Page 367 - Cascade_Biocatalysis_Integrating_Stereoselective_and_Environmentally_Friendly_Reactions

16.2 Iminocyclitol and Aminocyclitol Synthesis 343

F206

Y113′
F131

PGH

′
Figure 16.1 X-ray structure of the active site (Y113 ) denotes a residue from a neigh-
of wild-type FucA in complexation with the boring FucA subunit. The model shows the
′
transition state analog phosphoglycolohy- target residues F131, F206, and F113 which
droxamate (PGH) bound to the active center were independently substituted by alanine.
(PDB: 4FUA) [20]. A prime in the numbering

Among them, the mutant FucA F131A was found to be most active toward the
assayed acceptors including branched substitutions (4d–f, Scheme 16.3) and
the conformationally restrained (R)- and (S)-N-Cbz-prolinal derivatives (7a–d,
Scheme 16.3), which were no substrates for FucA wild type [19]. The other
mutations resulted in lower conversions, whereas no reaction was observed with
Del (207–215). Furthermore, no synergistic effects with the combined mutations
were observed in all cases [19].
The stereochemical outcome of the new FucA F131A was indistinguishable
compared to that obtained for the wild type. However, while the (R)-N-Cbz-
aminoaldehydes yielded the anti(3R,4R)-configured aldol adduct in high diastere-
oselectivity (>2:98 syn(3R,4S)/anti(3R,4R) ratio), the (S) enantiomers depended
on the aldehyde. In the extreme situation, (R)-N-Cbz prolinal derivatives ((R)-7a,b)
gave exclusively the anti(3R,4R) adduct whereas the S counterparts ((S)-7a,c,d)
rendered the syn(3R,4S) one. Protein molecular models were built to gain
insight into the acceptor binding mode that led to this distinct stereochemical
outcome [19].
DHAP-dependent aldolases were also applied in the synthesis of new indolizidine
and quinolizidine iminocyclitols with high configurational diversity [21]. To this
end, we explore the use of (R)and (S)-N-Cbz-piperidin-2-carbaldehyde ((S)-10a and