- Phosphodiester cleavage of guanylyl-(3′,3′)-(2′-amino- 2′-deoxyuridine): Rate acceleration by the 2′-amino function
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Hydrolytic reactions of the structural analogue of guanylyl-(3′, 3′)-uridine, guanylyl-(3′,3′)-(2′-amino-2′- deoxyuridine), having one of the 2′-hydroxyl groups replaced with an amino function, have been followed by RP HPLC in the pH range 0-13 at 90°C. The results are compared to those obtained earlier with guanylyl-(3′,3′) -uridine, guanylyl-(3′,3′)-(2′,5′-di-O-methyluridine), and uridylyl-(3′,5′)-uridine. Under basic conditions (pH > 8), the hydroxide ion-catalyzed cleavage of the P-O3′ bond (first-order in [OH-]) yields a mixture of 2′-amino-2′-deoxyuridine and guanosine 2′,3′-cyclic phosphate which is hydrolyzed to guanosine 2′- and 3′-phosphates. Under these conditions, guanylyl-(3′, 3′)-(2′-amino-2′-deoxyuridine) is 10 times less reactive than guanylyl-(3′,3′)-uridine. Under acidic and neutral conditions (pH 3-8), where the pH-rate profile for the cleavage consists of two pH-independent regions (from pH 3 to pH 4 and from 6 to 8), guanylyl-(3′,3′)- (2′-amino-2′-deoxyuridine) is considerably reactive. For example, in the latter pH range, guanylyl-(3′,3′)-(2′-amino-2′- deoxyuridine) is more than 2 orders of magnitude more labile than guanylyl(3′,3′)-(2′,5′-di-O-methyluridine), while in the former pH range the reactivity difference is 1 order of magnitude. Under very acidic conditions (pH +]) compete with the cleavage. The Zn2+-promoted cleavage ([Zn2+] = 5 mmol L-1) is 15 times faster than the uncatalyzed reaction at pH 5.6. The mechanisms of the reactions of guanylyl-(3′,3′)-(2′-amino-2′-deoxyuridine) are discussed, particularly focusing on the possible stabilization of phosphorane intermediate and/or transition state via an intramolecular hydrogen bonding by the 2′-amino group.
- Ora, Mikko,Linjalahti, Heidi,Loennberg, Harri
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p. 1826 - 1832
(2007/10/03)
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- Efficient reduction of azides to amines with tributylstannane. High-yield syntheses of amino and diamino deoxynucleosides
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Treatment of unprotected azido-deoxynucleosides with tributylstannane/AIBN in hot benzene/DMAC (or silyl-protected derivatives in benzene) resulted in formation of the corresponding amino-deoxynucleosides in high isolated yields. A radical process is indicated.
- Samano,Robins
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p. 6293 - 6296
(2007/10/02)
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