The mono-nitrite (or formate) esters of vic-diols obtained via enzymatic ringopening of epoxides in presence of nitrite (or formate) are unstable and undergo
spontaneous (nonenzymatic) hydrolysis to furnish the corresponding diols. This
protocol offers a useful complement to the asymmetric hydrolysis of epoxides.
Depending on the type of substrate and the enzymes used, enantio-complementary
epoxide hydrolysis can be achieved [2058].
A one-pot two-step transformation of ethyl (S)-4-chloro-3-hydroxybutanoate
(obtained via asymmetric bioreduction of the corresponding β-ketoester) via
(reversible) epoxide-formation followed by ring-opening with cyanide was accomplished on a kg-scale using a halohydrin dehalogenase mutant. Ethyl (R)-4-cyano4-butanoate was thus obtained in a highly chemoselective fashion without formation of byproducts, which plagued the chemical process. The latter product is a key
intermediate for the synthesis of antihypocholesterolemic ‘statin’ agents [2059]
(Scheme 2.236).
References
References to Sect. 2.1
1. Bornscheuer UT, Kazlauskas RJ (2006) Hydrolases in Organic Synthesis, 2nd ed. WileyVCH, Weinheim
2. Boland W, Fr€ oßl C, Lorenz M (1991) Synthesis 1049
3. Lee HC, Ko YH, Baek SB, Kim DH (1998) Bioorg. Med. Chem. Lett. 8: 3379
Hal
OH
R
O
R
H
O
O
OH
R
O
-
H
O
OH
OH
R
O-N=O
OH
R
C≡N
OH
R
N 3
OH
R
OH
CO 2 Et
Cl
O
CO 2 Et
OH
CO 2 Et
N≡C
Buffer
Halohydrin
Dehalogenase Halide (Cl
-
, Br
- or I
- )
Buffer /
spont.
hydrolysis
Halohydrin
Dehalogenase
Buffer
Buffer /
Halohydrin
Dehalogenase
Buffer / N 3
-
Halohydrin
Dehalogenase
Halohydrin
Dehalogenase
Halohydrin
Dehalogenase
(S)*
(R)*
* Switch in CIP-sequence priority
C≡N -
-HCl
C≡N
-
NO 2
-
rac
*
*
*
*
Scheme 2.236 Regio- and enantioselective ring-opening of epoxides using nonnatural nucleophiles catalysed by halohydrin dehalogenase
References
261