Cchiral amino phosphorus compounds

C-Chiral amino phosphorus compounds, particularly 1-amino- and 2-aminoalkanephosphonic acids, have been a subject of interest for organic chemists due to their interesting biological activity.1cd Among many methods of their stereoselective synthesis, some enzymatic approaches have been reported, which constitute a nice alternative to chemical procedures.

Stereoselective hydrolysis of racemic 1-(N-phenylacetylamino) alkanephos-phonic acids performed in the presence of penicillin acylase under the kinetic resolution conditions gave both the unreacted substrates and the products - the corresponding 1-aminophosphonic acids in high yields and with full enantioselec-tivity. The unreacted N-acyl derivatives were hydrolysed chemically and in this way each enantiomer of the free acid was obtained (Scheme 5).74

A number of 1- and 2-aminophosphonates were resolved by a straight CAL-B-promoted acetylation of the amino group in the substrates rac-58. Surprisingly, ethyl acetate had to be used as an acetylating agent, since the commonly applied vinyl acetate reacted with aminoalkanephosphonates even in the absence of an enzyme (Equation 30, Table 6).75

Scheme 5

R

1-Aminophosphonic acid

Yield (%)

[«]d

Abs. conf.

Me

80

-17.6

(L) (R)

Me

80

+ 17.0

(D) (S)

Ph

73

+24.0

(L) (R)

Ph

71

-23.0

(D) (S)

i-PrCH2

76

-34.5

(L) (R)

PhCH2

77

-50

Kinetic resolution of 1- and 2-aminophosphonates75

Entry R1 R2 n Aminophosphonate 58 Acetylaminophosphonate 59 E

Table 6

Kinetic resolution of 1- and 2-aminophosphonates75

Entry R1 R2 n Aminophosphonate 58 Acetylaminophosphonate 59 E

(%)

[«]d

(%)

[«]d

ee (%)

1

Me

Et

1

40

+6.6

99.5

54

+12

78

64

2

Me

n—Pr

1

41

+ 10.9

100

53

+ 12.5

76

>80

3

Me

i-Pr

1

40

+6.6

100

55

+16.4

72

>70

4

Et

Et

1

44

+7.3

64

42

+23

79

16

5

ch2=ch

Et

1

>90

0

0

0

0

0

0

6

Me

Et

0

41

—8.0

99.7

48

+57.2

90

>100

7

Me

n-Pr

0

42

—1.2

90

42

+56.4

98

>200

8

Me

i-Pr

0

44

—1.5

96

43

+55.3

98

>200

9

Et

Et

0

73

—2.7

18

10

+ 14.4

100

>200

The aminoalkanephosphonic acids which bear an additional hydroxy group in the molecule were usually resolved via enzymatic acylation of this hydroxy group. For example, resolution of N-Cbz-phosphoserine dimethyl ester 60 using various lipases gave poor results. However, lipase PS-promoted acetylation of N-Cbz-phosphoisoserine diethyl ester 61 gave both the unreacted substrate

61 and the O-acetylated product 62 with almost 100% enantiomeric excess (E = 1000).76

Ph"

pr Q

In turn, an attempt at the resolution of phosphothreonine diester using both the acetylation and hydrolysis approaches proved that the reactions were chemo-and diastereoselective, but completely non-enantioselective.77 Another approach to the synthesis of phosphoisoserine was reported by Hammerschmidt et al.78 In the first step, they resolved diisopropyl 2-azido-1-hydroxyethanephosphonate 64

via enzymatic hydrolysis of the acetoxy derivative 63 and then transformed it into the free acid 65 by reduction (Equation 31).78

P(OPri)2

OAc rac-63

P(OPri)2

MeOH/Et3N

H2N""YI OH

Pd/H2

P(OPri)2

(L)-Phosphinotricin 67, which is the active component of naturally occurring antibiotic "biolaphos," was synthesized from the corresponding keto acid 66 via reductive amination catalysed by L-glutamate dehydrogenase (EDH) (Equation 32).79

Each enantiomer of 67 was earlier obtained by an a-chymotrypsin-catalysed resolution of its diethyl ester 68 or its cyclic analogue 69, followed by chemical hydrolysis (Scheme 6).80

Patent literature reports on the analogous resolutions of phosphinotricin using, among others, penicillin G-acylase,81 penicillin G-amidase,81 subtilisin81 or microorganisms such as Enterobacter aerogenes, Klebsiella oxytoca, Corynebac-terium sp., Rhodococcus rubropertinctus and others.82

Was this article helpful?

0 0

Post a comment