Synthesis of novel deoxy lambda(5) phospha sugar nucleosides: 1,3-dipolar cycloaddition of an azidophospholane with alkynes.
Several novel phospha sugar nucleosides, analogs of normal sugar nucleosides, were synthesized from a phospholene 1-oxide derivative. Bromination of a phospholene precursor in aqueous organic medium gave regio diastereomers, the threo and erythro bromohydrins 3 (1-bromo-1,3,4-trideoxy-1,4-C-[(R,S)-phenylphosphinylidene]-glycero-tetrofuranose). Further substitution of the threo isomer 3a with sodium azide led to its corresponding azidophospholane 4 (1-azido-1,3,4-trideoxy-2-methyl-1,4-C-[(R)-phenylphosphinylidene]-beta-D-glycero-tetrofuranose). 1,3-Dipolar cycloaddition of 4 with various electron-deficient and electron-rich alkynes afforded triazole derivatives that are nucleoside analogues. The strong electron-withdrawing phosphoryl group in the hemiacetal ring exerted no effect over reaction regioselectivity of the 1,3-dipolar cycloaddition, but steric effects of the alkynes played a vital role on the selectivity, since the regioisomer ratios and the rates and yields of cycloadducts changed as the bulkiness of the substituents on the acetylene changes. Structures of all compounds were unequivocally confirmed by 1H, 13C, and 31P NMR and mass spectral studies. Single crystal X-ray crystallographic analysis of some derivatives allowed determination of configuration of the phospha sugar nucleosides.
Yamashita
M
M
Department of Materials Chemistry, Faculty of Engineering, Shizuoka University, Hamamatsu 432-8561, Japan. tcmyama@ipc.shizuoka.ac.jp
Mallikarjuna Reddy
P
P
Kato
Y
Y
Krishna Reddy
V
V
Suzuki
K
K
Oshikawa
T
T
D000480:Alkynes / Q000737:chemistry; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis*; D009943:Organophosphorus Compounds / Q000737:chemistry*; D014230:Triazoles / Q000737:chemistry*
D000480:Alkynes; D009705:Nucleosides; D009943:Organophosphorus Compounds; D014230:Triazoles; C013194:phospholenes