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HO
HO
E
Ferdinand Bohlmann
OH
Scope of the project
Absolute configuration
of secondary OH functions
-X-Ray diffraction
-Synthesis
-Circular dichroism (CD)
-Chiral lanthanide induced shift (LIS)
-Derivatization (=Acylation) & NMR
Mosher’s method
Hoereau’s method
- Applied to polyacetylenes.
shielding
∆δSRL2 = δL2(S) - δL2(R) < 0
and
shielding
∆δSRL1 = δL1(S) - δL1(R) > 0
(R)-MTPA MeO L2
O L1
F3C
O H
Kakisawa model
Experimental details
SAMPLES
7 samples + achiral control (cicudiol) 1
HO
Established model system falcarinol (1)
Conventional structure elucidation OH
2
HO
REACTION
~2 mg/analyte 3
~10 mg (R) or (S)-MTPA-Cl, pyridine, r.t. HO
4
SEPARATION
OH
ACN/H2O (80->98%), HPLC-DAD and
HPLC-SPE-NMR (~20 µg/column) 5
TRAPPING / NMR 6 OH
SPE trapping on GP phase, release in CDCl3 OH
1H NMR for all esters (ns = 128, 500 MHz)
HPLC-DAD (separation)
Agilent 1100
used as usual with regular solvents
SPE (transfer)
Spark; 96 well format
Solid phase extraction allows
analyte selection and solvent
change to NMR solvents
NMR (analysis)
allows all 1D and 2D NMR experiments.
Advantages of the LC-SPE-NMR setup
No analyte isolation needed
No contamination
No loss by adsorption, oxidative breakdown, or salt formation
Solvent change
HPLC in HPLC grade solvent
NMR in deuterated solvent
BUT:
… its easy and straightforward …
BUT:
Tremendous knowledge from offline SPE available
Limitations are well known
HPLC-UV data
HPLC-DAD at 205 nm
Clear separation
Ester / Alcohols
Monitoring of
Reaction progress
Sample degradation
Solvent residues
Derived 1H and 19F NMR spectra
8-(S)-Ester
δS values
8-(R)-Ester
δR values
Application of empirical rules
Kakisawa model
III
R
II
=> (R)
R
Aethusanol A (4)
Results
OH
•LC-SPE-NMR: (R)
4 OH
- no sample workup
1 (R)
(R)
HO
(S) OH
HO
- <20 µg analyte 3
6 OH
(R) (R)
HO
AcO
•Mosher Ester:
7
•Structural data:
- good agreement with literature data / optical rotations
- absolute configuration of rare analytes determined