Schiral sulfanamides

Subtilisin E was found to efficiently catalyse enantioselective hydrolysis of certain N-acyl arenesulfinamides 34 to arenesulfinamides 35. Noteworthy, among the potential substrates only those having the chloroacetyl, bromoacetyl and dihy-drocinnamoyl groups were recognized and hydrolysed by the enzyme in a highly stereoselective manner. Some other N-acyl derivatives gave inferior results and the N-acetyl and N-butanoyl analogues proved totally unreactive (Equation 18, Table 2).46 The molecular modelling that was made for the first time for this kind of compound suggested that N-haloacetyl and N-dihydrocinnamoyl groups mimic the phenylalanine moiety and thus bind the sufinamide to the enzyme active site. The enantioselectivity is believed to stem from a favourable hydrophobic interaction between the aryl group of the fast-reacting (R)-enantiomer of the arenesulfinamide and the S1 leaving group pocket in subtilisin E.46

However, when subtilisin E was replaced by subtilisin Carlsberg, the hydrolysis of the S-N bond in some N-acyl arenesulfinamides 34 unexpectedly became the main hydrolytic process giving under the kinetic resolution conditions, in addition to the unreacted substrates, the corresponding sulfinic acids and

Table 2

Enzymatic hydrolysis of N-acyl arenesulfinamides46

Table 2

Enzymatic hydrolysis of N-acyl arenesulfinamides46

Entry

Ar

R

Conversion (%)

ee of (S)-34

ee of (R)-35

Ea

1

Ph

CH2Cl

14

16

97

>150

2

Ph

(CH2)2Ph

14

16

99

>150

3

p-Tol

CH2Cl

36

56

97

>150

4

p-Tol

CH2Br

36

99

89

>150

5

p-Tol

(CH2)2Ph

47

89

99

>150

6

p-ClC6H4

CH2Cl

35

52

97

>150

7

p-ClC6H4

(CH2)2Ph

9

10

99

>150

8

p-MeOC6H4

CH2Cl

21

25

94

>150

9

p-MeOC6H4

(CH2)2Ph

40

65

98

>150

10

p-Tol

CH2OMe

28

33

84

26

11

p-Tol

(CH2)2Pri

13

14

91

24

12

p-Tol

Me

0

0

0

0

13

p-Tol

(CH2)3

0

0

0

0

a The substrates also underwent 1-3% spontaneous chemical hydrolysis; the E values shown were corrected for this hydrolysis.

a The substrates also underwent 1-3% spontaneous chemical hydrolysis; the E values shown were corrected for this hydrolysis.

carboxamides (Equation 19).47 Several experiments were carried out to prove that in this case also the enzyme active site was involved.48 The crucial proof was obtained on the basis of the electrospray mass spectroscopy, which clearly indicated the formation of an O-sulfinyl enzyme (sulfinylated most probably on the active site serine).49 Thus, this reaction constitutes an example of the catalytic promiscuity of enzymes, which was demonstrated by the fact that the enzyme favoured the unnatural functional group in the presence of the normal functional group.

Was this article helpful?

0 0

Post a comment