Abstract
Two novel methods for the preparation of the virtually equimolar mixtures of (S)- and (R)-diastereomers of 5-methoxycarbonylhydroxymethyluridine (mchm5U) have been developed. The first method involved α-hydroxylation of a 5-malonate ester derivative of uridine (5) with SeO2, followed by transformation to (S)- and (R)-5-carboxymethyluridines (cm5U, 8) and, finally, into the corresponding methyl esters. In the second approach, (S)- and (R)-mchm5-uridines were obtained starting from 5-formyluridine derivative (9) by hydrolysis of the imidate salt (11) prepared in the acid catalyzed reaction of 5-cyanohydrin-containing uridine (10b) with methyl alcohol. In both methods, the (S)- and (R) diastereomers of mchm5U were effectively separated by preparative C18 RP HPLC.
Highlights
Two novel methods for the preparation of the virtually equimolar mixtures of (S)- and (R)-diastereomers of 5-methoxycarbonylhydroxymethyluridine have been developed
We present two novel methods for preparation of 1 and 2, where instead of the formation of the uridine C5carbanion, the nal modi cation was introduced by the transformation of nucleoside substrates containing a methyl-derived substituent at C5-uracil position, namely 5-(diethyl malonate-yl) derivative of protected uridine 5 (Scheme 1) or 5-formyluridine derivative 9 (Scheme 2)
We appreciated the accessibility of the “malonate” derivative [5], which was a substrate in synthesis of 5-methoxycarbonylmethyluridine [3]
Summary
Two novel methods for the preparation of the virtually equimolar mixtures of (S)- and (R)-diastereomers of 5-methoxycarbonylhydroxymethyluridine (mchm5U) have been developed. The “malonate” derivative 5 was obtained in a DBU promoted reaction of 20,30,50-O-triacetyl-N3-benzoyl-5-bromouridine [4] and diethyl malonate (ESI, Fig. S1 and S2†).6,15 The C-5,1-oxidation upon treatment with SeO2 was optimized in terms of molar excess (1.5–4 equiv.), temperature (25–100 C), solvent
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callSimilar Papers
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
