ASYMMETRIC HYDROXYLATION WITH LIPOXYGENASE - THE ROLE OF GROUP HYDROPHOBICITY ON REGIOSELECTIVITY

Changes in the regioselectivity for the lipoxygenase 1 catalyzed oxidation of the unnatural substrates 5a-f [(Z,-Z)-HOOC(CH2)4C( = O)O(CH = CHCH2CH = CHR; R, a-f = n-C5H11-n-C10H21[ to afford regioisomeric diols 3 ](Z,E)-HOCH2CH2CH = CHCH = CHCH(OH)R[ and 4 ](E,Z)-HOCH2CH2CH(OH)CH = CH = CHR] as a function of the hydrophobicity of the distal R group were investigated. The results demonstrate that the ratio of products 3/4 decreases steadily as the hydrophobicity of the distal group is increased incrementally from n-C5H11 to n-C10H21. Conversley, changes in the proximal group hydrophobicity by varying the prosthetic modifier for substrates 6a-e {(Z,Z)-HOOC(CH2)xC-(= O)O(CH2)2CH = CHCH2H = CHC8H17; X, a-e = 2-6) gave opposite changes in the regiospecificity of oxidation. For example, increasing the hydrophobicity of the proximal group from X = 4 = 6 led to an increase in the regioselective formation of diol 3. Decreasing the value of X led to preferential formation of diol 4. Hence, the regiochemical outcome of the enzyme-catalyzed reaction appears to be influenced by the hydrophobic differential between the proximal and distal groups. The data suggests that optimization of the regioselectivity for new substrates can be achieved by careful selection of modifier groups used in the design of substrate structure.