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7‐Halogenated 7‐Deazapurine 2′‐Deoxyribonucleosides Related to 2′‐Deoxyadenosine, 2′‐Deoxyxanthosine, and 2′‐Deoxyisoguanosine: Syntheses and Properties
Author(s) -
Seela Frank,
Xu Kuiying
Publication year - 2008
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200890117
Subject(s) - chemistry , deoxyribonucleosides , substituent , nucleophile , deoxyadenosine , stereochemistry , glycosylation , deoxyribonucleoside , deoxyribonucleotide , medicinal chemistry , organic chemistry , nucleotide , catalysis , biochemistry , enzyme , gene
A series of 7‐fluorinated 7‐deazapurine 2′‐deoxyribonucleosides related to 2′‐deoxyadenosine, 2′‐deoxyxanthosine, and 2′‐deoxyisoguanosine as well as intermediates 4b – 7b, 8, 9b, 10b , and 17b were synthesized. The 7‐fluoro substituent was introduced in 2,6‐dichloro‐7‐deaza‐9 H ‐purine ( 11a ) with Selectfluor ( Scheme 1 ). Apart from 2,6‐dichloro‐7‐fluoro‐7‐deaza‐9 H ‐purine ( 11b ), the 7‐chloro compound 11c was formed as by‐product. The mixture 11b / 11c was used for the glycosylation reaction; the separation of the 7‐fluoro from the 7‐chloro compound was performed on the level of the unprotected nucleosides. Other halogen substituents were introduced with N ‐halogenosuccinimides ( 11a → 11c – 11e ). Nucleobase‐anion glycosylation afforded the nucleoside intermediates 13a – 13e ( Scheme 2 ). The 7‐fluoro‐ and the 7‐chloro‐7‐deaza‐2′‐deoxyxanthosines, 5b and 5c , respectively, were obtained from the corresponding MeO compounds 17b and 17c , or 18 ( Scheme 6 ). The 2′‐deoxyisoguanosine derivative 4b was prepared from 2‐chloro‐7‐fluoro‐7‐deaza‐2′‐deoxyadenosine 6b via a photochemically induced nucleophilic displacement reaction ( Scheme 5 ). The p K a values of the halogenated nucleosides were determined ( Table 3 ). 13 C‐NMR Chemical‐shift dependencies of C(7), C(5), and C(8) were related to the electronegativity of the 7‐halogen substituents ( Fig. 3 ). In aqueous solution, 7‐halogenated 2′‐deoxyribonucleosides show an approximately 70% S population ( Fig. 2 and Table 1 ).