derivatives (i.e. 8(S),15(S)-diHETE and 5(S),15(S)-diHETE) in a 65 : 35 ratio and in
80 % yield. 5(S),15(S)-diHETE was then purified from its regioisomer by a lacto-
nization procedure, leaving 8(S),15(S)-diHETE unreacted. After purification, suita-
ble protection and hydrolysis, compound 13 was available and further epoxidized by
vanadyl acetoacetonate (Vn acac), leading to a mixture of two isomers in a 5 : 1 ratio
(erythro:threo). The major isomer was then purified over silica, and transformed in
conjugated tetraenoic derivative which upon deprotection afforded lipoxin A 4 (Fig-
ure 19).
16.4.5 Decomposition of PUFA hydroperoxides by metal salts
Various groups have reported the rearrangement of PUFA-HPODs using various
metal salts ina,b-epoxy alcohols. For example, methyl 13(S)-HPODE is trans-
formed by vanadium oxyacetylacetonate (Hamberg, 1987) into methyl 11,12-
epoxy-13-hydroxy octadecadienoate, the two possible diastereoisomers being
formed in equal amounts (Figure 20). The same compounds were obtained with
titanium isopropoxide as catalysts (Piazza et al., 1997), the threo isomer being
slightly predominant. In a later paper, Piazza et al. used nobium ethoxide as catalyst
to obtain access mainly to the erythro isomer (Piazza et al., 1998).
Such transformations are important, sincea,b-epoxy alcohols are natural products
which result from the catabolism of PUFA-HPODs.
16.5 Conclusions
Despite their quite narrow substrate specificity, LOXs are of interest in the field of
organic synthesis because of their generally high regio-, stereo-, and enantioselec-
tivity. This interest lies also in the fact that they catalyze the first step in the hydro-
peroxide catabolic pathway of PUFAs, leading to compounds of major physiological
relevance in both plants and mammals.
From a biotechnological point of view, the use of LOXs is now quite well estab-
lished. One of the most important points for the successful application of such en-
zymes is the need to maintain a sufficient quantity of dissolved oxygen in the reaction
medium during the entire course of lipoxygenation. This is beneficial in terms of
both product yield and product specificity, and also allows the use of high substrate
16.5 Conclusions 355
Figure 20. Action of metal salts upon PUFA-HPODs (Hamberg, 1987; Piazza et al., 1997; 1998).