Synthesis of a 2,3-dideoxy-2,3-difluorofuranose with the D-lyxo configuration. An intramolecular rearrangement of methyl 5-O-benzoyl-2,3-dideoxy-2,3-difluoro-D-lyxofuranoside observed during the attempted synthesis of 1-(2,3-dideoxy-2,3-difluoro-beta-D-lyxofuranosyl)thymine.
A new sugar, methyl 5-O-benzoyl-2,3-dideoxy-2,3-difluoro-D-lyxofuranoside (8), which features fluorine substituents on adjacent carbon positions above the plane of the tetrahydrofuran ring, was synthesized from 1,2: 5,6-di-O-isopropylidine-alpha-D-allofuranose in seven steps and 22% overall yield. During the synthesis, introduction of the second fluorine atom required conditions more forceful than those normally used with diethylaminosulfur trifluoride (DAST). An attempt to use 8 in the synthesis of the all-cis nucleoside, 1-(2,3-dideoxy-2,3-difluoro-beta-D-lyxofuranosyl)thymine, failed to give the desired product, providing instead 1-(3-deoxy-3-fluoro-2-O-methyl-beta-D-xylofuranosyl)thymine (11), the structure of which was confirmed by an independent synthesis. Formation of the rearranged product occurred with the concurrent loss of fluorine and retention of the methoxy group which was transposed from the anomeric to the 2'-position. The present work highlights the reactive nature of this novel dideoxydifluoro sugar precursor.
Jeong
L S
LS
Laboratory of Medicinal Chemistry, National Cancer Institute, NIH, Bethesda, MD 20892.
Lim
B B
BB
Marquez
V E
VE
D002236:Carbohydrate Conformation; D003837:Deoxy Sugars / Q000737:chemistry*; D006027:Glycosides / Q000737:chemistry*; D015394:Molecular Structure; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
C090305:1-(2,3-dideoxy-2,3-difluorolyxofuranosyl)thymine; C090306:1-(3-deoxy-3-fluoro-2-O-methylxylofuranosyl)thymine; D003837:Deoxy Sugars; D006027:Glycosides; C090304:methyl 5-O-benzoyl-2,3-dideoxy-2,3-difluorolyxofuranoside; D013936:Thymidine