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Synthesis of [1′,2′,5′,2‐ 13 C 4 ]‐2′‐Deoxy‐ D ‐adenosine by a Chemoenzymatic Strategy to Enable Labelling of Any of the 2 15 Carbon‐13 and Nitrogen‐15 Isotopomers
Author(s) -
Ouwerkerk Niels,
Boom Jacques van,
Lugtenburg Johan,
Raap Jan
Publication year - 2002
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200207)2002:14<2356::aid-ejoc2356>3.0.co;2-s
Subject(s) - chemistry , benzylamine , potassium cyanide , methylamine , organic chemistry , stereochemistry , medicinal chemistry , cyanide
Enzymatic trans ‐ N ‐glycosylation has been selected as the method of choice by which to couple [ 13 C 1 ]‐adenine to [ 13 C 3 ]‐2‐deoxy‐ D ‐ribose. The enzymatic pentosylation of the labelled adenine base was achieved in a two‐step/one‐pot reaction, starting from thymidine labelled in the sugar ring, but not at the thymine base. The efficiency of this thymidine phosphorylase catalysed (TP‐catalysed) and purine nucleoside phosphorylase catalysed (PNP‐catalysed) transamination reaction was demonstrated by a high yield (91%) and stereochemical purity of the obtained [1′,2′,5′,2‐ 13 C 4 ]‐2′‐deoxy‐ D ‐adenosine. To verify that all carbon and nitrogen positions and combination of positions in both the adenine and the sugar could be substituted by 13 C and 15 N at a minimum of cost, each of the steps was optimised to convert the commercially available and isotopically highly enriched (99%) synthons (acetaldehyde, acetic acid, ammonia, benzylamine, formic acid, methylamine, potassium cyanide, potassium thiocyanate and sodium nitrite) as quantitatively as possible. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)