Enol-acetate nucleosides

Other pyrimidine keto-nucleosides, such as 47a and 47b, could be treated with acetic anhydride-pyridine without glycosylic cleavage.33 The stability of 47a and 47b in this medium permitted elaboration of a new, mild, regioselective synthesis of enol acetates, The reaction of 4 -ketonucleosides of uracil with acetals of N,N-dimethylformamide led,33 after addition of acetic anhydride, to the corresponding enol acetate-nucleosides 77a and 77b. 

Enol acetates of oxonucleosides. These derivatives of oxonucleosides are available by reaction of a nucleoside first with a DMF acetal and then with acetic anhydride. This method is limited to compounds with the 0x0 group in the 4 -position and with a free CO—NH group in the pyrimidine ring. Previous methods of enol... 

A useful method for preparing enol-acetates from uracil 4-keto-nucleosides uses dimethyl formamide diethyl acetal followed by acetic anhydride 2-keto isomers, or N-3-substituted analogues, did not react. Further studies supported a mechanism involving 0-4 esterification of the nucleoside followed by enoliza-tion, which is intramolecularly catalysed by the dimethylamino group, as illustrated in (63). 

Various kinds of chiral acyclic nitrones have been devised, and they have been used extensively in 1,3-dipolar cycloaddition reactions, which are documented in recent reviews.63 Typical chiral acyclic nitrones that have been used in asymmetric cycloadditions are illustrated in Scheme 8.15. Several recent applications of these chiral nitrones to organic synthesis are presented here. For example, the addition of the sodium enolate of methyl acetate to IV-benzyl nitrone derived from D-glyceraldehyde affords the 3-substituted isoxazolin-5-one with a high syn selectivity. Further elaboration leads to the preparation of the isoxazolidine nucleoside analog in enantiomerically pure form (Eq. 8.52).78... 

Subsequent hydration of the enol ether followed by BOM-deprotection and formation of the anomeric acetate provided the nucleosidation precursor 305. In situ silylation of the pyrimidone and activation of the anomeric group with TMSOTf gave the desired 2 -deoxy-3 -0-methyluridine 302 in moderate yield after basic hydrolysis of the tether with no contaminating a-anomer (Scheme 10-98). A similar strategy was used by Sujino and Sugimura to prepare similar compounds [108]. 

The UDP-Gal epimerase system was also one of the early methods to employ pyruvate kinase (PK EC 2.7.1.40) for the conversion of UDP to UTP, with the simultaneous formation of pyruvate from phospho(enol)pyruvate (PEP). Previous kinase systems employed were either more expensive (nucleoside diphosphate kin-ase(EC 2.7.4.6)/ATP) or were thermodynamically less favorable (acetate kinase(EC 2.7.2.1)/acetyl phosphate). Another potentially usefid kinase system has recently been described. Noguchi and Shiba have utilized polyphosphate kinase (PPK) for the formation of UTP from UDP in a UDP-Gal recycling system [13]. Previously, PPK was shown to catalyze the reversible transfer of phosphate from ATP to ADP. Recently, it has been discovered that PPK will also accept other NDP and NTP substrates. For application to recycling systems, poly(phosphate) is more affordable than PEP as a phosphoryl donor. Synthetically, replacement of PK with PPK in the UDPGE-based recycling system efficiently provided LacNAc from GlcNAc on a multi-gram scale. 

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