Synthesis of 2,3 -dideoxy-3 ,3 -gem-dic-alkyl pyranonucleoside analogues
Other Title(s)
تحضير مماثلات النيوكليوسيدات من نوع بايرانو-2،3-ثنائي ديوكسي-3، 3-التوأم-ثنائي-C-الكيل
Dissertant
al-Mumin, Thana Mahdi Abd al-Karim
Thesis advisor
al-Araji, Suad Mustafa
al-Fattahi, Yusuf Ali
University
University of Baghdad
Faculty
College of Science
Department
Chemistry Department
University Country
Iraq
Degree
Ph.D.
Degree Date
2007
English Abstract
Branched-chain sugar nucleosides are present in a wide range of both naturally occurring and synthetic products, some having biological activites such as antitumor, antiviral or antibacterial.
The key step in the total synthesis of these nuclosides is the stereocontrolled formation of a new C-C bond at the branching point.
The present work is the synthesis of new 2/, 3/-dideoxy-3/, 3/-gem-di-Calkyl pyrano nucleoside analogues.
The designed multisteps synthetic route to these nucleosides start with 4,6-O-benzylidene glucoside (106), prepared in one step from methyl-α- D-glucopyranoside (105), then p-toluenesultfonylation in pyridine afforded 2, 3-trans-ditosyl (107) which was selectively suitable to prepare allo-epoxy sugar (108) via intramolecular nucleophilic displacement, since it was readily opened by hydride anion using sodium borohydride gave the desired 2-deoxy sugar (109), oxidation of (109)with DMSOAc2O afforded the 3-keto sugar derivative (110).
Nucleophilic addition of three different compounds containing active methylene groups, nitromethane, 1,3-propanedinitrile (malononitrile) and 2,4-pentanedione (acetylacetone), to the keto sugar (110) using phase transfer conditions (PTC) gave, 3-C-nitromethyl (111) and 3-C-dicyanomethyl (147), sugar derivatives, while acetylacetone gave 3,3-di-C-diacetyl methyl (139) in one step.
Dehydration of (111) and (147) with DMSO-Ac2O afforded the, 3-C-nitromethylene (112) and 3-C-dicyanomethylene (148), derivatives respectively.
These derivatives are the key synthetic intermediates as Micheal acceptor.
Treatment of (112) with nitromethane, malononitrile and acetylacetone using PTC afforded different types of 2, 3-deoxy-3, 3-gem-di-C-alkyl carbohydrate derivatives 3, 3-di-C-dinitromethyl (113), 3-C-dicyanomethyl-3-C-nitromethyl (123) and 3-C-diacetylmethyl-3-Cxviii nitromethyl (131) respectively, similarly (148) gave, after treatment with malononitrile and acetylaceton; 3,3-di-C-dicyanomethyl (149) and 3-Cdiacetylmethyl- 3-C-dicyanomethyl (157) respectively, while the other gem-di-C-alkyl carbohydrate (139) was synthesized in previous step.
To prepare the nucleosides target, the branched chain sugars converted to their active form (1-bromosugar derivatives).
This convertion comprised the hydrolysis of 4, 6-O-benzylidene group of the prepared sugar derivatives to the corresponding diol (114), (124), (132), (150), (158) and (140) respectively, acetylation with acetic anhydride/acetic acid with low percents of sulfuric acid furnished the acetylated sugar (115) (125), (133), (151), (159) and (141) respectively, bromination with HBr in glacial acetic acid, forming 1-bromo sugars (116), (126), (134), (152) (160) and (142) respectively, which were subjected to condensation with theophylline mercury salt (117) to give acetylated nucleosides (119) (127), (135), (153), (161) and (143) respectively.
Deblocking of these nucleosides with sodium methoxide in methanol afforded our target the free nucleoside analogues type of (2/,3/-dideoxy-3/,3/- gem-di-C-alkylpyrono) theophylline, (120), (128), (136), (154), (162) and (144) respectively.
In a similar manner indole mercury salt (118) were condensed with 1-bromo sugar derivatives mentioned above to give acetylated nucleoside analogues (121), (129), (137), (155), (163) and (145) respectively, which upon hydrolysis afforded the target free nucleoside analogues as (2/,3/- dideoxy-3/,3/-gem-di-C-alkyl-pyrano)indole (122), (130), (130), (138), (156), (164) and (146)respectively.
The prepared compounds were identified by elemental analysis, specific rotation ([α]D) measurements and by spectroscopic methods: FT-IR, UV, 1H-NMR and 13C-NMR.
Main Subjects
No. of Pages
193
Table of Contents
Table of contents.
Abstract.
Abstract in Arabic.
Chapter One : Introduction.
Chapter Two : Experimental.
Chapter Three : Results and discussion.
References.
American Psychological Association (APA)
al-Mumin, Thana Mahdi Abd al-Karim. (2007). Synthesis of 2,3 -dideoxy-3 ,3 -gem-dic-alkyl pyranonucleoside analogues. (Doctoral dissertations Theses and Dissertations Master). University of Baghdad, Iraq
https://search.emarefa.net/detail/BIM-600277
Modern Language Association (MLA)
al-Mumin, Thana Mahdi Abd al-Karim. Synthesis of 2,3 -dideoxy-3 ,3 -gem-dic-alkyl pyranonucleoside analogues. (Doctoral dissertations Theses and Dissertations Master). University of Baghdad. (2007).
https://search.emarefa.net/detail/BIM-600277
American Medical Association (AMA)
al-Mumin, Thana Mahdi Abd al-Karim. (2007). Synthesis of 2,3 -dideoxy-3 ,3 -gem-dic-alkyl pyranonucleoside analogues. (Doctoral dissertations Theses and Dissertations Master). University of Baghdad, Iraq
https://search.emarefa.net/detail/BIM-600277
Language
English
Data Type
Arab Theses
Record ID
BIM-600277