydro ring in phenyl 2-acetamido-3 %6-anhydro-2-deo%y-a-D-manno-_ pyranoside with boron trichloride .............................. 84 Experimental - PART II. .............................. .... 86 Preparation of pyridine-swollen am ylose ....... 86 Preparation of 6-0-(£-tolylsulfonyl)ainylose .... 8? Preparation of 3 »6-anhydroanylose .......... 87. 3$6-Anhydro-2-0-C£-tolylsulfonyl)amylose...... 88 From 3»6-anhydroamylose at elevated temperature From 2,6-bis-0-(p-tolylsulfoiQrl)amylose From 3 »6-anhydroamylose a t room tem perature 3>6-Anhydro-2-0-(methylsulfpnyl)amylose ...... 89 Reaction of 3*6-anhydro-2-0-(^-tolylsulfonyl) amylose with hydrazine ..................... 89 Reaction of 3»6-anhydro-2-0-(2-tolylsulfonyl) amylose with sodium a aide * ................................... ............ 90 Reaction of 3»6-anhydro-2-0-(£-tolylsulfonyl) amylose: w ith sodamide .................................. 90 Reaction of 3»6-an]r^ro-2-0-(methylsulfonyl) anylose with hydrazine ....................................................... 90 Hydrolysis of N-acetyl aminated amylose ..................... 91 Mercaptolysis of N-acetyl aminated amylose ...... 91 Summaiy - PART I . ........................................................... 93 PART I I . .............................. 96 Chronological Bibliography ......................... 98 v i INTRODUCTION Amino sugars or glycosamines are carijohydrates containing amino groups in place of alcoholic hydroxyl groups, and differ from glycosyl- amines (N-glycosides), in which the amino group takes the place of a hemiacetal hydroxyl. A characteristic difference between amino sugars and glueosylamines is generally the stability of the carbon-nitrogen bond in the former.and the lability of this bond in the latter (1,2)# (1) W* W. Pigman, "The Gaibohydrates," 2d ed., Academic Press, Inc., New York, N. Y., p. 4o6 (1957)« (2) F. Micheel, "Chemie der Zucker and Polysaccharide," 2d ed., Akademische Verlagsgesellschaft, Leipzig, p. l64 (19^6). Confounds genetically related to the amino sugars are their reduction products alditols containing amino groups — the amino sugar alditols. Amino sugar alditols having an amino group on a priiom ary carbon atom are usually called glycamines. Finally, compounds similar to the amino sugars and amino sugar alditols are the amino derivatives of cyclitols, the polyhydrojqrcyclohexanes, or the inos- amines (3,4). (3) S. J. Angyal and L. Anderson, Advan. Carbohydrate Chem., 14, 183 (1959). (4) T. Postemak, "The Cyclitols," Holden-Day, Inc., San Francisco, Calif, p. 203 (1965). 2 For a long time only two amino sugars — both of natural origin — were known: 2-amino-2-deoxy-D-glucose (5) and 2-amino-2-deoxy-D- (5) G. Ledderhose» Ber.» Bg, 1200 (18?6)* galactose (6)» irtiose configuration was established (7) in 1937-1939 (6) P. A. Levene and F. B, LaForge, J . B io l. Chem.» 18» 123 (1914). "■ (7) W. N. Haworth» W. H, G. Lake» and S. Peat» J. Chem. Soc.» 271 (1939). and (8) in 1943. Individual, synthetic amino sugars and amino sugar (8) S. P. James » F. Smith» M. Stacey» and L. F. Miggins » Nature» 1^6» 308 (1945). alditols- were prepared by Fischer and co-workers