This dissertation ias been microfilmed exactly as received Mic 60-6419 WHITELEY, Thomas Edward. DEOXY SUGARS; "5—DEOXY—D-GLUCOSE". The Ohio State University, Ph.D., 1960 Chemistry, organic University Microfilms, Inc., Ann Arbor, Michigan DEOXY SUGARS; "£-EEOXY-D-GLUCOSE" DISSERTATION Presented In Partial fulfillm ent of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State U n iv e rs ity by THOMAS EDWARD WHITELEY, B. A ., M. S c . THE OHIO STATE UNIVERSITY I960 Approved by A d v iser Department of Chemistry ACKNOWLEDGMENT The author wishes to express his appreciation to Professor M* L. Wolfram for his guidance and councel in this work, Drs. W, von Bebenburg, F, Shafizadah and A, Thompson have given freely of their time and have provided value advice on manipulative d e t a i l s • Particular thanks are extended to Dr, L. Kuhn of Aberdeen Proving Grounds, Md,, through whose efforts the author received a research assistantship with Professor Wolfrom. Acknowledgment is extended The Ohio State University, the Socony- Mobil Oil Co, and the Department of Health, Education and Welfare, Public Health Service, National Institutes of Health for fellowships and assistantships provided by them. ii TABLE OF CONTENTS INTRODUCTION ...................... ....................................... STATED!! OF THE PROBLEM .................................... HISTORICAL .................................................................. Synthesis of Unsaturated Carbohydrate Derivatives ..................... The G lycals and T heir Rearranged Derivatives ................ The Glycoseens ................................... Synthesis of 2-Hydroxyglycals . The S yn th esis o f V in yl Substituted Sugars ......................... The R eaction o f Diborane irYith O lefin s ................ ...................... The Synthesis of Deo^qjr Sugars . Synthesis by Direct Replacement of Hydroxy, Acyloxy or S u lfon yloxy Groups .......................... Dooxy Sugars by Opening of Epoxide Rings .............................. Deoxysugars From Unsaturated Carbohydrate Derivatives ............ Deoxysugars via Saccharinic Acids ............................ The O p tical P rop erties o f the Furanose Sugars ......................... DISCUSSION OF RESULTS ......................................... The .lercaptolysis of Tetra-O-acetyl-a- L-arablhopyranose ....................... Acetylation of the Uercaptolysis Product .............................. TABLE OF CO'TTETTS (eontd.) Pa^e Deoxysugar Synthesis From IT ............................ U2 Proof of Structure of Ilercaptolysis Product of Tetra-O-ac etyl-a-L- arabinopyranose ............................................... h3 An Explanation For the Synthesis of 5*-S-2thyl-5-thio-L-arabinose Diethyl Idthicacetal by hercaptolysis of Tetra-O-acetyl-a-L-arabinopyranose ................................................... U5 Synthesis of 1,2-0-1sopropylidene- 5 >6-di-O-o-tolylsulfc nyl- a-D-glucose (XI) ........................ $h The Preparation o f l,2-0-lsopropylidene-3 tri-O-D-tolylsu 1fo n y l- a-D-glucose (XI') .............................................................................................. 55 S y n th e sis o f V inyl Substituted Sugars .................................... 56 The Synthesis of 1,2-0- I s opro pyli dene -li-vin yl- a-D-xylo-tetrofuranose(XTII) ................................................... 56 The S7mthesis of 1,2-0- Is opropylidene-3 -C -n -~ tolylsul fo nyl-L-vir.yl- q-fi-xylo-tetrofuranose (XIV) ...................... <8 The Synthesis of 5j6—Dideoxy- 1,2-C-isopropylidene-a-D- . xylo-hexose (XV) .................................................................................................. 59 The S y n th esis o f 5-Deoxy- 1 , 2 - 0 -iscpropylidene-a- D-xvXo-hexcse (XVI) ........................................................... 59 The Preparation of 5-Deoxy- D-threo-hexose Phenylosazone (XVII) ....................................................... 61 The Preparation of 5-Deoxy-D- threo-hexose Phenylosotriazole (XVITI) ................................................ iv TABLE CF C0I:TE:!TS (co-itd.) Pace The P eriod ate O xidation o f g-Peoxy-D-threo-hexose Phenyloso t r la 2ole (XVIII) ............................................................................. 62 The Hydrolyses and Optical Properties of the Synthesized 1 , 2- 0 - 1 sopropylidene-a-D- ighLo-hexoses ..................................................................................... .................. 62 The O ptical P rop erties o f the Synthesised Tcn-pvranose Sugars .................................... 61; Optical Potatory Dispersion of 1 . 2 - 0- 1 sopropylidene-h-vinyl- a.-D-xvlo-tetrofuransoe (XTII), and 1 . 2 - 0 - 1 sopropylidene-3 - 0- £ - tolylsulfonyl-U-vinyl- a-P-xy lo - 1 c tro furanc s e (XIV) ................................. 63 EXPERHIIITAL .......................................................... 7 I* Synthesis and Proof of Structure of 5-S-Sthyl- 5-thio-L-arabinose Diethyl Dithioacetal ........................................................................................ 7 I1 Synthesis of 5-S-"'thyl- 5-thio-L-arabino se Diethyl Dithioacetal ........................... 7 it A. Zinc C hloride C a ta ly st ....................................................................................... 7 I; h . B oron Tri fluori de C a ta ly st ................................................................... 76 Se fL-:idcro Peroxide Combustion Analysis of P-S-Ethyl-£-thio- L-arabinose Diethyl Dithioacetal (VIII) ................................................................................ 76 Preparation of 2,3,ii-Tri-0- ac'. tyl-5-S-ethyl-L-arabinose Diethyl Dithioacetal (II) ................................................................... 79 v ■jabl : op crm a.iTS (contd.) Paye Seni^micro Peroxide Combustion Analysis of 2,3 ,h-Tri-0-acetyl- 5-S-ethyl-£-thio-L-arabinose Diethyl Dithioacetal (!l) ......................................... ........................ 79 The Preparation of 2,3,^-Tri- O-acetyl-^-S-ethyl-5-thio-L- arabinose Dimethylcetal (XXXV) ................................ n A+ter:pted Preparation o f 5-Pec:cy-L-arahinose ................................................. nl The Deductive Pesulfurization o f 5 -Tthyl-5-thio-L-arabinose Diethyl Pittiioacetal . ......................... 33 ^he C-methyl Determination oj' 1 , 5 -Dideoxy-L-arabinitol (D-lyxitcl) (^V) ................................................................................. 8 ? Attempted Preparation cf l , 5-Pid&oxy-2 , 3 ,U -tr i-G - o-nitrobenzcyl-L- arab in i to1 (D-lyxi to 1 ) .............................................................................. f 7 Synthesis and Proof of Structure o f 5 -Decxy-D-xylo-hexo se (" 5 -Deox - EUgHucose'1); Synthesis and Optical Prcoerties of P-Xvlo-hexoses ......................................................................... 87 Tlie Preparation o f 1 ,2 -0 - Iscpropylieene-5 , 6- e i - 0 -o - tclylsulfcnyl-a-D-glucose (XI) ......................................................... :7 The Preparation of l,2,-0- lEcprcpylioerte-3,.5,6-tri-O-o- tolylsulfer.yl-a-D-glucose ................................................................ : 5 The S yn th esis o f 1 ,2 - 0 - I scpropyli dene-4i-vinyT-a- D-xylc-- tetrcJuranose (XITI) ............................................................... 89 The S yn th esis o f 1 ,2 - 0 - Isopropylidene- 3 - 0- £ - “ tolylsulfonyl-k-vlnyl-a- D-xylc-tetrofuranc-se (XIV) .................................................................. 90 vi TABLE OF CC:iTE:TS (contd.) Pa ['e The Synthesis of 5, 6- D id e o x y -l,2-isoprcpylidene- a-P-xylo-hexose (XV) ............................................................................ 90 The Synthesis of 5-Oeoxy- 1 , 2 - 0-isopr opyli dene-a- r-xvTc-hexr se ................................................................... 91 A. Sodiur. Borohycri’e- Alundnuiii Chloride "eduction ......................................... 91 B. Piborane Ee ucticn ............................................................. 92 SIrupy g-H oxy-P-xylc-hcxose .......................................................... 92 g-i-co::y-D-threo-hexose Phenylos^sone (XVH) ......................... 93 5-Be ox -D-threo-hexcse Phenylosotriaz'le ( .nfTT-r j ............. 93 The P riodate Oxidation of the 5-Peoxy-D-thrco-hexose Phenylo.sotrlazole ................... 93 The Acid hydrolysis of the Prepared 1 ,2-0-Is opropyli d.ene Puranose Derivatives ............................................................................ 9h The Optical Potatory Dispersion of 1,2-C- Isop rcpyli cene-U-vinyl-a-D-xylo- tetrofuranose (XIII) and 1,2—O-Isopropylidene- 3 -O-tolylsulfonyl-ij-vi nyl---- D-x y lc - tetrofuranose ............................................................................................ 96 SUiiiAItY ......................................................................................... 98 ChFi .1079........................ CYCAL EIBLIOGFAPEY ................................................................... 101 AU70BIC TAPBT .................... 112 vii LIST OF FIGURES Acid hydrolyses of 1,2-0- isopropylidene-D-xylo- “ hexoses in 2.5 N hydrochloric a c id , 0 .2 2 M in**sugar ....................... Optical rotatory dispersion curves of 1, 2 - 0 -i sopropylidene - U -vinyl-a -P-xyTo-tetrofuran os e in different solvents ....................... Optical rotatory dispersion curve of 1,2-0—iscpropylidene-3-O-p- t o lylsulfonyl-lj -vinyl-«j -P-yylo- tetrofuranose in chloroform