How recent knowledge on furano-specific enzymes has renewed interest for the synthesis of glycofuranosyl-containing conjugates - Carbohydrate Chemistry: Chemical and Biological Approaches - page 404

group 21 by replacing the standard compound 6 by a more reactive
UMP-N-methylimidazolide. It is interesting to note that UDP-b- L -Araf
was also synthesized by Liu and Zhang 22 and that the tritium labeled
UDP-[6- 3 H]-a- D -Galf was obtained by de Lederkremer and coworkers. 23
In parallel with this standard methodology, Ferri ` res et al. developed a
complementary strategy based on the use of an unprotected thioimidate
as furanosyl donor with either phosphoric acid 24 or UDP in its acidic
form, i.e. a strategy based on a reverse nucleophile vs. electrophile re-
activity. 25 The absence of any protecting groups, on both donor and UDP,
and of any additives resulted in a direct access to various UDP-furanoses
with increased reactivity. Moreover, neither ring expansion nor
UMP-furanoses were observed, and the 1,2-trans anomers could also be
isolated. Interestingly, this strategy was applied to the synthesis of known
natural UDP-furanoses (a- D -Galf, b- L -Araf), postulated D -fucofuranose
(a- D -Fucf), and the non natural 6-fluorinated UDP- D -Galf analogue. 25
An ecient chemo-enzymatic approach was recently proposed by
Field's team. 26 It relied on a tri-enzymatic system using sugar-phosphate
8,UTP,UDP a- D -Glcp in a catalytic amount and the galactose-1-
phosphate uridylyltransferase (Gal-1-PUT). The latter was able to transfer
the uridylyl residue onto the monophosphate. The other two enzymes,
UDP-glucopyrophosphorylase and inorganic pyrophosphorylase, are
required to produce UDP-a- D -Glcp from released a- D -Glcp-1-phosphate,
and hydrolyze the inhibitor pyrophosphate into phosphate, respectively.
This very interesting and ecient strategy was also further applied
by other groups, especially to produce structurally related UDP- D -Galf
analogues 27,28 and methylated derivatives. 29 In addition, Jakeman and
Ferri ` res obtained dTDP-furanoses thanks to mutation of a thymidylyl
transferase. 30,31
To study more precisely the activity of UGM and also find potential
inhibitors, various modulations were introduced, on the original UDP
substrate. Synthetic fluorinated compounds were considered. It is well
known that fluorine atom has physicochemical properties close to that of
a hydroxyl group. Following the above strategies, 6-deoxy-6-fluoro-UDP- D -
Galf was chemically and chemo-enzymatically prepared. 25,28 Earlier,
Blanchard's group synthesized the 2- or 3-fluorinated derivatives of UDP-
a- D -Galp. 13 Many efforts were also focused on potential intermediates
formed during the ring contraction catalyzed by UGM as well as
conformers close to the postulated transition state. Due to the long
debate that occurred in the scientific community about the precise
mechanism of the mutase from M. tuberculosis, it would be hard to
present all synthetic molecular tools that contributed to the elucidation
of this mechanism (Fig. 2).
Nevertheless, the works of Sina¨ and Vincent, 32-44 those of Pinto, 45-50
Kiessling 16,51-58 or Lowary 2,7,59-62 have to be underlined. Amongst these
studies, some of them were dedicated to the elucidation of the tridi-
mensional structure of the enzyme 57,63 and to dynamic interactions
based on STD-NMR techniques. 48,49 Consequently, a range of structures,
including analogues of intermediates or substrates, uridinyl derivatives
missing the furanosyl residue or aromatic compounds, were designed