01/11/96 * 1

Ergot alkaloids as novel chiral selectors in CE

Benno A. Ingelse, Jetse C. Reijenga,

Henk A. Claessens, Frans M. Everaerts

and Mirko FliegerEindhoven University of Technology, The Netherlands

Academy of Sciences of the Czech Republic

Ergot alkaloidsErgot alkaloids

N

N

H

R2 R1

R3

CH3

R4N

N

H

H N

H

CH3

H

C

O

N

C2H5

C2H5

General formula 1-allyl-terguride

Experimental:Experimental:

P/ACE 2200 Beckman InstrumentsP/ACE 2200 Beckman Instruments Capillary: 50 µm, 300/370 mm, PVA-Capillary: 50 µm, 300/370 mm, PVA-

coatedcoated BGE: BGE: -alanine/acetate + allyl--alanine/acetate + allyl-

terguride, pH 4.0, I=50 mMterguride, pH 4.0, I=50 mM UV-detection, 200 nmUV-detection, 200 nm Samples: 10Samples: 10-4 -4 MM

ExperimentalExperimental setupsetup

BGE and ergot alkaloid

BGE BGE

BGEBGE

BGE BGE

BGEBGE

Typical electropherogram Typical electropherogram using ergot skeletons as using ergot skeletons as

chiral selectorchiral selector

-0.015

-0.01

-0.005

0

0.005

0.01

0.015

0.02

0.025

0 1 2 3 4 5 6

zero

moving boundary

Abs.[AU]

time [minutes]

Influence of pH on the Influence of pH on the resolution of some racemic resolution of some racemic

organic acidsorganic acids

-0.02

-0.015

-0.01

-0.005

0

0.005

0.01

0.015

0.02

0.025

3 3.5 4 4.5 5 5.5 6 6.5 7 7.5

pH 4.0

pH 3.2

MA

HMMPA

VM

TA

MPAMA

HM

VM

Abs.[AU]

time [minutes]

Influence of terguride Influence of terguride concentration on the mobility concentration on the mobility

of the analytesof the analytes

0 5 10 15 20 25

concentration allyl-terguride [mM]

12

14

16

18

20

22

mpa1

mpa2

vm1

vm2

m(eff)

Determination of the KDetermination of the Kcc--value of vanilmandelic acid value of vanilmandelic acid

enantiomersenantiomers

1 1A

cK [C]

MA 5.5 6.3MPA 7.3 8.7HM 7.8 8.9VM 12.0 14.9TA 14.1 14.3

0 5 10 15 20 25

concentration allyl-terguride (mM)

1.00

1.10

1.20

1.30

1.40

K c

µ1/µA

Influence of MeOH on the chiral Influence of MeOH on the chiral separation of the racemic separation of the racemic

organic acidsorganic acids

-0.06

-0.05

-0.04

-0.03

-0.02

-0.01

3 4 5 6 7 8 9

50% MeOH, pH*=5.3

0% MeOH, pH=4.0

MA

MPAHM

TA

MA

MPAHM

VM

TA

Abs.[AU]

time [minutes]

Influence of terguride Influence of terguride concentration on the mobility of concentration on the mobility of

the analytes in 50% MeOHthe analytes in 50% MeOH

0 10 20 30 40 50 60 70

concentration allyl-terguride [mM]

8

10

12

14

16

mpa1

mpa2

vm1

vm2

m(eff)

Determination of the KDetermination of the Kcc-value of -value of --methyl-phenylacetic acid methyl-phenylacetic acid enantiomers using MeOHenantiomers using MeOH

1 1A

cK [C]

MA 11.2 13.2MPA 10.6 13.2HM 12.1 13.2VM 13.5 14.9TA 6.7 7.2

0 5 10 15 20 25

concentration allyl-terguride (mM)

1.00

1.10

1.20

1.30

1.40

K c

µ1/µA

Full separation of some Full separation of some racemic organic acids using 25 racemic organic acids using 25

mg/mL allyl-terguridemg/mL allyl-terguride

-0.002

0.002

0.006

0.01

0.014

0.018

6 8 10

MA

HM

TA

MPA

Abs.[AU]

time [minutes]

Selectivity with and without MeOHSelectivity with and without MeOH

0 20 40 60

Concentration allyl-terguride [mM]

0.00

0.02

0.04

0.06

mandelic acid

50% MeOH 0% MeOH

S

0 20 40 60

Concentration allyl-terguride [mM]

0.00

0.02

0.04

0.06

tropic acid

50% MeOH 0% MeOH

S

ConclusionsConclusions

Allyl-terguride has great potential as a Allyl-terguride has great potential as a chiral selector for organic acidschiral selector for organic acids

The dissociated acid forms stereoselective The dissociated acid forms stereoselective complexes with the ergot alkaloidcomplexes with the ergot alkaloid

Solubility of the ergot-alkaloid in water is Solubility of the ergot-alkaloid in water is limitedlimited

Methanol increases solubility Methanol increases solubility Methanol influences stereoselectivityMethanol influences stereoselectivity