Absolute Configurational Assignment of Acyclic Hydroxy Carboxylic Acids: A New Strategy in Exciton-Coupled Circular Dichroism

Article abstract of DOI:10.1021/jo971589w

A new strategy in exciton-coupled circular dichroism (ECCD) is described for the configurational assignment of α-hydroxy carboxylic acids.Using 9-anthryldiazomethane (4), carboxyl groups can be selectively derivatized with a chromophore suitable for exciton coupling.In combination with the 2-naphthoate chromophore linked to the α-hydroxy group, the absolute stereochemistry of α-hydroxy carboxylic acids can be easily deduced from a single CD measurement.The usefulness of the new method is demonstrated with a series of α-hydroxy acids with different side chains.The developed microscale method is also useful for chiral amino acids and natural products containing carboxylic groups or similar strucutral units.

Full text of DOI:10.1021/jo971589w

3
22
J . Org. Chem. 1998, 63, 322-325
Absolu te Con figu r a tion a l Assign m en t of Acyclic Hyd r oxy
Ca r boxylic Acid s: A New Str a tegy in Exciton -Cou p led Cir cu la r
Dich r oism †
Katja H o¨ r, Olaf Gimple, Peter Schreier, and Hans-Ulrich Humpf*
Universit a¨ t W u¨ rzburg, Lehrstuhl f u¨ r Lebensmittelchemie, Am Hubland, D-97074 W u¨ rzburg, Germany
Received August 26, 1997X
A new strategy in exciton-coupled circular dichroism (ECCD) is described for the configurational
assignment of R-hydroxy carboxylic acids. Using 9-anthryldiazomethane (4), carboxyl groups can
be selectively derivatized with a chromophore suitable for exciton coupling. In combination with
the 2-naphthoate chromophore linked to the R-hydroxy group, the absolute stereochemistry of
R-hydroxy carboxylic acids can be easily deduced from a single CD measurement. The usefulness
of the new method is demonstrated with a series of R-hydroxy acids with different side chains.
The developed microscale method is also useful for chiral amino acids and natural products
containing carboxyl groups or similar structural units.
The exciton-coupled circular dichroic (ECCD) method
order to avoid interactions with preexisting chromophores,2
(ii) chromophores with intense absorptions resulting in
strong interactions over a large distance, e.g., porphyrins
is a nonempirical microscale procedure for determining
the absolute configuration and conformation of organic
molecules containing two or more chromophores and has
been widely used in the field of natural products.1 To
introduce the chromophore, hydroxyl groups are con-
verted into various para-substituted benzoate groups,
which may or may not be identical. When two identical
benzoate groups interact through space, they give rise
to a bisignate CD curve, the signs of which are defined
nonempirically by the absolute twist between the electric
transition moments of the coupling chromophores, i.e.,
if the first Cotton effect (CE) at longer wavelength is
positive, then the twist is clockwise, and vice versa.
ECCD can be extended to nondegenerate systems con-
sisting of two different chromophores. For example, the
bichromophoric 9-anthroate/p-methoxycinnamate deriva-
tives of 1,2-polyols result in characteristic CD spectra for
each stereochemical pattern.10
3
with ꢀ ) 350 000, and (iii) chromophores which are
useful for induced chirality.4 The methods developed so
far are most commonly applied to compounds bearing two
or more hydroxyl or amino groups that may easily be
derivatized with an exciton-coupling chromophore. Re-
cently we have developed a novel approach for the
assignment of the absolute configuration of R- and
â-hydroxy carboxylic acids using 9-anthryldiazomethane
(4) as a new chromophoric reagent.5 In this paper we
describe the application of the new method to a variety
of R-hydroxy carboxylic acids with different side chains
in order to check the influence of conformational effects
on the resulting CD curves. Moreover, on the basis of
computer calculations and NMR experiments, the pre-
ferred conformation of the chromophoric derivatives is
presented.
Recent studies have focused on extending the ap-
plicability of ECCD to unexplored areas by developing
Chiral R-hydroxy acids are important building blocks
6
a
6b
for the synthesis of optically active glycols, halo esters,
6
c
6d
7
(i) chromophores with red-shifted absorption maxima in
epoxides, and amino acids. Several enzymatic and
8
chemical methods have been employed for the synthesis
†
of R-hydroxy functionalized carboxylic acids. Further-
more, R-hydroxy acids and related structural units are
widespread in bioactive natural products, i.e., the anti-
Dedicated to Waldemar Adam on the occasion of his 60th birthday.
Corresponding author. Phone: +49 931 8885483. Fax: +49 931
*
8
885484. E-mail: humpf@pzlc.uni-wuerzburg.de.
X
Abstract published in Advance ACS Abstracts, December 1, 1997.
9
cancer drug Taxol or antibiotics such as amphotericin B.
(1) (a) Harada, N.; Nakanishi, K. Circular Dichroic Spectroscopys
Exciton Coupling in Organic Stereochemistry; University Science
Books: Mill Valley, CA, 1983. (b) Nakanishi, K.; Berova, N. In Circular
Dichroism Principles and Applications; Nakanishi, K., Berova, N.,
Woody, R. W., Eds; VCH Publishers Inc.: New York, 1994.
(7) (a) Wong, C.-H; Matos, J . R. J . Org. Chem. 1985, 50, 1992-1994.
(b) Nakamura, K.; Inoue, K.; Ushio, K.; Oka, S.; Ohno, A. J . Org. Chem.
1988, 53, 2589-2593. (c) Effenberger, F. Angew. Chem. 1994, 106,
1609-1619. (d) Adam, W.; Fell, R. T.; Hoch, U.; Saha-M o¨ ller, C. R.;
Schreier, P. Tetrahedron: Asymmetry 1995, 6, 1047-1050. (e) Adam,
W.; Lazarus, M.; Saha-M o¨ ller, C. R.; Schreier, P. Tetrahedron: Asym-
metry 1996, 8, 2287-2292.
(8) (a) Evans, D. A.; Morrissey, M. M.; Dorow, R. I. J . Am. Chem.
Soc. 1985, 107, 4346-4348. (b) Brown, H. C.; Chandrasekharan, J .;
Ramachandran, P. V. J . Org. Chem. 1986, 51, 3394-3396. (c) Corey,
E. J .; Link, J . O. Tetrahedron Lett. 1992, 33, 3431-3434. (d) Mikami,
K.; Terada, M.; Nakai, J . J . Am. Chem. Soc. 1990, 112, 3949-3954.
(9) (a) Nicolau, K. C.; Guy, R. K. Angew. Chem., Int. Ed. Engl. 1995,
34, 2079-2090. (b) Omura, S.; Tanaka, H. In Macrolide Antibiotics:
Chemistry, Biology and Practice; Omura, S., Ed.; Academic Press: New
York, 1984; 351-404.
(2) (a) Cai, G.; Bozhkova, N.; Odingo, J .; Berova, N.; Nakanishi, K.
J . Am. Chem. Soc. 1993, 115, 7192-7198. (b) Gargiulo, D.; Ikemoto,
N.; Odingo, J .; Bozhkova, N.; Iwashita, T.; Berova, N.; Nakanishi, K.
J . Am. Chem. Soc. 1994, 116, 3760-3767.
(3) Matile, S.; Berova, N.; Nakanishi, N.; Novkova, S.; Philipova,
I.; Blagoev, B. J . Am. Chem. Soc. 1995, 117, 7021-7022.
(4) (a) Person, R. V.; Monde, K.; Humpf, H.-U.; Berova, N.; Nakan-
ishi, K. Chirality 1995, 7, 128-135. (b) Schreder, B.; Lukacs, Z.;
Schmitt, M.; Schreier, P.; Humpf, H.-U. Tetrahedron: Asymmetry 1996,
7
, 1543-1546.
5) Gimple, O.; Schreier, P.; Humpf, H.-U. Tetrahedron: Asymmetry
997, 8, 11-14.
6) (a) Prelog, V.; Wilhelm, M.; Bright, D. B. Helv. Chim. Acta 1954,
(
1
(
3
3
9
7, 221-224. (b) Lee, J . B.; Downie, I. M. Tetrahedron 1967, 23, 359-
63. (c) Mori, K.; Takigawa, T.; Matsuo, T. Tetrahedron 1979, 35, 933-
40. (d) Comprehensive Organic Chemistry; Barton, R. H. D., Ollis, D.
(10) (a) Wiesler, W. T.; Nakanishi, K. J . Am. Chem. Soc. 1989, 111,
3446-3447. (b) Wiesler, W. T.; Nakanishi, K. J . Am. Chem. Soc. 1989,
111, 9205-9213. (c) Wiesler, W. T.; Nakanishi, K. J . Am. Chem. Soc.
1990, 112, 5574-5583.
W., Eds.; Pergamon Press: Oxford, 1979; 69-106.
S0022-3263(97)01589-2 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/06/1998

A New Strategy in Exciton-Coupled CD
J . Org. Chem., Vol. 63, No. 2, 1998 323
F igu r e 1. UV and CD spectra of bichromophoric derivatives (R)-3a , (S)-3a , (R)-3b, (S)-3b, (R)-3c, and (S)-3c in acetonitrile.
Sch em e 1. Tw o-Step Der iva tiza tion of r-Hyd r oxy Ca r boxylic Acid s 1a , 1b, a n d 1c to th e Cor r esp on d in g
a
Bich r om op h or ic Der iva tives 3a , 3b, a n d 3c
a
Bold lines indicate the transition dipoles.
The stereochemical assignment of the R-hydroxy acid
moiety still remains a difficult task.
be performed in a variety of solvents; even water is useful
1
1b
for insoluble amino acids or polar fatty acids.
The
The application of ECCD to R- or â-hydroxy carboxylic
acids requires two chromophores suitable for exciton
coupling. The “bichromophoric” ECCD method utilizes
two different types of chromophores which are selectively
introduced at two different types of hydroxyls or other
functional groups.10 In this study 2(S)- and 2(R)-hydroxy-
propanoic acid (1a ), 2(R)- and 2(S)-hydroxy-3-methylbu-
tanoic acid (1b), and (R)- and (S)-cyclohexylhydroxyacetic
acid (1c) were used as model compounds. Using 9-an-
thryldiazomethane (4) carboxyl groups can be selectively
derivatized to the corresponding 9-methylanthryl esters
chiral hydroxy carboxylic acids 1a , 1b, and 1c were
derivatized with 9-anthryldiazomethane (4) to the cor-
responding 9-methylanthryl esters 2a , 2b, and 2c in
approximately 80-90% yield (Scheme 1). Since the
9-methylanthryl group may be introduced selectively to
carboxyl groups, the remaining secondary hydroxyl group
in the R-position can be derivatized with the 2-naph-
thoate or another suitable chromophore. Subsequent
treatment of the methylanthryl esters 2a , 2b, and 2c
with 2-naphthoyltriazole 512 finally gave the bichromo-
phoric derivatives 3a , 3b, and 3c (Scheme 1). Due to the
intense absorption of the 9-methylanthryl group (ꢀ )
140 000) and the 2-naphthoate chromophore (ꢀ ) 54 000),
the chromophoric derivatives are highly fluorescent,
facilitating easy purification on a small scale. The CD
and UV spectra of 3a , 3b, and 3c are shown in Figure 1.
2
(Scheme 1). The fluorescent chromophore 9-anthryl-
diazomethane (4) was developed as a fluorescent marker
for HPLC analysis of fatty acids.11 It is easily synthesized
from 9-anthraldehyde hydrazone by oxidation with ac-
tivated MnO to yield 60-70%, which can be stored for
2
several months and used whenever needed. Since 9-an-
thryldiazomethane is very reactive, the derivatization of
carboxyl groups takes only about 0.5 h and the reaction
can be easily followed by the color change from red to
light yellow. Another advantage is that the reaction can
In 9′-methylanthryl 2(R)-(2′′-naphthoyloxy)propanoate
1
[(R)-3a ] the long axis B
b
transition (Scheme 1) of the
9-methylanthryl chromophore with its quite intense
1
b
absorption couples with the B band of the 2-naphthoate
chromophore to give a positive split CD curve with
extrema at 254 nm (∆ꢀ ) +25.4) and 237 nm (∆ꢀ ) -36.4)
(
11) (a) Nakaya, T.; Tomomoto, T.; Imoto, M. Bull. Chem. Soc. J pn.
1
1
967, 40, 691-692. (b) Nimura, N.; Kinoshita, T. Anal. Lett. 1980, 13,
92-202.
(12) Schneider, C.; Schreier, P.; Humpf, H.-U. Chirality 1997, 9,
563-567.

3
24 J . Org. Chem., Vol. 63, No. 2, 1998
H o¨ r et al.
and an amplitude A of +61.8. This positive CD shows
1
b
that the electric transition dipoles ( B ) of the 9-methyl-
anthryl chromophore and the 2-naphthoate constitute a
positive chirality. The corresponding enantiomer (S)-3a
exhibits an opposite bisignate CD curve with a negative
Cotton effect at 255 nm (∆ꢀ ) -25.1) and a positive CE
at 238 nm (∆ꢀ ) +37.4), amplitude A ) -62.5. The
methylanthryl/2-naphthoate couplings in 2(R)- and 2(S)-
hydroxy-3-methylbutanoic acid derivatives (R)-3b and
(
S)-3b are depicted in Figure 1b. The exciton coupling
between the two chromophores in 9′-methylanthryl 2(R)-
2′′-naphthoyloxy)-3-methylbutanoate [(R)-3b] give rise
(
to a positive split CD curve with CEs at 253 (∆ꢀ ) +22.7)
and 237 nm (∆ꢀ ) -39.1), A ) +61.8. The corresponding
F igu r e 2. Conformational presentation of the lowest energy
conformer of (S)-3a and (R)-3a obtained after molecular
modeling conformational search using MacroModel 5.0 and
predicted sign of the first Cotton effect (bold lines indicate the
transition dipoles).
(
S)-3b enantiomer shows a similar CD curve with the
same shape but opposite signs of Cotton effects at 254
∆ꢀ ) -26.0) and 237 nm (∆ꢀ ) +36.0), with an A value
(
of -62.0. Even (R)-3c and (S)-3c with the bulky cyclo-
hexyl side chain gave similar CD spectra with opposite
Cotton effects for both enantiomers. The chromophoric
derivative (R)-3c exhibits a positive split CD curve with
extrema at 253 nm (∆ꢀ ) +32.3) and 236 nm (∆ꢀ )
Furthermore, our results are in agreement with pre-
dictions based on MM2 calculations using MacroModel
5.0.13 Figure 2 shows the preferred conformations of (S)-
3a and (R)-3a obtained after local energy minimization
and Monte Carlo conformational search. In both con-
formers the naphthoyl group adopts the s-trans confor-
mation and the ester carbonyl is almost syn with the
-
20.1), amplitude A ) +52.4. The enantiomer (S)-3c
shows a negative first Cotton effect at 254 nm (∆ꢀ )
22.4) and a positive second CE at 238 nm (∆ꢀ ) +37.8),
-
A ) -60.2 (Figure 1c). These data clearly demonstrate
that the absolute stereochemistry of R-hydroxy carboxylic
acids can be deduced from a single CD measurement. The
amplitudes of the split Cotton effects are inversely
proportional to the square of interchromophoric distance
and proportional to the square of extinction coefficients.1
Furthermore, the amplitude is dependent on the projec-
tion angle between the electric transition dipoles of the
proton at C-2, which is in agreement with the preferred
conformation of similar compounds.1
,14
The low-energy
conformations could be confirmed by NOE experiments.
The methylene hydrogens of the 9-methylanthryl group
are diastereotopic, and we observed the same NOE effect
(5%) between CH
and C-8 hydrogens of the anthryl ring. Moreover, there
is no NOE effect between the CH protons and the methyl
2 2
a and CH b and the doublet of the C-1
2
1
chromophores. There is no coupling, if the projection
group as well as the protons of the 2-naphthoate chro-
mophore. In the low-energy conformation of (S)-3a , the
two transition dipoles of the two chromophores constitute
a negative chirality (counterclockwise, see Figure 2);
therefore, the predicted S configuration is in very good
agreement with the obtained CD curve, which shows a
negative first CE at 255 nm (Figure 1a). In (R)-3a , the
chirality is positive (clockwise), leading to a positive
experimental CD couplet (Figure 1a). Similar results
were obtained for all other chromophoric derivatives.
angle is 0° or 180°, whereas coupling is maximal for a
torsion angle of about 70°. Since exciton coupling de-
pends on the interchromophoric distance and the torsion
angle between the transition dipoles of the chromophores,
the resulting CD curves are determined by the conforma-
tion of the chromophoric derivatives. Therefore, one
would expect that the R group (Scheme 1) attached to
the R-carbon affects the amplitude of the bisignate CD
curve. However, as shown with 3a , 3b, and 3c, the
amplitude of the resulting CD spectra is not much
affected by the R-group at the chiral center. For example,
the enantiomer (S)-3a (A ) -60.4) with the relatively
small methyl group yielded almost the same amplitude
as (S)-3c (A ) -62.4) with the large bulky cyclohexyl
group at the chiral center (Figure 1). Thus the preferred
sense of twist between the 9-methylanthryl and the
Theoretically, one would also expect exciton coupling
1
between the 2-naphthoate B
b
transition (ca. 240 nm) and
1
the short axis L transition (350-380 nm) of the meth-
ylanthryl chromophore (Scheme 1). However, since the
a
absorption maxima λmax are separated by more than 110
1
nm, exciton coupling is very weak or close to nil.
The above data clearly demonstrate that the two-step
derivatization using the 9-methylanthryl and the 2-naph-
thoate chromophore provides a general microscale method
for the absolute configurational assignment of R-hydroxy
carboxylic acids. The chromophoric combination of the
9-methylanthryl/2-naphthoate group leads to strong op-
posite Cotton effects with A values ranging from -62 to
2
-naphthoate follows the same CD pattern and is not
affected by the substituent attached to the stereogenic
center. If the CD curve of the bichromophoric derivative
shows negative chirality, the R-hydroxy carboxylic acid
has the S configuration and vice versa.
In addition, CD measurements of all chromophoric
derivatives were performed in hexane as an nonpolar
solvent. In hexane, however, the CD curves were almost
the same as in acetonitrile, with slight differences in the
amplitudes. All R-configured hydroxy acids (R)-3a , (R)-
+
62 for both R-hydroxy acid enantiomers. The preferred
sense of twist between the 9-methylanthryl and the
-naphthoate group in bichromophoric derivatives 3a , 3b,
2
and 3c follows the same CD pattern (negative chirality,
S configuration; positive chirality, R configuration) and
is not affected by the substituent attached to the stereo-
3
b, and (R)-3c revealed a positive first Cotton effect at
2
54 or 253 nm and a negative second CE at 236 or 237
nm (CD not shown; see Experimental Section). The
corresponding S enantiomers showed mirror image CD
spectra in hexane with extrema at about 254 nm (nega-
tive CE) and 238 nm (positive CE).
(
13) All calculations were calculated with MM2 force field in CHCl
At least 1000 conformers were searched for each simulation.
14) Dong, J .-G.; Akritopoulou-Zanze, I.; Guo, J .; Berova, N.; Na-
kanishi, K. Enantiomer In press.
3
.
(

A New Strategy in Exciton-Coupled CD
J . Org. Chem., Vol. 63, No. 2, 1998 325
genic center. The use of 9-anthryldiazomethane as a
selective reagent for carboxyl groups opens a new field
of applications of the ECCD method to many natural
products containing carboxyl groups or similar structural
units.
All other chromophoric derivatives were prepared from the
corresponding 2-hydroxy acids following the general procedure
given for 3a .
9
′-Met h yla n t h r yl 2(S)-(2′′-n a p h t h oyloxy)p r op a n oa t e
1
[
(S)-3a ]: H NMR see ref 5; EI-MS m/z 434; EI-HRMS m/z
for C29 calcd 434.1518, found 434.1510; CD (acetonitrile)
22 4
H O
2
55 nm (∆ꢀ ) -25.1), 238 nm (∆ꢀ ) +37.4); CD (hexane) 255
Exp er im en ta l Section
Gen er a l P r oced u r e. All solvents and chemicals used for
reaction were of reagent grade and were purchased from Fluka
nm (∆ꢀ ) -16.9), 236 nm (∆ꢀ ) +33.3).
9′-Meth yla n th r yl 2(S)-(2′′-n a p h th oyloxy)-3-m eth ylbu -
1
(
Neu-Ulm, FRG) or Aldrich (Steinheim, FRG). Anhydrous
ta n oa te [(S)-3b]: H NMR (400 MHz, CDCl
3
) 8.58 (s, 1H);
1
solvents were freshly distilled. H NMR spectra were recorded
in CDCl on a Bruker WM 400 MHz spectrometer and are
reported in parts per million (δ) relative to CHCl (7.26 ppm)
8.50 (s, 1H), 8.33 (d, J ) 8.8 Hz, 2H), 8.01 (d, J ) 8.4, 2H),
7.89 (m, 4H), 7.53 (m, 6H), 6.33 (d, J ) 12.5 Hz, 1H), 6.19 (d,
J ) 12.5 Hz, 1H), 5.16 (d, J ) 4.4 Hz, 1H), 2.31 (m, 1H), 1.00
3
3
as an internal reference. UV-vis and CD spectra were
recorded in acetonitrile and hexane solutions on a Shimadzu
UV-2101PC spectrophotometer and a J ASCO J -600 spectropo-
larimeter in a 1 cm cell. The exact concentration of the
solutions were determined from the UV extinction coefficients
26 4
(d, J ) 7.0 Hz, 6H); EI-MS m/z 462; EI-HRMS m/z for C31H O
calcd 462.1831, found 462.1838; CD (acetonitrile) 254 nm (∆ꢀ
) -26.0), 237 nm (∆ꢀ ) +36.0); CD (hexane) 253 nm (∆ꢀ )
-23.9), 237 nm (∆ꢀ ) +27.1).
9
′-Met h yla n t h r yl (S)-(2′′-n a p h t h oyloxy)cycloh exyl-
-
1
-1
(
methylanthryl chromophore, ꢀ254 ) 140 000 M cm ).
Syn th esis of 9-An th r yld ia zom eth a n e (4). A mixture of
1
eth a n oa te [(S)-3c]: H NMR (400 MHz, CDCl
8
4
Hz, 1H), 5.16 (d, J ) 4.4 Hz, 1H), 1.25 (m, 11H); EI-MS m/z
5
CD (acetonitrile) 254 nm (∆ꢀ ) -22.4), 238 nm (∆ꢀ ) +37.8);
CD (hexane) 255 nm (∆ꢀ ) -24.9), 237 nm (∆ꢀ ) +45.8).
3
) 8.58 (s, 1H),
.50 (s, 1H), 8.33 (d, J ) 8.8 Hz, 2H), 8.03 (m, 2H), 7.87 (m,
H), 7.53 (m, 6H), 6.32 (d, J ) 12.5 Hz, 1H), 6.19 (d, J ) 12.5
9
-anthraldehyde hydrazone (0.02 mol, commercially available
from Lancaster (M u¨ hlheim, FRG) and activated manganese
dioxide (0.08 mol) in CH Cl was stirred at 0 °C for 4 h. The
2
2
02; EI-HRMS m/z for C34 calcd 502.2144, found 502.2137;
30 4
H O
black solids were filtered off, and the filtrate was evaporated
in vacuo. The red solid residue was extracted with n-hexane
1
to yield 65% 9-anthryldiazomethane: H NMR 8.33 (s, 1H),
The corresponding enantiomers (R)-3a , (R)-3b , and (R)-
8
4
.17 (d, J ) 8.8 Hz, 2H), 8.01 (d, J ) 7.7 Hz, 2H), 7.51 (m,
3
3
c revealed the same 1H NMR and MS data as (S)-3a , (S)-
b, and (S)-3c. CD data (acetonitrile): (R)-3a , 254 nm (∆ꢀ )
H), 5.70 (s, 1H); IR (KBr) ν ) 2025 cm-1 (NdN).
Tw o-Step Syn th esis of Ch r om op h or ic Der iva tive (S)-
a . To a solution of hydroxy acid (S)-1a (0.25 mmol) in dry
+
25.4), 237 nm (∆ꢀ ) -36.4); (R)-3b, 253 nm (∆ꢀ ) +22.7),
37 nm (∆ꢀ ) -39.1); (R)-3c, 253 nm (∆ꢀ ) +32.3), 236 nm
∆ꢀ ) -20.1). CD data (hexane): (R)-3a , 254 nm (∆ꢀ ) +16.8),
34 nm (∆ꢀ ) -35.6); (R)-3b, 254 nm (∆ꢀ ) +60.8), 236 nm
3
2
diethyl ether (2.5 mL) was added a solution of 9-anthryldia-
zomethane (0.3 mmol) in dry diethyl ether (2.5 mL) dropwise.
The reaction mixture was stirred at room temperature for 30
min and concentrated under reduced pressure and the product
purified by preparative (prep) TLC (silica gel 60 F254, 2 mm,
E. Merck; solvent system: diethyl ether) to yield 80-90% of
(
2
(
-
∆ꢀ ) -64.1); (R)-3c, 255 nm (∆ꢀ ) +18.5), 234 nm (∆ꢀ )
32.7).
(
S)-2a . The anthrylmethyl ester (S)-2a (0.025 mmol) was then
Ack n ow led gm en t. These studies were supported by
treated with 2-naphthoyltriazole (0.03 mmol) and a catalytic
amount of DBU in acetonitrile (1 mL) at room temperature
for 10 h. The reaction mixture was concentrated and purified
by prep TLC [solvent system: diethyl ether/pentane (1:1)] as
described above, yielding 90% of (S)-3a .
the Deutsche Forschungsgemeinschaft Bonn, the Fonds
der Chemischen Industrie, Frankfurt, and the Univer-
sit a¨ tsbund W u¨ rzburg.
J O971589W