Page 240 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

220

CHAPTER 2
Stereochemistry,
Conformation,
and Stereoselectivity

Fig. 2.30. Active site model of PPL showing the binding of
2-phenylpentane-1,4–diol in an active site. Note the − -
stacking with Phe-216 and placement of the C(4) hydroxyl
near the acyl serine–153 residue. Reproduced from Tetra-
hedron, 55, 14961 (1999), by permission of Elsevier. (See
also color insert.)

group and a phenylalanine residue near the active site. 219 Based on the detailed protein
structure, this model is consistent with the model proposed by Guanti et al. 220 The
model (Figure 2.30) suggests a hydrophilic site and a rather selective hydrophobic
site. The D site is considered to be quite flexible, whereas the B site is particularly
favorable for unsaturated groups.
The enantioselectivity of PPL depends on discrimination in binding of the
substrate. In the case of acylation of simple secondary alcohols, there is poor discrim-
ination for 2-butanol, but 2-hexanol exhibits the maximal E value, and larger alcohols
show good enantioselectivity. 221 (The definition of E is given on p. 140.)

OH O 2 C(CH ) CH 3
2 10
CH (CH ) CO CH CF 3
2 10
2
3
2
R CH 3 PPL R CH 3
R E
C H 2.5
2 5
C H 52
3 7
C H >100
4 9
C 5 H 11 92
C H 90
5 13
Two other lipases of microbiological origin are also used frequently in organic
chemistry. A lipase from Pseudomonas cepacia (formerly identified as Pseudomonas
fluorescens) is often referred to as lipase PS. The binding site for this enzyme is
narrower than those of the other commonly used lipases, and it often has excellent

219
I. Borreguero, J. V. Sinisterra, A. Rumbero, J. A. Hermoso, M. Martinez-Ripoll, and A. R. Alcantara,
Tetrahedron, 55, 14961 (1999).
220 G. Guanti, L. Banfi, and E. Narisano, J. Org. Chem., 57, 1540 (1992).
221
B. Morgan, A. C. Oehschlager, and T. M. Stokes, Tetrahedron, 47, 1611 (1991).