A Route to Carbasugar Analogues - Jonathan Clayden - The ...

Chapter 4 – Synthesis of carbasugars
(270). Numerous research groups have taken advantage of these to access optically
pure cyclitols, one succinct if unselective example by Carless and Malik is shown in
Scheme 4.9. 163
Microbial oxidation of toluene gives optically pure diene 270, which
was protected and dihydroxylated, before the remaining olefin was reduced with good
facial selectivity to give acetonide 271. Hydrolysis gave dehydro α-L-fucose analogue
272 in 14% yield from toluene.
Me
Me
Me
i) Me 2 C(OMe) 2 ,
Pseudomonas putida
OH TFA
ii) OsO 4 , NMO HO
OH
270
OH
Me
Me
H 2 , 20 psi
O AcOH, H 2 O
OH
PtO 2 HO O
100 °C
HO OH
OH
271
70%
6:1
Scheme 4.9 – synthesis of an α-L-fucose analogue by enzymatic dearomatisation 163
OH
272
96%
O
O
66%
2:3
4.1.3 Synthetic outlook
In the recent review by Gomez and Lopez. 156 104 carbapyranose syntheses were
discussed noting the yield, number of steps, type of molecule made and the starting
material; of the 78 optically enriched syntheses only 13 had overall yields above 30%,
interestingly this dropped for the racemic syntheses, of which only one of the 26 had
an overall yield greater than 30%. The yields for the racemic syntheses are
presumably lower for two reasons; most of the racemic syntheses came from less
elaborated starting materials and most research has been focused on enantiomerically
pure sugar analogues.
Since the starting oxazolines can be readily made racemically, a carbasugars synthesis
which used only substrate-controlled selectivity would be equally amenable to racemic
and enantiopure synthesis. Furthermore, the authors of the report took overall yields
from relatively late intermediates such as silane 265 (Scheme 4.8), and it is that a
synthesis of better overall yield can be achieved.
137