A Facile Synthesis of Thioacids from N -Acylbenzotriazoles

Article abstract of DOI:10.1055/s-0033-1340292

Protected amino/peptide thioacids have been synthesized in pure form in excellent yields and with retention of chirality by using protected aminoacyl- and peptidoylbenzotriazoles as active intermediates. Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0033-1340292

LETTER
▌247
lAetteFr acile Synthesis of Thioacids from N-Acylbenzotriazoles
Facile Synthesis of Thioacids from N-Acylbenzotriazoles
Ravil Khaybullin,a Siva S. Panda,a Abdulrahman O. Al-Youbi,b Alan R. Katritzky*a,b
a
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA
b
Chemistry Department, King Abdulaziz University, Jeddah 21589, Saudi Arabia
Fax +1(352)3929199; E-mail: katritzky@chem.ufl.edu
Received: 19.09.2013; Accepted after revision: 22.10.2013
acids. It is well known that N-protected thioamino acids
tends to be unstable due to their tendency toward oxida-
tion.10 We found that N-protected amino/peptide thioacids
are quite stable in pure solid form at 0 °C for at least sev-
eral months, but are easily decomposed in solution. Hence
prolonged reaction time/purification may result in a de-
crease of thioacid yield.
Abstract: Protected amino/peptide thioacids have been synthesized
in pure form in excellent yields and with retention of chirality by us-
ing protected aminoacyl- and peptidoylbenzotriazoles as active in-
termediates.
Key words: amino acids, peptides, chirality, thioacids, benzotri-
azole methodology
Perhaps the most convenient method for the synthesis of
amino thioacids is a mixed anhydride activation carboxyl-
ic group (i.e. with IBCF). In this case highly reactive
mixed anhydride intermediates cannot be isolated, and
may cause additional formation of by-products in more
complex cases. Thus mixed anhydride activation of the
carboxylic group in a guanidine-protected arginine favors
lactam by-product formation.21,22 Herein, we report a nov-
el efficient approach towards the synthesis of N-protected
amino/peptide thioacids from N-protected aminoac-
yl/peptidoyl benzotriazoles in good yield with a simple
isolation procedure and retention of chirality.
Thioacids are one of the most versatile analogues of car-
boxylic acids. Replacement of carboxyl by thiocarboxyl
group provides an important class of organic compounds
that have found wide significance. Thus thioacids undergo
useful reactions with azides,1,2 isonitriles,3,4 amines5 and
alkyl halides.6 More recently coupling of thioacids and di-
thiocarbamate terminal amines has been investigated.7
Thioacids are more acidic and tend to be more soluble
than their oxygen analogues. Their increased nucleophi-
licity makes them attractive for the design of complex
molecules particularly for the purpose of peptide liga-
tions.8
N-Protected aminoacyl benzotriazoles are stable crystal-
line compounds and have been extensively used in our
group for various nucleophilic acyl substitution reactions
under mild conditions.23,24 Moreover, it was proved earlier
that these reactions take place without racemization23–25
and provide powerful tool for the amide bond construction
with retention of chirality at an asymmetric carbon at-
om.26–28
Previous syntheses of N-protected amino thioacids in-
clude reaction of activated derivatives of carboxylic acids
such as acid halides,9 N-hydroxysuccinimide esters,8,10 or
mixed anhydrides.11 Alternatively, propylphosphonic an-
hydride (T3P)12 or CDI may be used as a coupling
reagent1,13 with hydrosulfide anion generated from H2S or
the corresponding alkali salt (Na2S, NaHS or Li2S). Large
peptide thioacids are generally synthesized by solid-phase
peptide synthesis (SPPS) on a thioester solid support14 and
Kaiser’s oxime resin with hexamethyldisilathiane.15 An-
other approach includes prior coupling of the carboxylic
acid with either HSFmoc, HSTrt, or HSTmob and subse-
quent removal of the protecting group with formation of
the corresponding thioacid.16 Lawesson’s reagent17,18 and
the carbodiimide19 method may also be used.
We first developed a standard procedure for the prepara-
tion of thioacids from N-acylbenzotriazoles. A standard
experimental protocol was developed in order to ascertain
the scope of the reaction. For this purpose, Cbz-protected
L-alanine was chosen as a model acid component, which
was easily converted into the corresponding benzotriazole
derivative 1. One of the advantages of N-acylbenzotri-
azoles is good solubility in the wide range of organic sol-
vents. Thus a stirred 0.1 M solution of benzotriazolide
(1.0 equiv) in organic solvent in the presence of base (1.0
equiv) was treated with a slow stream of H2S (bubbled for
ca. 5 min) at 0 °C. The reaction mixture was allowed to
warm to 20 °C and stirred until the starting material was
consumed (TLC control). Bases pyridine, NMM, Et3N,
DIPEA, and DBU were tested in polar (THF, MeCN) and
nonpolar (CH2Cl2) solvents (Table 1). Pyridine gave un-
satisfactory results needing prolonged reaction time, giv-
ing low yield and by-products. However strong bases
(e.g., DBU or DIPEA) completed the reaction within ten
minutes and triethylamine and NMM required 30 minutes
at 20 °C (Scheme 1). The reaction was stirred for an addi-
These diverse synthetic approaches have drawbacks. If a
carbodiimide is used, N-acylureas can be a major by-prod-
uct, whereas without additives (HOBt, CuCl2) significant
racemization may occur.20 From this point of view a re-
cently published method using EDC/Na2S in DMF for the
synthesis of N-protected amino/peptide thioacids is not
promising.19 Use of Lawesson’s reagent required column
chromatographic purification of the obtained thioamino
SYNLETT 2014, 25, 0247–0250
Advanced online publication: 16.12.2013
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1340292; Art ID: ST-2013-S0893-L
© Georg Thieme Verlag Stuttgart · New York

248
R. Khaybullin et al.
LETTER
O
O
H
H2S, base
H
O
N
O
N
N
N
SH
solvent, 20 °C
O
N
O
2
1
concentration of Cbz-L-Ala-Bt in THF solution: 0.1 M
amount of base: 1 equiv
Scheme 1 Optimization reaction for Cbz-L-Ala-SH 2
tional 30 minutes at 20 °C then nitrogen was bubbled HCl (1–2 N). In most cases pure thioacids were obtained
through the system to remove excess H2S. The results are after evaporation of solvent or crystallization from pen-
summarized in Table 1.
tane–Et2O solution.29
This procedure provides pure N-protected amino thioac-
ids (elemental analysis). Moreover Cbz-L-Agr(NO2)-SH
2d was obtained in good yield without formation of lac-
tam which occurs with other methods of activation of ar-
ginine carboxylic group.21
Table 1 Optimization of Reaction Conditions for the Preparation of
Cbz-L-Ala-SH 2
Entry
Base
Solvent
Reaction timea Yield (%)b
1
2
3
4
5
6
7
8
No base
Et3N
THF
6 h
0
>95
>95
>95
>95
50
O
THF
30 min
30 min
10 min
10 min
16 h
O
H
H
N
H2S, NMM
N
Pg
SH
NMM
DBU
THF
Pg
N
N
THF, 20 °C, 1 h
R
R
N
THF
1a–h, 1a + 1a'
2a–h, 2a + 2a'
DIEPA
pyridine
NMM
NMM
THF
Scheme 2 Preparation of N-protected amino thioacids 2a–h
THF
MeCN
CH2Cl2
30 min
2 h
>95
85
In order to explore the method further, several peptide
thioacids were synthesized. Benzotriazole activated N-
protected α-di- and tripeptides were prepared by our pre-
vious method.24 These benzotriazolides were converted
into the corresponding thioacids in good yields (Scheme
3, Table 3). The stability of thioacids in solution is poor
compared to the N-protected amino acids but both are sta-
ble in the solid state. Thus, peptide thioacids 4a–d were
kept as crystalline solids which did not change during
weeks at 0 °C.29
a For the reaction time take time when Bt-compound was completely
reacted (TLC).
b Calculated by NMR data of reaction mixture after workup.
For the preparation of N-protected α-aminoacyl thioacid,
the standard experimental protocol involved bubbling of
H2S through a precooled (0 °C) 0.1 M N-protected α-ami-
noacylbenzotriazole (1.0 equiv), NMM (1 equiv) in THF
for five minutes and then stirring at 20 °C for one hour
(Scheme 2, Table 2). The benzotriazole formed during
this reaction was easily removed by washing with dilute
In conclusion, we have reported a novel, facile method for
the synthesis of protected amino/peptide thioacids. The
reaction conditions were optimized at 20 °C for 30 min-
utes in the presence of H2S and NMM.
Table 2 Preparation of N-Protected Amino Thioacids 2a–h
Entry
Thioacid, 2
Yield (%)
Mp (°C)
Lit. mp
[α]20
D
1
2
3
4
5
6
7
8
9
Cbz-L-Ala-SH, 2a
Cbz-DL-Ala-SH, 2a + 2a′
Cbz-Gly-SH, 2b
92
93
91
78
84
86
91
88
85
77–78
74–7610
–11.1 (c = 1.0, MeOH)
racemic
65–66
data not provided
data not provided
gum13
97–98.5
gum
–
Cbz-L-Val-SH, 2c
Cbz-L-Agr(NO2)-SH, 2d
Cbz-L-Trp-SH, 2e
Cbz-L-Phe-SH, 2f
–13.1 (c = 2.1, MeOH)
–9.0 (c = 0.5, MeOH)
–44.5 (c = 0.2, MeOH)
–36.8 (c = 0.5, MeOH)
–6.1 (c = 0.2, MeOH)
–40.9 (c = 1.0, MeOH)
153–155
114–115
92.5–93.5
118–120
88.5–90
Novel
Novel
91–9319
Fmoc-L-Ala-SH, 2g
Fmoc-L-Phe-SH, 2h
78–7919
Data not provided
Synlett 2014, 25, 247–250
© Georg Thieme Verlag Stuttgart · New York

LETTER
Facile Synthesis of Thioacids from N-Acylbenzotriazoles
249
R2
O
R2
O
H
H2S, NMM
Pg
H
N
Pg
N
N
SH
N
N
N
H
H
O
R1
THF, 20 °C, 1 h
O
R1
N
n = 1,2
n = 1,2
4a–d
3a–d
Scheme 3 Preparation of N-protected di- and tripeptide thioacids 4a–d
Table 3 Preparation of N-Protected Dipeptide Thioacids 4a–c and Tripeptide Thioacid 4d
Entry
Thioacid 4
Yield (%)
Mp (°C)
[α]20
D
1
2
3
4
Cbz-L-Ala-Gly-SH, 4a
Cbz-L-Val-Gly-SH, 4b
Cbz-L-Ala-Phe-SH, 4c
Cbz-L-Ala-L-Phe-Gly-SH, 4d
87
73
79
69
100–102
159–161
107–109
162–163
nd
–25.2 (c = 0.5, MeOH)
–17.9 (c = 0.14, MeOH)
–31.4 (c = 0.5, MeOH)
(17) Pedersen, B. S.; Nilsson, N. H.; Lawesson, S. O. Bull. Soc.
Chim. Belg. 1978, 87, 223.
(18) Rao, Y.; Li, X.; Nagorny, P.; Hayashida, J.; Danishefsky,
S. J. Tetrahedron Lett. 2009, 50, 6684.
(19) Vishwanatha, T. M.; Samarasimhareddy, M.; Sureshbabu,
V. V. Synlett 2012, 89.
(20) Miyazawa, T.; Otomatsu, T.; Fukui, Y.; Yarnada, T.;
Kuwata, S. Chem. Commun. 1988, 419.
Acknowledgement
We thank the University of Florida and the Kenan Foundation for
financial support. This paper was also funded in part by generous
support from King Abdulaziz University, under grant No. D-
006/431. The authors, therefore, acknowledge the technical and fi-
nancial support of KAU. We also thank Dr. C. D. Hall for helpful
suggestions.
(21) Juliano, L.; Juliano, M. A.; Miranda, A.; De, S.; Tsuboi,
O. Y. Chem. Pharm. Bull. 1987, 35, 2550.
(22) Cezari, M. H. S.; Juliano, L. Pept. Res. 1996, 9, 88.
(23) Bajaj, K.; Panda, S. S.; Ibrahim, M. A.; El-Feky, S. A.;
Katritzky, A. R. J. Pep. Sci. 2013, 19, 110.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
m
iotSrat
ungIifoop
r
t
(24) Bajaj, K.; Panda, S. S.; El-Nachef, C.; Katritzky, A. R.
Chem. Biol. Drug Des. 2012, 80, 17.
References and Notes
(1) Mckervey, M. A.; O’Sullivan, M. B.; Mayers, P. L.; Green,
R. H. Chem. Commun. 1993, 94.
(25) Katritzky, A. R.; Angrish, P.; Todadze, E. Synlett 2009,
2392.
(2) Shangguna, N.; Katukojvala, S.; Greenberg, R.; Williams,
L. J. J. Am. Chem. Soc. 2003, 125, 7754.
(26) Katritzky, A. R.; Meher, G.; Narindoshvili, T. J. Org. Chem.
2008, 73, 7153.
(3) Wang, T.; Danishefsky, S. J. Proc. Natl. Acad. Sci. U.S.A.
2013, 110, 11708.
(27) Katritzky, A. R.; Khelashvili, L.; Munawar, M. A. J. Org.
Chem. 2008, 73, 9171.
(4) Wu, X.; Stockdill, J. L.; Wang, P.; Danishefsky, S. J. J. Am.
Chem. Soc. 2010, 132, 4098.
(28) Panda, S. S.; Hall, C. D.; Scriven, E.; Katritzky, A. R.
Aldrichimica Acta 2013, 46, 43.
(5) Mali, S. M.; Jadhav, S. V.; Gopi, H. N. Chem. Commun.
2012, 7085.
(6) Fu, X.; Jiang, S.; Li, C.; Xin, J.; Yang, Y.; Ji, R. Bioorg.
Med. Chem. Lett. 2007, 17, 465.
(7) Chen, W.; Shao, J.; Hu, M.; Yu, W.; Giulianotti, M. A.;
Houghten, R. A.; Yu, Y. Chem. Sci. 2013, 4, 970.
(8) Yamashito, D.; Blake, J. Int. J. Pept. Prot. Res. 1981, 18,
383.
(9) Kobayashi, Y.; Itabashi, K. Synthesis 1985, 671.
(10) Mitin, Y. V.; Zapelova, N. P. Int. J. Pept. Prot. Res. 1990,
35, 352.
(11) Cronyn, M. W.; Jiu, J. J. Am. Chem. Soc. 1952, 74, 4726.
(12) Madhu, C.; Basavaprabhu Vishwanatha, T. M.; Sureshbabu,
V. V. Tetrahedron Lett. 2012, 53, 1406.
(13) Lehmann, J.; Linden, A.; Heimgartner, H. Helv. Chim. Acta
1999, 82, 888.
(14) Zhang, X.; Lu, X.; Liu, C. Tetrahedron Lett. 2008, 49, 6122.
(15) Schwabacher, A. W.; Maynard, T. L. Tetrahedron Lett.
1993, 34, 1269.
(29) General Procedure: H2S was bubbled through a precooled
(0 °C) solution of N-protected α-aminoacylbenzotriazole
(1.0 mmol), NMM (1 mmol) in THF (10 mL) for 5 min. The
reaction mixture was allowed to warm at r.t. and stirred for
an additional 1 h, diluted with Et2O (25 mL) and washed
several times with 2 N HCl. The organic layer was dried
(MgSO4), the solvent was removed, and the residue was
crystallized from pentane–Et2O to give the desired thioacids.
(S)-2-{[(Benzyloxy)carbonyl]amino}-5-(2-nitroguani-
dino)pentanethioic S-Acid [Cbz-L-Agr(NO2)-SH, 2d;
Table 2, Entry 5]: white microcrystals (yield: 84%); mp
153–155 °C; [α]20D –9.0 (c = 0.5 in MeOH). 1H NMR (300
MHz, DMSO-d6): δ = 8.47 (s, 1 H), 7.79–8.14 (m, 3 H),
7.30–7.42 (m, 5 H), 5.04–5.21 (m, 2 H), 4.28–4.41 (m, 1 H),
3.07–3.22 (m, 2 H), 1.51–1.82 (m, 4 H). 13C NMR (75 MHz,
DMSO-d6): δ = 196.3, 159.4, 156.3, 136.7, 128.5, 128.0,
127.8, 66.1, 63.6, 60.9, 32.5, 28.0. Anal. Calcd for
C14H19N5O5S: C, 45.52; H, 5.18; N, 18.96. Found: C, 45.85;
H, 5.15; N, 18.62.
(16) Crich, D.; Bowers, A. A. Org. Lett. 2007, 9, 4423.
2-{[(Benzyloxy)carbonyl]amino}propanethioic S-Acid
(Cbz-DL-Ala-SH, 2a + 2a′; Table 2, Entry 2): white
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 247–250

250
R. Khaybullin et al.
LETTER
microcrystals (yield: 93%); mp 65–66 °C. 1H NMR (300
MHz, CDCl3): δ = 7.28–7.40 (m, 5 H), 5.15 (br s, 2 H), 5.30–
5.44 (m, 1 H), 4.36–4.50 (m, 1 H), 1.42 (d, J = 7.1 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 200.2, 155.7, 136.1, 128.7,
128.4, 128.3, 77.2, 67.4, 57.7, 18.2. Anal. Calcd for
C10H13NO3S: C, 55.21; H, 5.48; N, 5.85. Found: C, 55.58; H,
5.11; N, 5.62.
2-{[(Benzyloxy)carbonyl]amino}ethanethioic S-Acid
(Cbz-Gly-SH, 2b; Table 2, Entry 3): colorless needles
(yield: 91%); mp 97–98.5 °C. 1H NMR (300 MHz, CDCl3):
δ = 7.29–7.40 (m, 5 H), 5.32–5.48 (m, 1 H), 5.15 (br s, 2 H),
4.12 (d, J = 5.9 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ =
196.5, 136.5, 129.2, 128.92, 128.7, 77.6, 68.1, 52.4. Anal.
Calcd for C10H11NO3S: C, 53.32; H, 4.92; N, 6.22. Found: C,
53.32; H, 4.98; N, 6.24.
(S)-2-{[(Benzyloxy)carbonyl]amino}-3-(1H-indol-3-
yl)propanethioic S-Acid (Cbz-L-Trp-SH, 2e; Table 2,
Entry 6): white microcrystals (yield: 86%); mp 114–115 °C;
[α]20D –44.5 (c = 0.2 in MeOH). 1H NMR (300 MHz,
CDCl3): δ = 8.09 (br s, 1 H), 7.57 (d, J = 7.7 Hz, 1 H), 7.29–
7.39 (m, 6 H), 7.19–7.25 (m, 1 H), 7.01–7.06 (m, 1 H), 5.21–
5.31 (m, 1 H), 5.11 (br s, 2 H), 4.67–4.79 (m, 1 H), 3.31 (d,
J = 5.6 Hz, 2 H). 13C NMR (75 MHz, CDCl3): δ = 200.5,
156.0, 136.3, 128.6, 128.4, 128.2, 123.4, 122.5, 120.0,
118.7, 114.6, 111.5, 109.1, 68.1, 67.4, 62.2, 27.7, 25.7. Anal.
Calcd for C19H18N2O3S: C, 64.39; H, 5.12; N, 7.90. Found:
C, 64.62; H, 5.23; N, 7.70.
(S)-2-[{[(9H-Fluoren-9-yl)methoxy]carbonyl}amino]-3-
phenylpropanethioic S-Acid (Fmoc-L-Phe-SH, 2h; Table
2, Entry 9): white microcrystals (yield: 85%); mp 88.5–90
°C; [α]20D –40.9 (c = 1.0 in MeOH). 1H NMR (300 MHz,
CDCl3): δ = 7.73–7.78 (m, 2 H), 7.47–7.56 (m, 2 H), 7.35–
7.43 (m, 2 H), 7.25–7.34 (m, 5 H), 7.12–7.19 (m, 2 H), 5.14–
5.25 (m, 1 H), 4.59–4.72 (m, 1 H), 4.35–4.49 (m, 2 H), 4.18
(t, J = 6.8 Hz, 1 H), 2.96–3.21 (m, 2 H). 13C NMR (75 MHz,
CDCl3): δ = 199.4, 155.7, 143.7, 141.4, 135.2, 129.4, 129.0,
127.9, 127.6, 127.2, 125.1, 120.1, 77.2, 67.3, 62.5, 47.2,
37.7. Anal. Calcd for C24H21NO3S: C, 71.44; H, 5.25; N,
3.47. Found: C, 71.73; H, 5.12; N, 3.90.
(S)-2-[2-{[(Benzyloxy)carbonyl]amino}propanamido]-
ethanethioic S-Acid (Cbz-L-Ala-Gly-SH, 4a; Table 3,
Entry 1): white microcrystals (yield: 87%); mp 100–102 °C.
1H NMR (300 MHz, CD3OD): δ = 7.23–7.40 (s, 5 H), 5.01–
5.16 (m, 2 H), 4.80 (m, 1 H), 4.14–4.25 (m, 1 H), 3.99–4.13
(m, 1 H), 1.37 (d, J = 7.2 Hz, 3 H). 13C NMR (75 MHz,
CD3OD): δ = 176.1, 171.6, 138.1, 129.4, 129.0, 128.9,
111.4, 67.7, 51.9, 41.8, 18.3. HRMS (DART): m/z [M + H]+
calcd for C13H17N2O4S: 297.0904; found: 297.0891.
(S)-2-[2-{[(Benzyloxy)carbonyl]amino}-3-methylbutan-
amido]ethanethioic S-Acid (Cbz-L-Val-Gly-SH, 4b;
Table 3, Entry 2): white microcrystals (yield: 73%); mp
159–161 °C; [α]20D –25.2 (c = 0.5 in MeOH). 1H NMR (300
MHz, CDCl3): δ = 7.27–7.45 (m, 5 H), 6.80–6.90 (m, 1 H),
5.35–5.50 (m, 1 H), 5.05–5.16 (m, 2 H), 4.11–4.24 (m, 2 H),
4.04–4.10 (m, 1 H), 2.11–2.25 (m, 1 H), 0.99 (d, J = 6.8 Hz,
3 H), 0.95 (d, J = 6.8 Hz, 3 H). 13C NMR (75 MHz, CDCl3):
δ = 195.1, 172.0, 156.8, 136.2, 128.7, 128.4, 128.2, 67.4,
60.5, 50.4, 30.8, 19.5, 17.9. HRMS (ESI–): m/z [M – H]–
calcd for C15H19N2O4S: 323.1086; found: 323.1071.
(S)-2-[(S)-2-{[(Benzyloxy)carbonyl]amino}propan-
amido]-3-phenylpropanethioic S-Acid (Cbz-L-Ala-L-
Phe-SH, 4c; Table 3, Entry 3): white microcrystals (yield:
79%); mp 107–109 °C; [α]20D –17.9 (c = 0.14 in MeOH).
1H NMR (300 MHz, CDCl3): δ = 7.20–7.41 (m, 10 H), 7.10–
7.19 (m, 2 H), 6.42–6.61 (m, 1 H), 5.04–5.18 (m, 2 H), 4.81–
4.93 (m, 1 H), 4.10–4.27 (m, 1 H), 3.12–3.24 (m, 1 H), 2.97–
3.17 (m, 1 H), 1.31 (d, J = 7.1 Hz, 3 H). HRMS (ESI–): m/z
[M – H]– calcd for C20H21N2O4S: 385.1228; found:
385.1247.
(5S,8S)-8-Benzyl-5-methyl-3,6,9-trioxo-1-phenyl-2-oxa-
4,7,10-triazadodecane-12-thioic S-Acid (Cbz-L-Ala-L-
Phe-Gly-SH, 4d; Table 3. Entry 4): white microcrystals
(yield: 69%); mp 162–163 °C; [α]20D –31.4 (c = 0.5 in
MeOH). 1H NMR (300 MHz, CD3OD): δ = 7.13–7.42 (m, 10
H), 5.00–5.14 (m, 5 H), 4.61–4.70 (m, 1 H), 4.00–4.13 (m, 3
H), 3.17–3.29 (m, 1 H), 2.91–3.03 (m, 1 H), 1.21 (d, J = 7.2
Hz, 3 H). 13C NMR (75 MHz, CD3OD): δ = 175.5, 173.7,
138.4, 138.0, 130.3, 129.5, 129.4, 129.0, 128.9, 127.7, 67.9,
55.8, 52.3, 51.4, 49.0, 38.3, 17.9. HRMS (ESI–): m/z [M –
H]– calcd for C22H24N3O5S: 442.1442; found: 442.1455.
Synlett 2014, 25, 247–250
© Georg Thieme Verlag Stuttgart · New York