Chiral auxiliary 1,2-O-cyclopentylidene-5-deoxy-5-isopropylamino-alpha- D-xylofuranose 51 and its enantiomer 52 were synthesized from D-xylose and L-xylose respectively and treated with PC13 to form cyclic phosphochloridites 58 and 67, and then reacted with 5'-O- t-butyldimethylsilylthymidine to give diastereornerically pure cyclic phosphoramidites 60 and 68. They were coupled with 3'-O-t-butyldimethylsilylthymidine in the presence of 2-bromo-4,5-dicyanoimidazole 46 as catalyst, and then sulfurized with Beaucage's reagent to form protected dithymidine phosphorothioates 62 and 72 stereoselectively. After deprotection, Sp and Rp dithymidine phosphorothioates 65 and 66 were obtained respectively in 98% diastereomeric excess. The mechanism of the coupling reaction which involves only one inversion in the transformation of the phosphoramidites (60, 68) to the dithymidine phosphorothioates (65, 66) is discussed. The effect of the acidity of the catalyst on the stereoselectivity and the rate of the coupling reaction was studied. / The synthesis and separation of diastereomers of protected dithymidine boranophosphates Sp-107 and Rp-108 gave the dimers Sp-109 and Rp-110 in a stereospecific manner. These dimers will be incorporated into oligonucleotides to synthesize mixed backbone oligonucleotides. To confirm the stereochemistry of the dimers Sp-109 and Rp-110, the free dithymidine boranophosphates Sp- 115 and Rp-116 were synthesized, the configurations at the phosphorus atom of which were assigned by comparison with spectral data from the literature. / A stereoselective synthesis of a dinucleotide boranophosphate Sp- 115 with a de of >98%, using (S)-3-hydroxyl-4-(2-indolyl)butyronitrile 28-(S) as chiral auxiliary, is described. The conversion of phosphite triester to boranophosphate by BH3-Me2S-proceeds with retention of configuration at the phosphorus atom. The procedure may be adaptable to the solid phase synthesis.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.34980 |
| Date | January 1998 |
| Creators | Jin, Yi, 1963- |
| Contributors | Just, George (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Chemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001643029, proquestno: NQ44466, Theses scanned by UMI/ProQuest. |
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