carbon 13 (the ‘distal’ region) along with traces of 9-oxygenated product [1404]
(the ‘proximal’ region, Scheme 2.167) [1405].
In addition, it has been shown that soybean lipoxygenase can also be used for the
oxidation of nonnatural 1,4-dienes, as long as the substrate is carefully designed to
effectively mimic a fatty acid [1406], insufficient reaction rates can be improved by
an increased the oxygen pressure (up to 50 bar) [1407]. The (Z,Z)-1,4-diene moiety
of several long-chain alcohols could be oxidized by attachment of a prosthetic
group (PG), consisting of a polar (CH 2 ) n –CO 2 H or a CH 2 –O–(CH 2 ) 2 –OH unit,
which serves as a surrogate of the carboxylate moiety (Scheme 2.167) [1408]. Oxidation occurred with high regioselectivity at the ‘normal’ (distal) site and the
optical purity of the peroxides was >97%. After chemical reduction of the hydroperoxide (e.g., by Ph 3 P [1409]) and removal of the prosthetic group, the
corresponding secondary alcohols were obtained with retention of
configuration [1410].
In addition, the regioselectivity of the oxidation could be inverted from ‘normal’
(distal) to ‘abnormal’ (proximal) by changing the length of the distal substituent R
and the spacer arm linking the prosthetic group PG (Table 2.4 and Scheme 2.167).
Enhancing the lipophilicity of R from n-C 5 to n-C 10 led to an increased reaction at
the ‘abnormal’ site to form predominantly the proximal oxidation product. In
contrast, extension of the spacer arm caused a switch to the ‘distal’ product.
OOH
n-C 5 H 11
(CH 2 ) 6 -CO 2 H
n-C 5 H 11
(CH 2 ) 6 -CO 2 H
lipoxygenase
soybean
e.e. 95%
linoleic acid
12
9
O 2
S
PG
O
O
R
PG
HOO
O
O
R
PG
OOH
O
O
R
lipoxygenase
soybean
distal
proximal
PG = prosthetic group
proximal
distal
lipoxygenase
soybean
S
S
O 2
O 2
PG
R
distal/proximal e.e. [%] distal
(CH 2 ) 4 CO 2 H
n-C 5 H 11
95:5
98
(CH 2 ) 4 CO 2 H
CH 2 Ph
89:11
98
(CH 2 ) 4 CO 2 H
(CH 2 ) 3 C(O)CH 3
99:1
97
CH 2 O(CH 2 ) 2 OH n-C 5 H 11
99:1
98
CH 2 O(CH 2 ) 2 OH n-C 8 H 17
10:90
96
CH 2 O(CH 2 ) 2 OH homogeranyl a
1:99
96
a = (CH 2 ) 2 CH=CCH 3 (CH 2 ) 2 CH=C(CH 3 ) 2 .
Scheme 2.167 Natural and non-natural substrates of soybean lipoxygenase
2.3 Oxidation Reactions
195
(the ‘proximal’ region, Scheme 2.167) [1405].
In addition, it has been shown that soybean lipoxygenase can also be used for the
oxidation of nonnatural 1,4-dienes, as long as the substrate is carefully designed to
effectively mimic a fatty acid [1406], insufficient reaction rates can be improved by
an increased the oxygen pressure (up to 50 bar) [1407]. The (Z,Z)-1,4-diene moiety
of several long-chain alcohols could be oxidized by attachment of a prosthetic
group (PG), consisting of a polar (CH 2 ) n –CO 2 H or a CH 2 –O–(CH 2 ) 2 –OH unit,
which serves as a surrogate of the carboxylate moiety (Scheme 2.167) [1408]. Oxidation occurred with high regioselectivity at the ‘normal’ (distal) site and the
optical purity of the peroxides was >97%. After chemical reduction of the hydroperoxide (e.g., by Ph 3 P [1409]) and removal of the prosthetic group, the
corresponding secondary alcohols were obtained with retention of
configuration [1410].
In addition, the regioselectivity of the oxidation could be inverted from ‘normal’
(distal) to ‘abnormal’ (proximal) by changing the length of the distal substituent R
and the spacer arm linking the prosthetic group PG (Table 2.4 and Scheme 2.167).
Enhancing the lipophilicity of R from n-C 5 to n-C 10 led to an increased reaction at
the ‘abnormal’ site to form predominantly the proximal oxidation product. In
contrast, extension of the spacer arm caused a switch to the ‘distal’ product.
OOH
n-C 5 H 11
(CH 2 ) 6 -CO 2 H
n-C 5 H 11
(CH 2 ) 6 -CO 2 H
lipoxygenase
soybean
e.e. 95%
linoleic acid
12
9
O 2
S
PG
O
O
R
PG
HOO
O
O
R
PG
OOH
O
O
R
lipoxygenase
soybean
distal
proximal
PG = prosthetic group
proximal
distal
lipoxygenase
soybean
S
S
O 2
O 2
PG
R
distal/proximal e.e. [%] distal
(CH 2 ) 4 CO 2 H
n-C 5 H 11
95:5
98
(CH 2 ) 4 CO 2 H
CH 2 Ph
89:11
98
(CH 2 ) 4 CO 2 H
(CH 2 ) 3 C(O)CH 3
99:1
97
CH 2 O(CH 2 ) 2 OH n-C 5 H 11
99:1
98
CH 2 O(CH 2 ) 2 OH n-C 8 H 17
10:90
96
CH 2 O(CH 2 ) 2 OH homogeranyl a
1:99
96
a = (CH 2 ) 2 CH=CCH 3 (CH 2 ) 2 CH=C(CH 3 ) 2 .
Scheme 2.167 Natural and non-natural substrates of soybean lipoxygenase
2.3 Oxidation Reactions
195