16.4.3 Protection of the hydroperoxide function and obtaining of
chiral synthons
In 1991, Dussaultet al. reported a method of protection of the hydroperoxide func-
tion by acid ketalization with 2-methoxy propene (Dussault et al., 1991) Starting
from enzymatically generated 13(S)-HPODE followed by HPOD protection, they
obtained access to a valuable optically activec-peroxy-a,b-unsaturated aldehyde
(Figure 15) through selective ozonolysis.
This chiral synthon could be further used in olefination through a Wittig reaction.
Indeed, various conjugated dienic hydroperoxides such as 15(S)-HPETE have been
synthesized in this way (Dussault et al., 1991; Dussault and Lee, 1992). In a sub-
sequent paper (Dussault and Lee, 1995) the same team reported, using the same
general methodology, a very elegant synthesis of 5(S)-HPETE. To conduct this
synthesis, synthon 10 was first produced enzymatically, and then used according
to the following retrosynthetic strategy (Figure 16).
Substrate 11 was first chemically synthesized (30 % overall yield, seven steps) in
order to generate 10 through SBLOX-1 oxygenation and subsequent ozonolysis
(Figure 17). Access to 5(S)-HPETE was then completed by Wittig olefination
and deprotection (34 % yield from 11 , six steps).
At the same time, a Japanese group (Baba et al., 1990) used the same perketal
protection strategy to synthesize a structured hydroperoxide phospholipid contain-
16.4 Applications of PUFA hydroperoxides in fine chemistry 353
Figure 15. Protection and ozonolysis of methyl 13(S)-HPODE (Dussault et al., 1991).
Figure 16. Retrosynthetic strategy for the chemo-enzymatic production of 5(S)-HPETE (Dussault and
Lee, 1995).
Figure 17. Chemoenzymatic synthesis of chiral synthon 10 (Dussault and Lee, 1995).