Multicomponent diversity and enzymatic enantioselectivity as a route towards both enantiomers of α-amino acids-a model study

Article abstract of DOI:10.1016/j.tetasy.2006.09.014

A model study on a new, enantioconvergent method for the synthesis of chiral, nonracemic α-amino acids is presented. α-Acetoxyamides obtained in a Passerini multicomponent reaction are selectively hydrolyzed by Wheat Germ lipase. Studies on conversion of the thus obtained, enantiomerically enriched α-hydroxyamides into α-aminoamides are presented. Products of these reactions are then hydrolyzed to give α-amino acids.

Full text of DOI:10.1016/j.tetasy.2006.09.014

Tetrahedron: Asymmetry 17 (2006) 2667–2671
Multicomponent diversity and enzymatic enantioselectivity as a
route towards both enantiomers of a-amino acids—a model study
Wiktor Szymanskib and Ryszard Ostaszewskia,*
aInstitute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
bFaculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland
Received 23 August 2006; accepted 11 September 2006
Abstract—A model study on a new, enantioconvergent method for the synthesis of chiral, nonracemic a-amino acids is presented. a-
Acetoxyamides obtained in a Passerini multicomponent reaction are selectively hydrolyzed by Wheat Germ lipase. Studies on conversion
of the thus obtained, enantiomerically enriched a-hydroxyamides into a-aminoamides are presented. Products of these reactions are then
hydrolyzed to give a-amino acids.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
Our general synthetic concept is presented in Figure 1. In
order to fulfill the first of the above mentioned require-
ments, we have decided to employ the Passerini multicom-
ponent reaction as a first step, leading to substrate D for
enzymatic hydrolysis. This enables us to use the easily
accessible aldehydes A as starting materials. It also allows
convenient introduction of diverse R0 and R00 moieties
(from isocyanide B and carboxylic acid C), which deter-
mine the enantioselectivity of enzymatic hydrolysis and
success of further transformations. A large number of pos-
sible structures for B and C allows the adjustment of the
synthetic method to the synthesis of various a-amino acids
F. In case of a need for a single enantiomer of the product,
a simple protocol for the transformation of alcohols E into
esters D with inversion of the configuration inversion is
also established.
Synthesis of enantiomerically enriched a-amino acids has
drawn interest since the beginning of asymmetric synthesis,
resulting in the development of many widely used proto-
cols.1 Today the stereocontrolled synthesis of these com-
pounds is also a matter of crucial importance, due to
their wide applicability in medicine,2 asymmetric catalysis3
and bioanalysis.4
Enzymatic asymmetric catalysis is also widely used for the
preparation of a-amino acids.5 Such syntheses are usually
easier and cheaper than their chemical analogues6 and
more readily fulfill the requirements of green chemistry.7
The goal of this study was to establish a new chemo-
enzymatic method for the preparation of enantiomerically
enriched a-amino acids. Such a method should possess
certain features, which include: a possibility of convenient
introduction of diverse modifications (in order to adjust
the synthetic method towards the synthesis of various
structures); easy accessibility of the substrate and finally
high enantioselectivity of the enzymatic step. Other fea-
tures include a high yield and a low amount of racemisa-
tion in synthetic transformations. Generation of both
enantiomers of desired product, which is a key feature in
bioactivity screening studies, is also necessary.
NH2
R'
OH
HO
HN
R
R
A
B
RCHO
R'
OCOR''
R
O
O
O
+
+
R'NC
E
F
HN
+
NH2
R'
OCOR''
R
O
C R''COOH
HO
rac-D
HN
R
O
D
ent-F
*
Corresponding author. Tel.: +48 22 343 2120; fax: +48 22 632 66 81;
e-mail: rysza@icho.edu.pl
Figure 1. General synthetic concept.
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.09.014

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W. Szymanski, R. Ostaszewski / Tetrahedron: Asymmetry 17 (2006) 2667–2671
Table 1. Enzymatic hydrolysis optimization study
2. Results and discussion
No
1
Co-solventa
Time
30 d
Product
Yield/%
eeb/%
E
Phenylalanine was chosen as a target compound for the
model study (Scheme 1). Our first goal was to examine
the possibility of enantioselective, enzymatic hydrolysis of
the racemic precursor of the target compound.
c-Hex
(S)-5
(R)-4
22
74
28.0
3.0
2
2
3
4
i-Pr2O
TBME
Et2O
48 h
30 h
48 h
(S)-5
(R)-4
33
40
54.4
58.7
6
35
55
Compound rac-4 was obtained in a Passerini reaction
between phenylacetic aldehyde 1, p-methoxybenzyl iso-
cyanide 2 and acetic acid 3. Initially, a group of lipases
was tested. The group consisted of Wheat Germ lipase,
Novozym 435A, Porcine Pancrease lipase, Candida rugosa
lipase, Amano AK Lipase, Rhizopus niveus lipase, Candida
lypholytica lipase, Pseudomonas cepacia lipase and Pig Li-
ver esterase. Of the enzymes tested, only Wheat Germ lipase
performed the hydrolysis. Our previous study has shown
that the stereochemical outcome of these reactions depends
strongly on the co-solvent used. The results of the optimi-
zation study are shown in Table 1.
(S)-5
(R)-4
42
44
87.8
76.5
(S)-5
(R)-4
33
49
92.7
69.8
aAbbreviations used: TBME—tert-butyl-methyl-ether, c-Hex—cyclo-
hexane.
b Determined by HPLC with Daicel Chiracel OD-H column.
tioconvergent way both from (R)-4 by basic hydrolysis
(99% yield) and from (S)-5 by an effective (93% overall
yield) sequence of simple synthetic steps. Inversion of con-
figuration was obtained in an SN2 reaction of p-toluene-
sulfonyl ester of alcohol 5 with caesium acetate. Other
sulphonyl esters (i.e., mesylate and triflate) were also inves-
tigated, but gave poorer yields or led to racemisation of the
product.
The enzyme has shown the highest enantioselectivity (55, as
counted from the conversion-independent equation) when
ethyl ether (Table 1, entry 4) was used as a co-solvent.
Finally, this method was used in our model study.
The same enantioconvergent procedure (Scheme 1) leads to
In order to assign the configuration of the products of
enzymatic hydrolysis, compounds (S)-4 and (S)-5 were syn-
thesized from commercially available, enantiomerically
pure phenylalanine, using procedures well described in
synthetic literature.8,9
the preparation of (S)-5 in a satisfying yield.
To complete the model study of a-amino acid preparation,
it was necessary to establish a convenient method of trans-
formation of alcohol (S)-5 into target compound [(R)-8,
Scheme 2]. In the model study, compound (S)-5 was trans-
formed into methanesulfonic acid ester (R)-7. SN2 reaction
of this ester with sodium azide in the presence of DABCO,
DMAP and crown ether afforded an azide, which was con-
veniently reduced with hydrogen and a palladium catalyst
to give compound (R)-8. The yield of these steps was
almost quantitative (96% over three steps).
It should be emphasized that enzymatic kinetic resolution
yields both enantiomers of desired product in yields lower
than 50%. This is advantageous, when both enantiomers
are required, but in case of demand for a single enantiomer,
a method for more effective synthesis had to be established.
This goal was achieved by a transformation of one of the
products of enzymatic hydrolysis into another (Scheme 1,
syntheses c and d). Namely, (R)-5 was prepared in an enan-
Acidic hydrolysis of (R)-8 afforded a-amino acid (R)-9.
Conventional methods of purification (crystallization,
O
O
OH
O
1
HN
c
Ph
(S)-5
(S)-4
O
Ph
99%
+
O
NH
NC
a
b
33%, 93% e.e
+
d
95%
d
95%
OAc
O
2
c
OAc
(R)-5
O
rac-4
83 %
99%
HN
(R)-4
+
CH3COOH 3
O
Ph
48%, 70% e.e
Scheme 1. Synthesis of alcohol 5. Reagents and conditions: (a) DCM, 20 ꢁC, 48 h; (b) lipase from Wheat Germ, phosphate buffer 7.0/Et2O (8:2), 20 ꢁC,
48 h; (c) NaOH, methanol/water, ultrasound; (d) (1) TosCl, Et3N, DCM, 20 min; (2) CsOAc, crown ether, DMF, 66 h.

W. Szymanski, R. Ostaszewski / Tetrahedron: Asymmetry 17 (2006) 2667–2671
2669
O
O
a
b,c
d,e,f
71%
(S)-5
O
MsO
NH
H2N
NH
97%
99%
OH
H2N
Enantiomeric purity 98 %
O
O
(S)-7
(R)-9
(R)-8
Scheme 2. Synthesis of amino acid 9. Reagents and conditions: (a) MsCl, Et3N, DMAP, DCM, 20 ꢁC, 30 min; (b) NaN3, DABCO, DMAP, benzo-15-
crown-5, 40 ꢁC, 24 h; (c) H2, Pd/C, methanol, 4 h; (d) 6 M HCl, reflux, 20 h; (e) CbzCl, 4 N NaOH, 1 N NaHCO3; (f) H2, Pd/C, methanol.
ion-exchange chromatography) did not yield analytically
pure compounds, therefore, the purification of material
obtained was performed by in situ introduction of benzyl-
oxycarbonyl (Cbz) moiety, extraction of the protected
compound and reductive cleavage of the protecting group.
The enantiomeric purity of thus obtained target compound
was 98%.
After 90 h the solvent was evaporated and the product
was purified by flash chromatography (silica gel, hexane–
ethyl acetate, 4:1 v/v). Yield: 89%. Mp 79–81 ꢁC (ethyl ace-
tate/hexane); Rf = 0.68 (ethyl acetate/hexane; 4:6; v/v).
Anal. C19H21NO4 requires: C, 69.71; H, 6.47; N, 4.28.
1
Found: C, 69.75; H, 6.49; N, 4.28; H NMR (400 MHz,
CDCl3): d 2.05 (s, 3H, CH3CO), 3.21 (m, 2H, CH2NH),
3.79 (s, 3H, CH3O), 4.33 (m, 2H, CH2CHO), 5.41 (t, 1H,
J = 6 Hz, CHC(O)), 6.10 (s, 1H, NH), 6.80–7.26 (m, 9H,
2ArH); 13C NMR (100 MHz, CDCl3): d 20.93, 37.59,
42.60, 55.23, 74.34. 113.98, 126.89, 128.37, 129.02,
129.56, 129.64, 135.74, 159.00, 168.64, 169.36; Retention
time of enantiomers: TR = 11.993 min, TS = 13.573 min.
3. Conclusion
A model study on a new, chemoenzymatic procedure for
the preparation of both enantiomers of uncoded a-amino
acids is presented. Starting aldehyde (Fig. 1, A) was trans-
formed into a-acetoxyamide (rac-D), which was hydro-
lyzed by Wheat Germ lipase into enantiomerically
enriched alcohol (E). An enantioconvergent approach en-
ables a synthesis of both enantiomers of alcohol E in a high
yield. A method for the transformation of alcohol (E) into
target a-amino acid (F) was also established. Depending on
the synthetic path chosen, preparation of either F or ent-F
is possible.
4.2. Enzymatic hydrolysis of rac-4
Ester rac-4 (50 mg) was dissolved in 10 ml of solvent
(water/co-solvent, 8:2, v/v). Lipase from wheat germ
(E.C. 3.1.1.3, 3 mg) was added in one portion to the sus-
pension and stirred in a shaker at 300 rpm at room temper-
ature for the amount of time given in Table 1. Extraction
with ethyl acetate, concentration in vacuo and purification
of the resulting residue by flash chromatography (silica gel,
hexane–ethyl acetate) afforded ester (R)-4 and alcohol (S)-
5. Analysis for the products of hydrolysis in water/ethyl
ether (Table 1, entry 4): Ester (R)-4: yield 48%. EeR
(HPLC): 70%. Other analysis consistent with rac-4. Alco-
hol (S)-5: yield 33%. EeS (HPLC): 93%; mp 78–80 ꢁC (ethyl
acetate/hexane); Rf = 0.43 (ethyl acetate/hexane; 4:6; v/v).
Anal. C17H19NO3 requires: C, 71.56; H, 6.71; N, 4.91.
4. Experimental
Optical rotations were measured with a JASCO DIP-360
polarimeter. NMR spectra were measured with Varian
200 GEMINI and Varian 400 GEMINI spectrometer.
TLCs were performed with silica gel 60 (230–400 mesh,
Merck) and silica gel 60 PF254 (Merck), respectively.
HPLC experiments were carried out on DAICEL CHIRA-
CEL OD-H column with a pre-column, eluent: hexane/iso-
propanol 9:1 (v/v), flow: 1 ml/min. CHN analysis was per-
formed on Perkin–Elmer 240 Elemental Analyzer and
CHNS analysis on Heraeus Vario EL III apparatus.
1
Found: C, 71.62; H, 6.76; N, 4.87. H NMR (200 MHz,
CDCl3): d 2.60 (br s, 1H, OH), 2.90 (dd, 1H, J = 13.9,
8.2 Hz, CH2CHO), 3.23 (dd, 1H, J = 13.9, 4.1 Hz,
CH2CHO), 3.72 (s, 2H, CH3), 4.32 (m, 3H, ArCH2N,
CHOH), 6.77 (s, 1H, NH), 6.80–7.31 (m, 9H, 2ArH); 13C
NMR (50 MHz, CDCl3): d 41.00, 42.72, 55.43, 72.97,
114.14, 127.08, 128.82, 129.23, 129.69, 130.00, 136.90,
159.10, 172.50. Retention time of enantiomers: TR =
9.745 min, TS = 10.625 min.
4.1. Acetic acid rac-1-(4-methoxy-benzylcarbamoyl)-2-phen-
yl-ethyl ester rac-4
To a solution of acetic acid (2 mmol, 172 ll) in DCM
(1 ml) were added phenylacetic aldehyde (2.2 mmol,
225 ll) and (p-methoxy)benzylisocyanide (2.14 mmol,
315 mg, solution in 1 ml of DCM) in room temperature.
4.3. Chemical hydrolysis of (R)-4
Ester (R)-4 (50 mg, 0.15 mmol) was dissolved in 3 ml of
methanol. Aqueous NaOH solution (4 M, 0.10 ml) was

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W. Szymanski, R. Ostaszewski / Tetrahedron: Asymmetry 17 (2006) 2667–2671
added and the mixture was sonicated for 30 min. The
solvent was evaporated, the residue was brought up in
HCl (1 M, 5 ml) and washed with ethyl acetate (3 · 5 ml).
Combined organic layers were dried (MgSO4), and the
solvent was evaporated, to yield product (42.5 mg, 99%).
Rf = 0.43 (ethyl acetate/hexane; 4:6; v/v). Anal.
C17H19NO3 requires: C, 71.56; H, 6.71; N, 4.91. Found: C,
see the procedure above) was dissolved in DCM (6 ml). Tri-
ethylamine (1.12 ml, 8.00 mmol) and methanesulfonyl
chloride (232 ll, 3.00 mmol) were added in one portion.
The mixture was stirred for 30 min, the solvent was evapo-
rated and the product was purified by flash chromatogra-
phy (silica gel, hexane–ethyl acetate, 4:6, v/v). Yield:
99%. Rf = 0.60 (hexane–ethyl acetate; 4:6; v/v); mp 119–
25
1
71.62; H, 6.76; N, 4.87; H NMR (200 MHz, CDCl3): d
120 ꢁC (ethyl acetate/hexane); ½aꢀD ¼ ꢁ66:1 (c 1.0, chloro-
2.60 (br s, 1H, OH), 2.90 (dd, 1H, J = 13.9, 8.2 Hz,
CH2CHO), 3.23 (dd, 1H, J = 13.9, 4.1 Hz, CH2CHO),
3.72 (s, 2H, CH3), 4.32 (m, 3H, ArCH2N, CHOH), 6.77 (s,
1H, NH), 6.80–7.31 (m, 9H, 2ArH); 13C NMR (50 MHz,
CDCl3): d 41.00, 42.72, 55.43, 72.97, 114.14, 127.08,
128.82, 129.23, 129.69, 130.00, 136.90, 159.10, 172.50.
form). Anal. C18H21NO5S requires: C, 59.49; H, 5.82; N,
3.58. Found: 59.48; H, 5.86; N, 3.88; 1H NMR
(200 MHz, CDCl3): d 2.53 (s, 3H, CH3SO2), 3.12 (dd,
1H, J = 14.4, 9.1 Hz, CH2CHO), 3.53 (dd, 1H, J = 14.4,
3.6 Hz, CH2CHO), 3.86 (s, 3H, CH3O), 4.42–4.50 (m,
2H, ArCH2N), 5.22 (dd, 1H, J = 9.1, 3.6 Hz, CHC(O)),
6.67 (s, 1H, NH), 6.89–7.43 (m, 9H, 2ArH); 13C NMR
(50 MHz, CDCl3): d 37.89, 38.71, 43.07, 55.42, 81.66.
114.21, 127.60, 128.89, 129.08, 129.87, 135.64, 167.56.
4.4. Chemical hydrolysis of rac-4
The above described conditions yielded rac-4. Retention
times of enantiomers: TR = 9.745 min, TS = 10.625 min.
4.7. (R)-2-Amino-N-(4-methoxy-benzyl)-3-phenyl-propion-
amide (R)-8
4.5. Acetic acid (S)-1-(4-methoxy-benzylcarbamoyl)-2-phen-
yl-ethyl ester (R)-4
To a solution of methanesulfonic acid (S)-1-(4-methoxy-
benzylcarbamoyl)-2-phenyl-ethyl ester (S)-7 (200 mg,
0.55 mmol) in DCM (3 ml) were added 1,4-diaza-bicy-
clo[2.2.2]octane (102 mg, 0.90 mmol), 4-dimehylaminopyri-
dine (10 mg), sodium azide (1 mmol) and benzo-15-crown-
5 (10 mg). After 20 h the desired azide was purified by flash
chromatography (silica gel, hexane–ethyl acetate, 4:1, v/v).
To a stirred solution of (S)-2-hydroxy-N-(4-methoxy-
benzyl)-3-phenyl-propionamide (S)-5 (400 mg, 1.40 mmol,
25
>99% ee, ½aꢀD ¼ ꢁ71:1 (c 1.0, chloroform) as obtained in
the correlation study; for general procedure see Refs. 8
and 9) in DCM (8 ml) were added triethylamine (580 ll,
4.20 mmol) and p-toluenesulfonyl chloride (400 mg,
2.10 mmol). After 18 min, the solvent was evaporated
and the product was purified by flash chromatography (sil-
ica gel, hexane–ethyl acetate, 8:2) to give 590 mg (96%) of
Yield: 98%. Rf = 0.83 (hexane–ethyl acetate; 4:6; v/v)
25
½aꢀD ¼ ꢁ21:8 (c 1.0; chloroform). Anal. C17H18N4O2 re-
quires: 65.79; H, 5.85; N, 18.05. Found C, 65.60; H, 6.08;
1
N, 17.95; H NMR (400 MHz, CDCl3): d 3.06 (dd, 1H,
toluene-4-sulfonic
acid
(S)-1-(4-methoxy-benzylcarb-
J = 8.0, 14.4 Hz, PhCH2), 3.35 (dd, 1H, J = 4.4, 14.4 Hz,
PhCH2), 3.86 (s, 3H, CH3O), 4.22 (dd, 1H, J = 4.4,
8.0 Hz, CHN3), 4.30–4.37 (m, 2H, PhCH2NH), 6.48 (br s,
1H, NH), 6.82–7.29 (m, 9H, 2ArH); 13C NMR
(100 MHz, CDCl3): d 38.44, 42.93, 55.24, 65.43, 114.02,
127.15, 128.61, 129.90, 129.41, 129.50, 136.00, 159.04,
168.19. A sample of this compound (0.37 mmol, 115 mg)
was dissolved in methanol (8 ml). To this mixture 10%
Pd/C (10 mg) was added and hydrogen was fluxed through
the solution (from a rubber balloon through a needle) for a
period of 2 h. The reaction mixture was then filtered
through a bed of Celite and the solvent was evaporated,
to give white crystals (104 mg, 99%). Mp 84–85 ꢁC; 1H
NMR (400 MHz, CDCl3): d 1.54 (s, 2H, NH2), 2.73 (dd,
1H, J = 9.2, 13.6 Hz, PhCH2CH), 3.25 (dd, 1H, J = 4.0,
13.6 Hz, PhCH2CH), 3.63 (dd, 1H, J = 4.0, 8.8 Hz,
CHNH2), 3.77 (s, 3H, CH3O), 4.30–4.40 (m, 2H,
PhCH2NH), 6.82–7.31 (m, 9H, 2ArH), 7.56 (s, 1H, NH);
13C NMR (100 MHz, CDCl3): d 40.82, 42.43, 55.11,
56.27, 113.82, 126.63, 128.54, 128.83, 128.92, 129.19,
130.30, 137.68, 158.73, 173.77.
amoyl)-2-phenyl-ethyl ester. Yield: 96%; mp 96 ꢁC (ethyl
acetate/hexane); Rf = 0.71 (hexane–ethyl acetate; 4:6;
25
v/v); ½aꢀD ¼ ꢁ50:4 (c 1.0, chloroform). Anal. C24H25NO5S
requires: C, 65.58; H, 5.73; N, 3.19. Found: C, 65.79; H,
5.76; N, 3.11; 1H NMR (400 MHz, CDCl3): d 2.42 (s,
3H, ArCH3), 3.05 (dd, 1H, J = 14.4, 7.2 Hz, CH2CHO),
3.17 (dd, 1H, J = 14.4, 4.0 Hz, CH2CHO), 3.80 (s, 3H,
CH3O), 4.25–4.33 (m, 2H, ArCH2N), 5.02 (dd, 1H,
J = 7.2, 4.0 Hz, CHC(O)), 6.43 (s, 1H, NH), 6.80–7.53
(m, 13H, 3ArH); 13C NMR (100 MHz, CDCl3): d 21.63,
38.36, 42.74, 55.24, 80.62, 113.96, 126.86, 127.73, 128.34,
128.91, 129.17, 129.71, 129.89, 132.14, 134.63, 145.22,
158.98, 167.46. A sample of this compound (100 mg,
0.227 mmol) was dissolved in DMF (2 ml). Caesium ace-
tate (88 mg, 0.45 mmol) and benzo-17-crown-5 (10 mg)
were added in one portion. The mixture was stirred for
66 h in 50 ꢁC, and then poured into water (20 ml). This
mixture was extracted with ethyl acetate (3 · 15 ml). The
collected organic phases were dried (MgSO4) and the sol-
vent was evaporated. The product was purified by flash
chromatography (silica gel, hexane–ethyl acetate 1:1) to
give 73.5 mg (99%). EeR (HPLC): >99%. Other analyses
were consistent with rac-4.
4.8. (R)-Phenylalanine (R)-9
(R)-2-Amino-N-(4-methoxy-benzyl)-3-phenylpropionamide
(R)-8 (180 mg, 0.63 mmol) was refluxed in 6 M HCl (10 ml)
for 20 h. The solvent was then removed and the residue was
dissolved in 4 N NaOH (6 ml) and 1 M NaHCO3 (1.5 ml)
and benzyl chloroformate (0.50 mmol, 72 ll). After 20 h,
another portion of benzyl chloroformate was added
4.6. Methanesulfonic acid (S)-1-(4-methoxy-benzylcarb-
amoyl)-2-phenyl-ethyl ester (S)-7
(S)-2-Hydroxy-N-(4-methoxy-benzyl)-3-phenyl-propion-
amide (S)-5 (571 mg, 2.00 mmol, from correlation study,

W. Szymanski, R. Ostaszewski / Tetrahedron: Asymmetry 17 (2006) 2667–2671
2671
2. (a) Clausen, R. P.; Bra¨uner-Osborne, H.; Greenwood, J. R.;
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(0.50 mmol, 72 ll). After 43 h, the reaction mixture was
washed with ethyl ether (2 · 25 ml). Collected organic
phases were washed with 1 M NaOH (2 · 20 ml). Collected
aqueous fractions were slowly poured into a stirred mixture
of 4 M HCl (50 ml) and ethyl acetate (80 ml). Aqueous
phase was washed with ethyl acetate (2 · 20 ml). Collected
organic phases were dried (MgSO4) and the solvent was
evaporated. The residue was dissolved in methanol
(10 ml). To this mixture 10% Pd/C (10 mg) was added
and hydrogen was fluxed through the solution for 2 h.
Then the reaction mixture was filtered through a bed of
Celite and the solvent was evaporated, to give white crys-
25
tals (74 mg, 71%). ½aꢀD ¼ ꢁ7:3 (c 1.0, acetic acid, lit.:10
ꢁ7.5, enantiomeric purity: 98%); ESI MS(ꢁ): 164.1
(MꢁH+)ꢁ, 100%.
Acknowledgement
This work was supported by Polish State Committee for
Scientific Research, Grant K071/P04/2003.
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