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Basenhydrierte Phosphonsäure‐Derivate von Pyrimidinnucleosiden, Nebenprodukte bei der Desoxygenierung von 2′‐ O ‐Phenoxythiocarbonyl‐Vorstufen
Author(s) -
Morr Michael,
Ernst Ludger
Publication year - 1993
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.1993199301195
Subject(s) - chemistry , hydrolysis , deoxygenation , uracil , cytosine , epimer , medicinal chemistry , stereochemistry , diastereomer , organic chemistry , catalysis , dna , biochemistry
Base‐Hydrogenated Phosphonic Acid Derivatives of Pyrimidine Nucleosides, Side Products in the Deoxygenation of 2′‐ O ‐Phenoxythiocarbonyl Precursors Persilylation of N 4 ‐anisoyl‐1‐(5‐ O ‐benzoyl‐3‐deoxy‐3‐diethoxyphosphorylmethyl‐2‐ O ‐phenoxythiocarbonyl‐β‐ D ‐ribofuranosyl)cytosine ( 1 ) with iodotrimethylsilane followed by a Barton‐McCombie reaction with Bu 3 SnH/azobis(isobutyronitrile) and hydrolysis with Et 3 NH + buffer furnishes, in a side reaction, the N 4 ‐anisoyl‐ O 5′ ‐benzoyl‐3′‐deoxy‐3′‐phosphonomethyl‐3,4,5,6‐tetrahydro‐cytosine lactones 4a and 4b , which are epimers at C‐4 and can be separated by chromatography. Two‐step hydrolysis of 4a and/or 4b yields an epimeric mixture of 1‐(3‐deoxy‐3‐phosphonomethyl‐β‐ D ‐ribofuranosyl)‐3,4,5,6‐tetrahydro‐uracil ( 6a / 6b ). A possible mechanism of the formation of 4a / 4b from 1 via persilylated 2,2′‐anhydro‐ N 4 ‐anisoyl‐(5‐ O ‐benzoyl‐3‐deoxy‐3‐diethoxyphosphoryl‐β‐ D ‐arabinofuranosyl)cytosine ( 9 ) as well as the reactivity of 9 and the behaviour of methyl 5‐ O ‐benzoyl‐3‐deoxy‐3‐diethoxyphosphoryl‐2‐ O ‐phenoxythiocarbonyl‐β‐ D ‐ erythro ‐pentofuranoside ( 17 ) under the same reaction conditions are discussed. The structures of all new compounds are confirmed by their 1 H‐, 13 C‐, 31 P‐NMR and FAB mass spectra.