Total syntheses of bacillamide C and neobacillamide A; Revision of their absolute configurations

Article abstract of DOI:10.1016/j.tetasy.2013.11.001

The enantiospecific syntheses of both enantiomers of bacillamide C and neobacillamide A are described, along with the measurement of their optical activities, leading to the revision of the proposed absolute configurations of these natural products.

Full text of DOI:10.1016/j.tetasy.2013.11.001

Tetrahedron: Asymmetry 24 (2013) 1572–1575
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Total syntheses of bacillamide C and neobacillamide A; revision
of their absolute configurations
⇑
Verónica Martínez, Danilo Davyt
Cátedra de Química Farmacéutica, Departamento de Química Orgánica, Facultad de Química, Universidad de la República, Av. Gral. Flores 2124, Montevideo CP 11800, Uruguay
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 August 2013
Accepted 5 November 2013
The enantiospecific syntheses of both enantiomers of bacillamide C and neobacillamide A are described,
along with the measurement of their optical activities, leading to the revision of the proposed absolute
configurations of these natural products.
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
O
H
NH
H2N
H2N
N
S
(S)
OH
N
Several natural products containing 2-(1-aminoethyl)thiazole-
4-carboxylic acid 1 have been isolated from microorganisms
that grow in marine and terrestrial biomass (Fig. 1). This scaffold
has an asymmetric carbon atom on the
biosynthetically derives from alanine. The (S)-enantiomer of 1 is
derived from -(+)-alanine and the (R)-enantiomer from
O
N
S
1
2
- proposed structures
a-aminoethyl group that
H
H
NH
AcHN
AcHN
L
(R)
(R)
N
D
-(ꢀ)-alanine. Despite the importance of the enantiomeric forms
O
O
O
S
S
of bioactive natural products, there is widespread confusion in
the literature on this aspect of some of the metabolites containing
this moiety.
4
3
- revised structures
H
H
A tryptamine amide of 1, the alkaloid 2 (Fig. 1), having local
anesthetic action, was isolated from a thermophilic actinomycete
from the soil Thermoactinomyces strain TM-64.1 Its structure was
determined on the basis of its chemical reactions and combined
spectroscopy techniques (1H and 13C NMR, HRMS, IR). This metab-
NH
AcHN
AcHN
(S)
(S)
N
N
O
S
S
6
5
olite showed ½a 2D0
¼ ꢀ6:0 while the absolute configuration of the
ꢁ
Figure 1. Metabolites containing 2-(1-aminoethyl)thiazole-4-carboxylic acid; pro-
posed and revised structures for bacillamide C and neobacillamide A.
stereogenic center was tentatively determined as (S) by compari-
son of the circular dichroism (CD) of the N-salicylidene derivative
with N-salicylidenes of (S)-a-aryl-alkylamines (having an aryl
group instead of a thiazole). The total synthesis of 2 was performed
same as bacillamide C comparing their spectroscopic data with
those reported. However, the optical activity of microbiaretin
was not reported. In a similar manner, another metabolite was iso-
lated from a culture of Thermoactinomyces strain TA66-2 obtained
from hot-spring water. This metabolite also has the planar struc-
ture of bacillamide C, but its specific rotation was not reported.5
Neobacillamide A, a phenethylamine amide analogue of bacilla-
mide C, together with bacillamide C was isolated from a culture of
Bacillus atrophaeus C89 obtained from the marine sponge Dysidea
avara.6 Neobacillamide A was characterized as the (R)-enantiomer
from L-(+)-alanine and its configuration was confirmed as (S)
although the product obtained showed extensive racemization.2
Bacillamide C was isolated from a culture of Bacillus endophyticus
SP31 obtained on a bioassay-guided investigation from a hypersa-
line microbial mat. The bacillamide C showed ½a D24
¼ ꢀ15:2 (c
ꢁ
0.082, MeOH).3 The asymmetric carbon center of 3 was tentatively
determinated as (R) by comparison of its CD spectra with that re-
ported for 2 (Fig. 1).
Microbiaeratin was isolated from a culture of Microbispora
aerata IMBAS-11A obtained from penguin excrements collected
at the Antartic.4 The planar structure of microbiaeratin was the
by comparison of its specific rotation (½a D24
¼ ꢀ16:0) with the spe-
ꢁ
cific rotation of bacillamide C previously reported.3 The proposed
structure for neobacillamide was 4 (Fig. 1).
A total synthesis of (R)-bacillamide C from
D
-(ꢀ)-alanine was
⇑
Corresponding author. Tel.: +598 29290290.
E-mail address: ddavyt@fq.edu.uy (D. Davyt).
performed by Xu et al.,7 and a convergent synthesis of bacillamide
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.11.001

V. Martínez, D. Davyt / Tetrahedron: Asymmetry 24 (2013) 1572–1575
1573
building block in potently bioactive cyclic peptides.10 Also the
revised absolute configuration of bacillamide C and neobacillamide
NHBoc
NHBoc
CN
NHBoc
NHAc
N
a, b
c, d
e, f
S
S
CO2H 70%
66%
81%
A shows they are derived of
for genomic studies of their biosynthesis.11 Bacillamides-type
metabolites containing the scaffold 1 derived from
L-(+)-alanine; and this is important
N
8
9
7
D-(ꢀ)-alanine
CO2Et
CO2Et
NHAc
NHAc
S
have not been confirmed in the literature, however, other metabo-
lites from microorganisms containing it, such as the argyrins, have
been reported.12
3
4
S
, R = indole, yield 29%
, R = Ph, yield 73%
g
h
N
N
80%
CO2H
10
N
H
R
3. Conclusion
O
Scheme 1. Reagents and conditions: (a) NH3 (g), ClCO2Et, Et3N, THF, ꢀ10 °C; (b)
TFAA, Py, THF, rt; (c) cysteine ethylester hydrochloride, phosphate buffer pH 7,
MeOH, 60 °C; (d) DBU, BrCCl3, CH2Cl2, ꢀ10 °C; (e) TFA, CH2Cl2, rt; (f) Ac2O, Py, rt;
(g) 10% aqueous KOH, THF, rt; (h) tryptamine, HBTU, DIPEA, 0 °C to rt or
2-phenetylamine, ClCO2Et, Et3N, THF, ꢀ5 °C to rt.
In conclusion, our stereospecific syntheses of 5 and 6 from
L
-(+)-alanine via the common key intermediate 10, showed that
their spectroscopic data and optical activities were consistent with
those reported for bacillamide and neobacillamide A,
C
respectively. These results allowed us to conclude that the absolute
configuration of the natural products bacillamide C and neobacilla-
mide A should be revised to (S).
C and analogues using a chiral auxiliary was performed by Dömling
et al.8 However in both studies, the specific rotation was not
compared to the natural product nor was it reported.
In our studies on the synthesis of marine products and their
analogues our aim was to obtain (R)-bacillamide C and (R)-neoba-
4. Experimental section
4.1. General procedures
cillamide A by a stereospecific route from
D
-(ꢀ)-alanine. The total
All reagents were of reagent grade and used without further
purification unless specified otherwise. Solvents for the reactions
were distilled prior to use: THF was distilled from Na and
benzophenone, and CH2Cl2 from CaH2. All air- or moisture-
sensitive reactions were conducted under a nitrogen atmosphere
in flame-dried or oven-dried glassware with magnetic stirring.
The 1H NMR and 13C NMR spectra were recorded on a Bruker spec-
trometer operating at 400 MHz and 100 MHz, respectively. Spectra
were recorded at 25 °C in CDCl3 or DMSO-d6. 1H spectra were
referenced internally to the solvent signal (CHCl3, 7.26 ppm;
DMSO, 2.50 ppm) and 13C spectra to the solvent signal (CDCl3,
77.00 ppm; DMSO-d6, 39.52 ppm). The coupling constants J are
given in Hz. The signal patterns are indicated as follows: s = singlet,
d = doublet, dd = doublet of doublet, t = triplet, td = triplet of dou-
blet, q = quartet, m = multiplet, and br = broad. Optical rotations
were measured on a digital polarimeter using a 0.7 mL cell with
a 0.5 dm path length. Low resolution direct inlet electron impact
mass spectra (EI-MS) were taken on a Shimadzu QP 2010 plus mass
spectrometer, operating at 70 eV, and m/z ratios are reported
as values in atomic mass units. High resolution mass analyses
syntheses of both via a common key intermediate 10 are described
here in (Scheme 1). The signs of the specific rotation of the synthe-
sized compounds did not match with those reported. Both (S)-
enantiomers were also synthesized to confirm these results.
2. Results and discussion
The synthesis of the common key intermediate 10 was per-
formed by the stereospecific sequence of reactions as shown in
Scheme 1. We began this synthesis with Boc-
D-(+)-alanine having
the (R)-configuration. The Boc- -(+)-alanine led to the amide using
D
ethylchloroformate and ammonia at ꢀ10 °C, which was then con-
verted into nitrile 7 by dehydration with trifluoroacetic anhydride
and triethylamine. The condensation of 7 with cysteine ethylester
hydrochloride under buffered conditions in an aqueous methanol
medium gave the thiazoline, which then was oxidized to thiazole
8 by bromotrichloromethane and DBU.
The Boc group of 8 was hydrolyzed with trifluoroacetic acid
after which the amine was acetylated by acetic anhydride in pyri-
dine. Intermediate 10 was then obtained by alkaline hydrolysis of
ethyl ester. The (R)-bacillamide C 3 was obtained by coupling 10
with tryptamine with an HBTU reagent. The methodology to pre-
pare the thiazoline ring using a nitrile and cysteine is not a com-
(HR-MS) were performed in ESI mode taken on
a Bruker
micrOTOF-Q. HPLC analyses were conducted with a Shimadzu
instrument using a Chiralcel OD column (4.6 ꢂ 250 mm). Mobile
a
stereogenic carbon.9 The
phase for isocratic mode was
a mixture of n-hexane and
mon method for thiazoline with an
2-propanol 90:10 (v/v) for the enantiomeric analysis of 8. The
enantiomeric analyses of the bacillamides were performed using
gradient elution of n-hexane and 2-propanol, beginning with a
mixture of 90:10 (v/v) to 40:60 (v/v). Column chromatography
was carried out using silica gel (60–120 mesh or 100–200 mesh)
packed in glass columns. Technical grade ethyl acetate and
petroleum ether were used for column chromatography and were
distilled prior to use.
enantiopurity of intermediates 8 and 3 were confirmed by chiral
HPLC. The 1H NMR, 13C NMR, and HRMS data of 3 were in agree-
ment with previously reported data, however the specific rotation
of this product was ½a D24
¼ þ23:1(c 4.71, MeOH), which is the
ꢁ
opposite sign of the natural product.3Similarly (R)-neobacillamide
A 4 was prepared from intermediate 10 and 2-phenethylamine
using ethyl chloroformate as an activating agent. The spectroscopic
data of 4 were in agreement with the reported data but the specific
rotation ½a 2D4
ꢁ
¼ þ22:5(c 7.25, MeOH) was contrary to the natural
product; lit.4
½
a 2D4
ꢁ
¼ ꢀ16:0 (c 0.10, MeOH).
4.2. Synthesis of N-Boc-(R)-alanine amide
The reaction sequences were performed again, but this time
starting from Boc-
L
-(ꢀ)-alanine to obtain the (S)-enantiomers.
To a stirred solution of N-Boc-(R)-alanine (5.0 g, 26.4 mmol) in
dry THF at ꢀ10 °C, were added triethylamine (3 mL, 21.12 mmol)
and ethyl chloroformate (2.5 mL, 26.4 mmol). The reaction mixture
was stirred for 1 h and then NH3 (g) was bubbled for 1.5 h. The
mixture was then stirred at room temperature overnight. Next,
THF was removed under reduced pressure, after which NaCl sat.
sol. (40 mL) was added and extracted with EtOAc (5 ꢂ 40 mL).
The specific rotation of (S)-bacillamide C 5 was ½a D24
ꢁ
¼ ꢀ23:7 (c
ꢁ ¼ ꢀ24:1
4.99, MeOH) while that of (S)-neobacillamide A 6 was½a D24
(c 7.37, MeOH); these were in agreement with the specific
rotations of the corresponding natural products.
This result is especially important when producing bacillamide
C from cultures of Bacillus atrophaeus strain C89 to serve as a

1574
V. Martínez, D. Davyt / Tetrahedron: Asymmetry 24 (2013) 1572–1575
The organic layer was washed with HCl 0.5 M (2 ꢂ 30 mL) and
4.8. Synthesis of (R)-ethyl 2-(1-acetamidoethyl)thiazole-4-
carboxylate 9
dried over Na2SO4, filtered, and evaporated under vacuum, to give
the amide (82% yield) as a white solid; ½a D24
¼ þ36:6 (c 0.74,
ꢁ
CHCl3); dH (400 MHz, CDCl3) 6.52 (br s, 1H), 6.10 (br s, 1H), 5.30
(br s, 1H), 4.21 (br s, 1H), 1.41 (s, 9H), 1.35 (d, J 7.07 Hz, 3H); dC
(100 MHz, CDCl3) 175.32, 155.54, 80.18, 59.45, 28.28, 18.25.
The N-Boc deprotection of 8 was performed using TFA according
to the established literature method and the crude product was
acetylated with acetic anhydride and pyridine to give product 9
(84% yield last 2steps) as a brown oil; ½a D24
¼ þ29:1 (c 0.47, CHCl3);
ꢁ
4.3. Synthesis of N-Boc-(S)-alanine amide
mmax (NaCl) 3264 (br), 2985, 1720, 1655, 1373, 1219, 1022,
764 cmꢀ1; dH (400 MHz, CDCl3) 8.09 (s, 1H), 6.66 (m, 1H), 5.42
(p, J 7.05 Hz, 1H), 4.41 (q, J 7.11 Hz, 2H), 2.05 (s, 3H), 1.63 (d, J
6.93 Hz, 3H), 1.39 (t, J 7.11 Hz, 3H), dC (100 MHz, CDCl3): 172.67,
170.22, 161.13, 146.81, 127.37, 61.55, 47.20, 22.97, 21.72, 14.28.
The procedure 4.2 was performed using N-Boc-(S)-alanine to
give the amide (89% yield); ½a D24
ꢁ
¼ ꢀ37:5(c 0.77, CHCl3). The 1H
and 13C NMR spectra were identical with those of N-Boc-(R)-alanine
amide.
4.9. Synthesis of (S)-ethyl 2-(1-acetamidoethyl)thiazole-4-
carboxylate
4.4. Synthesis of N-Boc-(R)-alanine nitrile 7
To
a stirred solution of N-Boc-(R)-alanine amide (3.0 g,
The procedure in Section 4.8 was performed using (S)-8 to give
15.94 mmol) in dry THF was added dry pyridine (5.15 mL,
63.76 mmol). The trifluoroacetic anhydride (4.4 mL, 31.76 mmol)
was then added at 0 °C. The reaction mixture was then stirred for
2 h. Next, THF was removed under reduced pressure. The concen-
trate was dissolved in EtOAc (40 mL), washed with HCl 0.5 M
(5 ꢂ 20 mL), half-satd aq NaHCO3 solution (20 mL) and dried over
Na2SO4. The solvent was evaporated under vacuum, to give 7
(85% yield) as a yellow solid; dH (400 MHz CDCl3) 4.81 (br s, 1H),
4.61 (br s, 1H), 1.54 (d, J 7.2 Hz, 3H), 1.46 (s, 9H); dC (100 MHz
CDCl3) 154.04, 119.49, 81.27, 37.58, 28.20, 19.59.
the corresponding acetamide (91% yield last 2 steps) as a brown
oil; ½a 2D4
ꢁ
¼ ꢀ50:5 (c 0.45, CHCl3). The IR spectra, 1H and 13C NMR
spectra were identical to those of 9.
4.10. Synthesis of (R)-2-(1-acetamidoethyl)thiazole-4-carboxylic
acid 10
To a solution of thiazole 9 (0.085 g, 0.35 mmol) in THF (2 mL),
was added KOH 10% (2 mL), and the reaction mixture was stirred
for 1 h at room temperature. The solvent was evaporated in vacuo.
To the resulting solution was added H2O (5 mL), after which it was
acidified to pH 1–2 with HCl (6 M) and extracted with EtOAc
(15 mL ꢂ 3), dried over Na2SO4, and evaporated under vacuum, to
give 10 (74% yield) as a yellow oil; dH (400 MHz, (CD3)2CO) 8.29
(s, 1H); 7.90 (m, 1H), 5.32 (m, 1H), 1.97 (s, 3H), 1.57 (d,
J = 7.04 Hz, 3H); dC (100 MHz, (CD3)2CO) 176.68, 171.04, 163.21,
148.85, 129.65, 48.84, 23.66, 21.71.
4.5. Synthesis of N-Boc-(S)-alanine nitrile
The procedure in Section 4.4 was performed using
N-Boc-(S)-alanine amide to give the corresponding nitrile (87%
yield). The 1H and 13C NMR spectra were identical with those of
N-Boc (R)-alanine nitrile.
4.6. Synthesis of (R)-ethyl 2-(1-(tert-butoxycarbonylamino)
ethyl)thiazole-4-carboxylate 8
4.11. Synthesis of (S)-2-(1-acetamidoethyl)thiazole-4-carboxylic
acid
Cysteine ethyl ester (1.60 g, 8.68 mmol) and
7 (1.13 g,
The procedure in Section 4.10 was performed using (S)-thiazole
9 to give the corresponding acid (S)-10 (72% yield) as a yellow oil.
The 1H and 13C NMR spectra were identical with those of (R)-10.
6.63 mmol) were dissolved in a 1 M sodium phosphate buffer pH
7 (5 mL) and degassed by bubbling nitrogen for 10 min. The reac-
tion mixture was then stirred at room temperature for 3 h. The
reaction mixture was extracted with EtOAc (3 ꢂ 20 mL). The or-
ganic layer was dried over Na2SO4 and the solvent was evaporated
in vacuo, to give a crude product. The residue was purified by flash
chromatography (EtOAc/PE; 40:60) to give the thiazoline. To a
solution of the thiazoline (1.35 g, 4.46 mmol) in dry CH2Cl2
(20 mL), at ꢀ20 °C was added BrCCl3 (1.7 mL, 16.96 mmol) and
the reaction mixture was stirred for 15 min. The DBU (2.5 mL,
19.96 mmol) was then added and the reaction mixture was stirred
for an additional 2 h. The CH2Cl2 was evaporated under vacuum, to
give a crude product, which was purified by flash chromatography
4.12. Synthesis of (R)-(N-(2-(1H-indol-3-yl)ethyl)-2-(1-acetami-
doethyl)thiazole-4-carboxamide 3
To a solution of 10 (0.081 g, 0.38 mmol) and tryptamine
(0.073 g, 0.45 mmol) in dry CH2Cl2, at 0 °C were added HBTU
(0.171 g, 0.45 mmol), DIPEA (0.15 mL, 0.84 mmol), and 4-DMAP
(cat.). The reaction mixture was then warmed up to room temper-
ature, and stirred for 6 h. To the resulting solution was added HCl
5% (10 mL) and it was extracted with EtOAc (20 mL ꢂ 3). The
organic layer was washed with NaHCO3 solution, dried over Na2-
SO4, and the solvent was evaporated under vacuum to give the
crude product, which was purified by flash chromatography
(EtOAc/PE/MeOH; 30:70:5) to give 3 (29%) as a light brown oil;
(EtOAc/PE; 40:60) to give
8 (79% yield), as a brown oil;
½
a 2D4
ꢁ
¼ þ11:3 (c 0.65, CHCl3); dH (400 MHz, CDCl3) 8.06 (s, 1H),
5.25 (s, 1H), 5.08 (m, 1H), 4.39 (q, J = 7.12 Hz, 2H), 1.60 (d,
J = 6.91 Hz, 3H), 1.42 (s, 9H), 1.37 (t, J = 7.13 Hz, 3H); dC
(100 MHz, CDCl3): 174.93, 161.35, 154.88, 147.17, 127.16, 80.24,
61.43, 48.92, 28.30, 21.75, 14.36; MS ID 300.10, found 300.11
½
a 2D4
ꢁ
¼ þ23:1 (c 4.71, MeOH); mmax (NaCl) 3283 (br), 2978, 1928,
1655, 1547, 1493, 1439, 1265, 1042, 741 cmꢀ1; dH (400 MHz,
DMSO-d6) 10.83 (s, 1H), 8.71 (d, J 7.6 Hz, 1H), 8.40 (t, J 6.0 Hz,
1H), 8.12 (s, 1H), 7.61 (d, J 7.9 Hz, 1H), 7.33 (d, J 8.05 Hz, 1H),
7.18 (d, J 2.3 Hz, 1H), 7.06 (m, 1H), 6.98 (m, 1H), 5.15 (p, J 7.1 Hz,
1H), 3.54 (dd, J 14.6, 6.6 Hz, 2H), 2.94 (m, 2H), 1.90 (s, 3H), 1.50
4.7. Synthesis of (S)-ethyl 2-(1-(tert-butoxycarbonylamino)
ethyl)thiazole-4-carboxylate
(d, J 7.0 Hz, 3H); d (100 MHz, DMSO-d6) 175.02, 169.04, 160.29,
The procedure in Section 4.6 was performed using
v
149.68, 136.18, 127.15, 123.12, 122.50, 120.88, 118.32, 118.14,
111.65, 111.28, 46.66, 39.78, 25.23, 22.40, 20.38; HRMS ESI:
MH+, found 357.1387. C18H21N4O2S requires 357.1385.
N-Boc-(S)-alanine nitrile to give the corresponding thiazole (95%
yield) as a brown oil; ½a D24
ꢁ
¼ ꢀ11:7 (c 1.05, MeOH). The 1H and
13C NMR spectra were identical with those of 8.

V. Martínez, D. Davyt / Tetrahedron: Asymmetry 24 (2013) 1572–1575
1575
4.13. Synthesis of bacillamide C, (S)-(N-(2-(1H-indol-3-yl)ethyl)-
4.15. Synthesis of neobacillamide A, (S)-(N-(2-phenethyl)-2-(1-
2-(1-acetamidoethyl)thiazole-4-carboxamide 5
acetamidoethyl)thiazole-4-carboxamide 6
The procedure in Section 4.12 was performed using acid (S)-10
The procedure 4.14 was performed using the acid (S)-10 to give
to give 5 (68%) as light brown oil; ½a D24
ꢁ
¼ ꢀ23:6 (c 4.99, MeOH). The
6 (94%) as a light brown oil; ½a D24
¼ ꢀ24:1 (c 7.37, MeOH). The IR,
ꢁ
IR, HRMS ESI, 1H, and 13C NMR spectra were identical with those of
HRMS ESI, 1H, and 13C NMR spectra were identical with those of
3 and with those reported for bacillamide C.
4 and with those reported for neobacillamide A.
Acknowledgments
4.14. Synthesis of (R)-(N-(2-phenethyl)-2-(1-acetamidoethyl)
thiazole-4-carboxamide 4
The authors thank CSIC—UdelaR (Csic grupos N° 654) for fund-
ing and Alejandra Rodríguez, Polo Tecnológico de Pando for HRMS.
To a solution of 10 (0.15 g, 0.55 mmol) in dry THF at ꢀ5 °C,
were added Et3N (0.08 mL, 0.55 mmol) and ethyl chloroformate
(0.05 mL, 0.55 mmol). The reaction mixture was then stirred for
1 h, and warmed to room temperature. The 2-phenylethanamine
(0.08 g, 0.66 mmol) was added and the reaction mixture was stir-
red at room temperature overnight. The EtOAc (15 mL) was
added, and washed with KHCO3 5% (15 mL), H2O (15 mL), HCl
5% (15 mL), and H2O (15 mL), dried over Na2SO4 and the solvent
was evaporated under vacuum to give the crude product, which
was purified by flash chromatography (EtOAc/PE; 30:70), to give
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4 (73%) as a light brown oil; ½a D24
¼ þ22:5 (c 7.25, MeOH); mmax
ꢁ
(NaCl) 3267 (br), 2932, 2859, 1655, 1543, 1493, 1447, 1254,
1042, 748 cmꢀ1; dH (400 MHz, CDCl3) 8.02 (s, 1H), 7.34 (m, 3H),
7.26 (m, 3H), 6.12 (d, J 7.9 Hz, 1H), 5.36 (m, 1H), 3.70 (ddd, J
13.3, 7.1, 2.1 Hz, 2H), 2.93 (t, J 7.1 Hz, 2H), 2.06 (s, 3H), 1.59 (d,
J
6.9 Hz, 3H); dC (100 MHz, CDCl3) 172.41, 169.46, 160.89,
149.66, 138.82, 128.83, 128.62, 126.54, 123.16, 47.02, 40.55,
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2002, 55, 543–551.
35.84, 23.23, 21.38. HRMS ESI: MHꢀ, found 316.11224.
C16H18N3O2S requires 316.11197.