On the stabilization of the syn-rotamer of amino acid carbamate derivatives by hydrogen bonding

Article abstract of DOI:10.1021/jo961446u

The syn-rotamers of carbamate derivatives of α-amino acids are shown to be stabilized by the formation of H-bond complexes with carboxylic acid moieties in solution. This effect is, as expected, concentration and temperature dependent. Thermodynamic parameters (both ΔG° and ΔG?) for N-Boc-alanine were determined by NMR in the ±60 °C range.

Full text of DOI:10.1021/jo961446u

8402
J . Org. Chem. 1996, 61, 8402-8406
On th e Sta biliza tion of th e Syn -Rota m er of Am in o Acid Ca r ba m a te
Der iva tives by Hyd r ogen Bon d in g
Dana Marcovici-Mizrahi,† Hugo E. Gottlieb,* Vered Marks, and Abraham Nudelman*
Chemistry Department, Bar-Ilan University, Ramat Gan 52900, Israel
Received J uly 30, 1996X
The syn-rotamers of carbamate derivatives of R-amino acids are shown to be stabilized by the
formation of H-bond complexes with carboxylic acid moieties in solution. This effect is, as expected,
concentration and temperature dependent. Thermodynamic parameters (both ∆G° and ∆G‡) for
N-Boc-alanine were determined by NMR in the (60 °C range.
In tr od u ction
Carbamates are known to exist as syn- and anti-
rotamers (Figure 1). The latter are more stable by ca. 1
kcal/mol,1 as supported by detection of about 90% anti-
rotamers in the NMR spectra. The syn-rotamers that
exist in small quantities at room temperature are usually
difficult to identify, since their signals broaden because
of the rotation, causing their lines to blend into the base-
line (a “hidden partner”2) .
F igu r e 1. Rotamers of carbamates.
Resu lts a n d Discu ssion
In the course of our investigations, several N-Boc
derivatives of unnatural amino acids such as N-Boc-L-
vinylglycine3 (1a ) were prepared. The 1H-NMR spectrum
of 1a reveals that instead of the expected pattern for a
Boc-carbamate, where the NH proton appears at ca. 5
ppm, two different Boc-carbamates are present. One of
them displays the normal profile (NH peak at 5.20 ppm),
while the other exhibits a rather extraordinary NH* at
7.10 ppm. All remaining features of the molecule are
duplicated.
The formation of two carbamate products, wherein one
of them shows a low-field NH proton, was unexpected.
At first, it was considered that the double bond in
vinylglycine caused the abnormal behavior of the Boc-
derivative. In order to verify this assumption, the NMR
spectra of several N-Boc-amino acids (Figure 2) and
esters were taken.
The experiments were conducted with a variety of
commercially available N-Boc-amino acids (2a , 4a -6a ),
N-Boc-(4-methoxyphenyl)glycine4 (3a ), and their corre-
sponding methyl esters (prepared by reaction of the acids
with trimethylsilyl diazomethane)5 (Table 1). In order
to monitor the correlation between unsaturation and new
species formation, experiments using N-Boc-R-aminobu-
tyric acid (2a ), the saturated analog of N-Boc-vinylglycine
(1a ), and N-Boc-(4-methoxyphenyl)glycine (3a ) were also
performed.
F igu r e 2. Selected N-Boc-amino acid probes for 1H-NMR.
the new species is the major one, while in all other
probes, the new species is the minor product. However,
all of the corresponding N-Boc-amino acid esters give the
expected “normal” spectra, consistent with previous
reports of only a single species observed at room tem-
perature.1
The identification of the “unusual” species as the syn-
rotamer of the unsaturated N-Boc-amino acids was
confirmed by the strongly upfield position of the Boc
methyl resonances (1.23 ppm and 1.28 ppm vs. ca. 1.45
ppm, Table 1), attributed to shielding by the aryl or vinyl
moieties, possible only for the syn-rotamer (Figure 3).
The “special” pattern of N-Boc-amino acids is also
observed in their 13C-NMR spectra (Table 2), while the
corresponding esters once again exhibited only one
product. 13C-NMR spectra revealed duplication not only
around the CH-NH bonds, but also in more remote parts
of the molecules, such as the carbonyls of both the acids
and carbamates.
All of the N-Boc-amino acids studied form this new
species along with the regular-pattern product. For 3a
† Present address: Organic Chemistry Department, Israel Institute
for Biological Research, Ness Ziona 74100, Israel.
X Abstract published in Advance ACS Abstracts, October 15, 1996.
(1) Kost, D.; Kornberg, N. Tetrahedron Lett. 1978, 35, 3275-3276.
(2) Hassner, A.; Maurya, R.; Friedman, O.; Gottlieb, H. E.; Padwa,
A.; Austin, D. J . Org. Chem. 1993, 58, 4539-4546.
(3) Afzali-Ardakani, A.; Rapoport, H. J . Org. Chem. 1980, 45, 4817-
4820.
In order to search for the spectral features attributable
to the ester syn-rotamers, low-temperature 1H-NMR
spectra were obtained. Indeed, at -54.3 °C, an extra set
of small peaks, which broadened and disappeared above
ca. 10 °C, was observed (Table 3). Noteworthy is the fact
that the chemical shifts for the anti- and syn-NH hydro-
gens in these esters are very similar.
(4) A generous gift from Teva Labs.
(5) Hashimoto, N.; Aoyama, T.; Shioiri, T. Chem. Pharm. Bull. 1981,
29, 1475-1478.
S0022-3263(96)01446-6 CCC: $12.00 © 1996 American Chemical Society

Hydrogen Bonding of Syn-Rotamer of Amino Acid Carbamates
J . Org. Chem., Vol. 61, No. 24, 1996 8403
Ta ble 1. 1H-NMR Ch em ica l Sh ifts for N-Boc-Am in o Acid s a n d Ester s
N-Boc probe
1a
2a
2b
3a
3b
4a
4b
5a
5b
6a
6b
CH
4.90
4.30
4.25
5.26
5.30
4.34
4.32
3.98 (CH2)
3.92 (CH2)
4.25
4.21
3.92
CH*
4.70
4.10
-
5.06
-
4.18
-
3.95 (CH2)
-
4.05
-
3.83
NH
NH*
Boc (Me3C)
5.10
5.10
5.05
5.48
5.56
5.10
5.10
5.10
5.06
5.05
5.02
7.10
7.10
6.28
-
1.45 (major) + 1.28
1.45
1.43
1.42 + 1.23 (major)
1.48
1.45
1.45
1.43
1.45
1.43
1.44
7.80
-
6.73
-
6.78
-
6.16
-
4a (DMSO-d6)
6.74
1.38 + 1.35 (minor)
Ta ble 2. 13C-NMR Ch em ica l Sh ifts for N-Boc-Am in o Acid s a n d Ester s
N-Boc probe
CH
CMe3
Me3
OCO-NH
RCOO
2a
2b
3a
3b
4a
4b
5a
5b
6a
6b
54.47 + 55.77*
54.50
80.12
79.73
28.29
28.25
27.99* + 28.23
155.58
155.30
177.24
173.18
173.82* + 175.25
56.90 + 58.20*
80.31 + 81.53*
154.94 + 156.75*
56.98
79.99
28.24
28.31
28.19
28.23
28.20
28.25
28.26
154.73
171.77
177.45
173.66
49.16 + 50.27*
49.08
80.24 + 81.83*
79.66
155.47 + 156.72*
154.98
42.19 + 43.32*
80.38 + 81.77*
156.04 + 157.24*
173.95* + 174.38
42.20
79.88
155.62
170.72
176.73
172.79
58.43 + 60.11*
58.53
80.00 + 81.58*
79.68
155.82 + 157.06*
155.57
Ta ble 4. 1H-NMR Ch em ica l Sh ifts for Boc, Cbz, a n d
Am id e P r obes
probe
CH
NH
4a
4b
9a
9b
8a
8b
7
4.34 + 4.18*
4.32
4.42 + 4.34*
4.40
4.81
4.82
3.75
5.10 + 6.73*
5.10
5.39 + 6.88*
5.34
5.98
5.90
4.37
Ta ble 5. Con cen tr a tion Dep en d en ce of th e NH*
Ch em ica l Sh ift
F igu r e 3. Rotamers of (4-methoxyphenyl)glycine 3a .
probe
conc (M)
NH
NH*
K, anti/syn
4a
0.0079
0.0311
0.1619
0.0205
0.0829
0.4023
0.0179
0.0785
0.3729
0.0144
0.0772
0.3557
5.02
5.07
5.20
5.04
5.05
5.12
5.28
5.38
5.49
5.03
5.03
5.06
6.46
6.77
6.84
12
2.5
1.33
4b
9a
6b
6.36
6.63
6.90
19
7.5
2
F igu r e 4. Selected probes for 1H-NMR.
Ta ble 3. 1H-NMR Sp ectr a for Ca r ba m a te Ester s a t -54.3
°C
probe
rotamer
NH
CH
K, anti/syn
carbamate) were found to be necessary and sufficient for
this phenomenon to occur.
4b
anti
syn
anti
syn
anti
syn
5.24
5.13
5.55
5.48
5.69
5.62
4.34
4.18
4.41
4.29
5.24
5.07
12
9b
3b
8
6
Aggr ega tion Stu d ies. The low-field absorption of the
syn-NH is strongly reminiscent of the deshielded OH
resonances detected in H-bonded dimers of carboxylic
acids. To explore this possibility, concentration-depend-
1
ent H-NMR spectra of two carbamoylated amino acids
In order to explore the generality of these observations,
several related compounds were prepared (Figure 4),
whose relevant room temperature NMR data are pre-
sented in Table 4. N-Boc-isopropylamine (7), which lacks
an acid moiety, shows a single rotamer, as does an amide
probe, N-acetamidophenylalanine (8a ). However, N-Cbz-
4a and 9a and two N-Boc-esters 4b and 6b were obtained
(Table 5 and Figure 5). Indeed, the chemical shifts of
the low-field syn-rotamer NH protons are two to three
times more concentration-dependent than the NH’s of the
corresponding anti-rotamers. Moreover, these experi-
ments indicate that the proportion of the syn-rotamers
increases with concentration, supporting the existence
of an aggregation process.
1
alanine (9a ) gives a similar H-NMR spectrum to those
of the N-Boc-carbamates, showing a single rotamer for
the ester and two for the acid. In all cases, the minor
rotamer had the same low-field NH signal. Thus, the
presence of both an acid and a carbamate (not only a Boc-
Decreasing temperature offers another method for
stabilizing oligomerization. Thus, spectra of three car-
bamoylated amino acids 3a , 4a , and 9a were taken over

8404 J . Org. Chem., Vol. 61, No. 24, 1996
Marcovici-Mizrahi et al.
Ta ble 6. Tem p er a tu r e-Dep en d en t Ch em ica l Sh ift Ch a n ges for NH a n d NH*
3a 4a
NH* NH*
9a
T, °C
NH
K, anti/syn
NH
K, anti/syn
NH
NH*
K, anti/syn
-54.3
-33.1
-11.9
+9.3
+22.1
+35.2
+47.7
+62.2
5.21
5.16
5.16
5.13
5.10
5.07
5.06
5.13
7.91
7.82
7.55
7.09
6.75
6.43
6.08
0.09
0.15
0.59
1.20
1.75
2.20
5.55
5.50
5.45
5.40
5.36
5.33
5.30
5.33
8.17
8.09
7.78
7.24
6.79
6.48
0.56
0.33
0.82
5.63
5.57
5.51
5.48
5.46
5.44
5.47
8.38
8.28
8.06
7.81
7.53
7.12
6.72
0.05
0.17
0.37
0.57
1.22
2.73
2.58
F igu r e 7. Possible dimer between a syn-carbamate and an
acid group.
Ta ble 7. Acetic Acid -In flu en ced F or m a tion of Dim er s
probe
AcOH added (µL)
NH
NH*
K, anti/syn
4b
0
1.5
3
9
30
0
1.5
3
9
30
50
5.08
5.08
5.09
5.13
5.21
5.08
5.08
5.08
5.10
5.17
5.22
5.51
5.74
6.13
6.47
6.76
6.51
6.42
6.39
6.55
6.63
5.82
5.71
3.79
2.85
2.10
2.75
3.04
3.00
2.29
1.98
4a
F igu r e 5. Concentration-dependent chemical shifts of NH and
NH* in N-Cbz-alanine (9a ).
to a solution of a carbamoylated amino acid ester (Table
7). Indeed, from the first addition, the signals of the syn-
rotamer appeared, and both its concentration and the
downfield shift of its NH increased as a function of the
amount of added acid. In contrast, addition of acetic acid
to a solution of the corresponding carbamoylated amino
acid affected neither the anti/syn ratio nor the NH
chemical shifts.
In order to further confirm this hypothesis, the 1H-
spectrum of 4a was obtained in DMSO-d6. This solvent
is known to be a good H-bond acceptor and would be
expected to stabilize both the syn- and the anti-rotamers
to a similar extent. Indeed (Table 1, last entry), under
these conditions, the chemical shifts for both NH protons
are quite close and strongly indicative of H-bonding. Also,
the anti/ syn equilibrium constant (K ) 6.2) is much
higher than for the CDCl3 solution at the same temper-
ature (K ) 1.8, Table 6) and in line with the “normal”
values observed for the methyl ester (e. g. K ) 10 for 4b
in CDCl3 at room temperature).
Qu a n tita tive Mea su r em en ts. In order to obtain
more accurate measurements of both the equilibrium
constants and the rate of interconversion of the rotamers,
temperature dependent NMR spectra of N-Boc-alanine
4a over a wide range of temperatures were measured.
Full lineshape analyses were performed, fitting the
experimental spectra to lines calculated with specific rate
constants6 (Figure 8 and Table 8).
F igu r e 6. Temperature-dependent chemical shift changes for
N-Boc-alanine (4a ).
a wide range of temperatures (Table 6). In all cases as
the temperature increases, the favored rotamer switches
from syn to anti. Furthermore, the temperature coef-
ficient for the chemical shifts of the NH hydrogens was
at least 1 order of magnitude larger for the syn than the
for the anti species (ca. 2 × 10-2 vs ca. 1.5 × 10-3 ppm/
°C, respectively, Figure 6). The CH chemical shifts were
largely temperature-independent.
The above data, strongly support the notion that syn-
rotamers of N-carbamoylated amino acids form intermo-
lecularly H-bonded species. Furthermore, the OH of the
carboxylic acids must be involved in this process, since
the corresponding esters do not behave similarly. To
explain this phenomenon, we suggest the formation of a
dimer as shown in Figure 7. It seems irrelevant whether
R′′ represents a syn- or an anti-rotamer, or, for that
matter, any other substituent. In order to test this
hypothesis, increasing amounts of acetic acid were added
Con clu sion s
The switch in isomer preference mentioned above,
which occurs at ca. 0 °C, is reflected in ∆H° and ∆S° of
(6) The computer program was based on Sutherland, I. O. Annual
Reports in NMR Spectroscopy; Mooney, E. F., Ed.; Academic Press:
London, 1971; Vol. 4, p 80.

Hydrogen Bonding of Syn-Rotamer of Amino Acid Carbamates
J . Org. Chem., Vol. 61, No. 24, 1996 8405
to indicate a finite negative ∆Sq, which may imply that
the H-bond is already partially formed in the transition
state.
Exp er im en ta l Section
The NMR spectra were all recorded on a Bruker AM-300,
at 300.1 (1H) and 75.5 (13C) MHz. All spectra were taken in
CDCl3 solutions, at 24 ( 2 °C, using TMS as the internal
reference, unless otherwise indicated. The probe temperatures
were measured with a calibrated Eurotherm 840/T digital
thermometer and are believed to be accurate to 0.5 K. For
the complete line shape analysis (Figure 8 and Table 8) a
modified version of a program written by R. E. D. McClung,
University of Alberta, Edmonton, Canada T6J 262, was used.
Mass spectra were obtained on a Varian Mat 731 spectrometer
(CI ) chemical ionization). Most protected amino acids were
purchased from Sigma and were used without further purifi-
cation.
N-(ter t-Bu tyloxyca r bon yl)-L-vin ylglycin e (1a ). Di-tert-
butyl dicarbonate (0.24 g, 1.1 mmol) was added to a solution
of L-vinylglycine (1 mmol) and NaOH (0.08 g, 2 mmol) in
distilled H2O (2 mL) and tert-BuOH (4 mL). The mixture was
stirred at room temperature overnight and was then diluted
with H2O, extracted with hexane (3×), acidified to pH ) 2 (1
N KHSO4), and extracted with EtOAc (3×). The combined
EtOAc layers were dried over MgSO4, filtered, and evaporated
to give the desired N-protected product as a light yellow oil
(65% yield) (note: the product existed in the form of two
distinguishable rotamers): 1H-NMR (CDCl3) δ 1.45 (s, 9H),
4.69 and 4.91 (two m, 1H), 5.10 and 7.10 (two brd, J ) 7 Hz,
1H), 5.30 (d, J ) 10.5 Hz, 1H), 5.39 (d, J ) 17.2, 1H, CH2),
5.90 (m, 1H); 13C-NMR (CDCl3) δ 28.25, 55.68, 57.10,), 80.55,
81., 117.80, 132.31, 156.00, 173.77, 174.42; MS (CI/i-Bu) m/ e
200 (M - 1+, 3), 146 (MH+ - C4H8, 23), 102 (MH+ - C5H8O2,
100).
F igu r e 8. Calculated (left) and experimental (right) 1H-NMR
spectra of the R-H of 4a as a function of temperature.
Gen er a l P r oced u r e for th e P r ep a r a tion of Meth yl
Ester s Usin g Tr im eth ylsilyl Dia zom eth a n e.5 A 2 M
solution of TMS diazomethane in hexane (0.65 mL, 1.3 mmol)
was added dropwise to a solution of N-protected amino acid
(1 mmol) in hexane (5 mL) and dry MeOH (2 mL). The
mixture was stirred at room temperature overnight and
became cloudy. The solvent was evaporated to dryness, and
the residue dissolved in CHCl3 was washed with 5% NaHCO3.
The aqueous layer was extracted with CHCl3 (2×), and the
combined organic layers were dried over MgSO4, filtered, and
evaporated to give the desired ester. Note: Although it is not
required to wash the product with 5% NaHCO3,5 we found this
necessary, in order to obtain a clean product, without a trace
of the starting acid.
Ta ble 8. Equ ilibr iu m Con sta n ts a n d Exch a n ge Ra te for
th e Rota m er s of N-Boc-Ala n in e (4a )a
K,
anti/syn
∆G°
cal/mol
k, s-1
anti f syn
∆Gq,
kcal/mol
T, K
218.9
240.4
261.3
282.5
295.3
308.4
320.9
335.4
0.09
0.15
0.59
1.20
1.75
2.20
3.17
4.37
1061
907
277
-103
-330
-486
-740
-989
-
-
-
-
-
-
5.5
15.5 ( 0.1
15.6 ( 0.1
15.6 ( 0.2
15.8 ( 0.2
15.9 ( 0.2
16.0
52.0
105.0
300.0
a
∆H° ) 4.8 ( 0.3 kcal/mol; ∆S° ) 17 ( 1 cal/mol K.
Meth yl (2S)-2-[(ter t-Bu tyloxyca r bon yl)a m in o]bu tyr a te
(2b). Obtained as a colorless oil (57% yield): 1H NMR (CDCl3)
δ 0.91 (t, J ) 7.5 Hz, 3H), 1.43 (s, 9H,), 1.55-1.90 (m, 2H),
3.73 (s, 3H), 4.25 (q, J ) 6.8 Hz, 1H), 5.05 (d, J ) 6.2 Hz, 1H);
13C NMR (CDCl3) δ 9.55, 25.85, 28.25, 52.07, 54.50, 79.73,
the same sign, the latter being quite large, consistent
with an aggregation phenomenon. In the esters, ∆S° is
very small. Thus the value of ∆G° in N-Boc-alanine
methyl ester 4b (Table 3), 1.1 kcal/mol for the anti/syn
pair, is to a good approximation, the value of ∆H° as well,
reflecting the natural steric preference for the anti-
rotamer. If the syn- and anti-rotamers of the correspond-
ing acid have a similar enthalpy difference, then the
stabilization induced to the syn-rotamer of the acid by
the H-bond is approximately 6 kcal/mol (4.8+1.1), in
excellent agreement with other estimates of H-bonding
energies.8 The energy barrier for the rotation process is
ca. 16 kcal/mol (Table 8). Surprisingly, few quantitative
measurements of rotation barriers in carbamates have
been reported.1,7 Usually, ∆Sq for rotation of amides and
similar compounds is close to zero. Here, the data seem
155.30, 173.18; MS (CI/i-Bu) m/e 218 (MH+, 15), 203 (MH+
-
Me, 3), 186 (MH+ - MeOH, 15), 162 (MH+ - C4H8, 100), 118
(MH+ - C5H8O2, 30).
N-(ter t-Bu t yloxyca r b on yl)-L-(p -m et h oxy)p h en ylgly-
cin e Meth yl Ester (3b). Obtained as white crystals (61%
yield): 1H NMR (CDCl3) δ 1.48 (s, 9H), 3.77 (s, 3H), 3.85 (s,
3H), 5.31 (d, J ) 7.5 Hz, 1H), 5.56 (d, J ) 5.8 Hz, 1H), 6.93
(m, 2H), 7.33 (m, 2H); 13C NMR (CDCl3) δ 28.24, 52.50, 55.20,
56.98, 79.99, 114.20, 128.28, 128.91, 154.73, 159.58, 171.77;
MS (CI/i-Bu) m/e 295 (M+, 3), 239 (M+ - C4H8, 8), 179 (M+
C5H8O2, 76).
-
N-(ter t-Bu tyloxyca r bon yl)-L-a la n in e Meth yl Ester (4b).
Obtained as white crystals (50% yield): 1H NMR (CDCl3) δ
1.38 (d, J ) 7.2 Hz, 3H), 1.45 (s, 9H), 3.75 (s, 3H), 4.32 (quintet,
J ) 7.2 Hz, 1H), 5.09 (brs, 1H); 13C NMR (CDCl3) δ 18.43,
28.19, 49.08, 52.10, 79.66, 154.98, 173.66; MS (EI) m/e 203 (M+,
8), 147 (M+ - C4H8, 64), 143 (M+ - C2H4O2, 8), 103 (M+
C5H8O2, 34).
-
(7) Oki, M. Applications of Dynamic NMR Spectroscopy to Organic
Chemistry; VCH: Deerfield Beach, FL, 1985; pp 54-60.
(8) Maskill H. The Physical Basis of Organic Chemistry; Oxford
University Press: Oxford, 1985; p 148.
N-(ter t-Bu tyloxyca r bon yl)-L-glycin e Meth yl Ester (5b).
Obtained as white crystals (47% yield): 1H NMR (CDCl3) δ

8406 J . Org. Chem., Vol. 61, No. 24, 1996
Marcovici-Mizrahi et al.
1.46 (s, 9H), 3.76 (s, 3H), 3.92 (d, J ) 5.6 Hz, 2H), 5.05 (brs,
1H); 13C NMR (CDCl3) δ 28.20, 42.20, 52.06, 79.88, 155.62,
170.72; MS (CI/i-Bu) m/e 190 (MH+, 16), 134 (MH+ - C4H8,
100), 90 (MH+ - C5H8O2, 84).
N-(Ben zyloxyca r bon yl)-L-a la n in e Meth yl Ester (9b).
Obtained as a yellow oil (52% yield): 1H NMR (CDCl3) δ 1.41
(d, J ) 7.2 Hz, 3H), 3.75 (s, 3H), 4.40 (quintet, J ) 7.3 Hz,
1H), 5.12 (s, 2H), 5.34 (br d, J ) 6 Hz, 1H), 8.06 (s, 5H); 13C
NMR (CDCl3) δ 18.54, 49.56, 52.30, 66.83, 127.97, 128.03,
128.40, 136.22, 155.52, 173.32; MS (EI) m/e 237 (M+, 26), 177
(M+ - C2H4O2, 2), 107 (PhCH2+, 15), 91 (ArCH2, 100).
N-(ter t-Bu tyloxyca r bon yl)-L-va lin e Meth yl Ester (6b).
Obtained as white crystals (59% yield): 1H NMR (CDCl3) δ
0.88 (d, J ) 6.9 Hz, 3H), 0.95 (d, J ) 6.8 Hz, 3H), 1.44 (s, 9H),
2.10 (octet, J ) 6.7 Hz, 1H), 3.73 (s, 3H), 4.21 (dd, J ) 9.1, 4.8
Hz, 1H), 5.02 (d, J ) 7.8 Hz, 1H); 13C NMR (CDCl3) δ 17.59,
18.91, 28.26, 31.27, 51.91, 58.53, 79.68, 155.57, 172.79; MS
(CI/i-Bu) m/e 232 (MH+, 21), 176 (MH+ - C4H8, 70), 132 (MH+
Ack n ow led gm en t. Generous support for this work
by the Minerva Foundation and the Otto Mayerhoff
Center for the Study of Drug-Receptor Interactions at
Bar Ilan University is gratefully acknowledged.
- C5H8O2, 54), 116 (MH+ - C5H8O2 - Me, 18), 72 (MH+
C5H8O2 - MeCO2H, 100).
-
J O961446U