Synthesis of new derivatives of 11-thiolupinine

Article abstract of DOI:10.1080/17415993.2010.531481

A set of 11-thiofunctionalized derivatives of natural (-)-lupinine have been synthesized using phosphine-based redox type methods such as Hata and Mitsunobu reactions.

Full text of DOI:10.1080/17415993.2010.531481

Journal of Sulfur Chemistry
Vol. 31, No. 6, December 2010, 493–498
Synthesis of new derivatives of 11-thiolupinine
David Gueyrarda*, Rustam T. Tlegenovb, Siegfried Steinbrucknerc, Bruno Perlyc and Patrick
Rollind
aUniversité Claude Bernard Lyon 1, Laboratoire Chimie Organique II-Glycochimie–ICBMS, UMR 5246,
43 Bd du 11 novembre 1918, F-69622 Villeurbanne, France; bKarakalpakstan State University, 1 akad.
Abdirova, 742012 Nukus, Karakalpak Republic, Uzbekistan; cDRECAM-SCM, CEA Saclay, F-91191 Gif-
sur-Yvette, France; dICOA-UMR 6005, Université d’Orléans, BP 6759, F-45067 Orléans Cedex 2, France
(Received 5 August 2010; final version received 10 October 2010)
A set of 11-thiofunctionalized derivatives of natural (−)-lupinine have been synthesized using phosphine-
based redox type methods such as Hata and Mitsunobu reactions.
Keywords: thioalkaloids; thiolupinine; thiofunctionalization; Hata reaction; Mitsunobu reaction
1. Introduction
Sulfur-containing alkaloidic structures constitute an important niche as a remarkable sub-class
among alkaloids, usually exhibiting interesting biological properties (1). The most frequently
reported activities for thioalkaloids involve, in particular, cytotoxicity, antifungal, antiviral
and immunosuppressive activity (2). Some thioalkaloids found in Nuphar species can act as
antimicrobial and antiherbivore compounds (3).
In alkaloids, the simple quinolizidinic frame is mainly encountered within a few vegetable gen-
era (Lupinus, Thermopsis, Anabasis, etc.) in which (−)-lupinine (1) and its derivatives constitute
a major class of biologically relevant compounds (4, 5).
Some sulfur-containing lupinine analogs have been synthesized in the frame of a pharmaco-
modulation approach by Sparatore et al. (6), with a view to building up new ligands for
diverse receptors. All those thiolupinine-derived sulfides were generally prepared by reacting
11-thiolupinine (2) (7) with diverse electrophilic partners. The strongly oxidizable character of
primary thiol 2 makes it a very inconvenient reagent to access thio-functionalized derivatives of
lupinine in good conditions. Therefore, taking advantage of previous findings (8) related to direct
conversion of alcohols into miscellaneous hetero-functionalized derivatives using PPh3-based
redox methods (9, 10), we explored the introduction of a thiofunction on natural (−)-lupinine
(1). This quinolizidine alkaloid can be obtained in enantiomerically pure form either from several
Lupinus species (Leguminosae) or Anabasis aphylla L. (Chenopodiaceae) (5). With a view to
*Corresponding author. Email: david.gueyrard@univ-lyon1.fr
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2010 Taylor & Francis
DOI: 10.1080/17415993.2010.531481
http://www.informaworld.com

494 D. Gueyrard et al.
Table 1. Comparison of 1H and 13C NMR data of lupinine (1) and thiolupinine (2).
H
10
2
1
9
8
3
N
6
4
7
11
X
X = OH lupinine (1)
SH thiolupinine (2)
δHn (ppm)
δCn (ppm)
n
1
2
1
2
1
2
3
4
6
7
8
9
10
11
1.41
1.82
38.1
30.4
22.3
56.7
56.7
25.1
24.3
29.2
64.7
64.7
38.1
27.6
20.6
57.2
57.2
25.4
24.7
29.7
65.3
37.1
1.40, 1.73
1.38, 1.97
1.70, 2.68
1.70, 2.68
1.42
1.12, 1.64
1.34, 1.58
1.97
1.36, 1.96
1.41, 1.68
1.91, 2.79
1.91, 2.79
1.48, 1.54
1.22, 1.73
1.38, 1.44
1.96
3.56, 3.95
2.78, 2.97
Figure 1. 13C NMR spectra of lupinine (1) and thiolupinine (2).
explore the bioactivity modulation of this alkaloid through heterofunctional modifications, we
here report the introduction of miscellaneous sulfur-centered functions in place of the hydroxyl
group of lupinine.
In a first attempt to introduce a sulfur function on the primary position, we produced 11-
thiolupinine (2) from (−)-lupinine using Sparatore’s three-step sequence (7). Full assignment of
11-thiolupinine (2) was performed using an adapted set of dedicated NMR experiments, and 1H
and 13C data of lupinine and thiolupinine were compared (Table 1, Figure 1).
Conversion of 1 into the phenylsulfanyl derivative 3 was readily effected by reacting the primary
alcohol with diphenyl disulfide and tri-n-butylphosphine under Hata’s conditions (Scheme 1)
(10, 11).

Journal of Sulfur Chemistry 495
OH
SPh
H
N
H
N
PhSSPh
Bu3P, pyridine
82%
3
Scheme 1. Direct conversion of 1 into the phenylsulfanyl derivative.
However, in connection with methodological studies previously developed in the laboratory
(8b, 8d, 12), the Mitsunobu reaction appeared as an optimal tool to synthesize aza-heterocyclic
hybrid compounds based on the lupinine frame. A range of heteroarylsulfanyl derivatives were
thus obtained in 70–90% yields using a single-step Mitsunobu approach involving commercially
available and easy-to-handle heteroaryl mercaptans (Scheme 2).
OH
SHet
H
N
H
N
Het: 2-pyridyl
8-quinolinyl
4
5
6
7
73%
70%
82%
90%
HetSH, PPh3
2-benzothiazolyl
2-benzoxazolyl
DIAD, pyridine
Scheme 2. Single-step synthesis from lupinine of aza-heterocyclic hybrid compounds.
Likewise, a similar methodology allowed transformation of lupinine into thioesters: 11-
thiolupinine S-benzoate (8) was prepared from thiobenzoic acid in 75% yield (13), whereas
the corresponding S-xanthate (9) and S-dithiocarbamate (10) were obtained in ca. 60% yield by
using inexpensive potassium O-ethylxanthate and ziram (Scheme 3) (14).
PhCOSH
or
OH
SR
EtOCSSK
or
Zn(SCSNMe2)2
H
N
H
N
R = PhCO
EtOCS
8
9
75%
62%
10 60%
Me2NCS
PPh ,
DIAD
3
pyridine
Scheme 3. Single-step synthesis of thioesters derived from lupinine.
In conclusion, we have introduced a convenient one-pot procedure to convert natural (−)-
lupinine into diverse sulfur-functionalized derivatives, including aryl and heteroaryl sulfides and
thioesters, by using phosphine-based redox-type methods such as Hata and Mitsunobu reactions.
Current efforts focus on broadening the scope of the method and evaluate the biological activity
of such thioalkaloidic compounds.
2. Experimental
2.1. General
Anhydrous reactions were performed in pre-dried flasks, using anhydrous solvents (which were
distilled when necessary according to D.D. Perrin, W.L.F. Armarego and D.R. Perrin, Purification

496 D. Gueyrard et al.
of Laboratory Chemicals; Pergamon: Oxford, 1986) and under argon atmosphere. (−)-Lupinine
was extracted from A. aphylla (15), and a sample of 11-thiolupinine was synthesized accord-
ing to Novelli and Sparatore (7). All other chemicals obtained from commercial suppliers were
used without further purification. TLC using pre-coated aluminum-back plates (Merck Kiesel-
gel 60F254) were visualized by ultraviolet light (254 nm) and by charring after exposure to
a 5% H2SO4 solution in ethanol. Flash column chromatography was performed using silica
gel (36–63 mesh, E. Merck). Melting points (◦C) were determined with a Köfler hot-stage
apparatus and are uncorrected. Optical rotations were measured at 20 ◦C with a Perkin-Elmer
1
141 polarimeter. NMR spectra were recorded on a Bruker AMX 500 (500 MHz for H and
125.7 MHz for 13C) spectrometer. Chemical shifts are expressed in parts per million (ppm) down-
1
field from TMS. Coupling patterns for H NMR are designated as s = singlet, d = doublet,
t = triplet, q = quartet, m = multiplet, and coupling constants are given in Hertz (Hz). NMR
peak assignments have been established using NOESY, COSY, HSQC and HMBC methods on
®
all reported compounds. Mass spectra were recorded on an API-300 spectrometer [Ionspray
(IS) or heated nebulizer (HN) ionization mode]. HRMS were measured on a MicrOTOF-QII
(ESI mode).
2.2. 11-Phenylsulfanyllupinane (3)
A solution of (−)-lupinine (0.2 g, 1.18 mmol), diphenyl disulfide (515 mg, 2 equiv.) and tri-n-
butylphosphine (0.6 ml, 2 equiv.) in pyridine (4 ml) was stirred at 80◦C for 24 h. The solvent
was evaporated under reduced pressure, and then co-evaporation with toluene was effected.
Chromatographic purification (eluent EtOAc/MeOH/H2O, 95:4:1) of the residue provided the
11-phenylsulfanyllupinane (3; 253 mg, 82% yield) as a yellow syrup, [α]D−23 (ca. 1.0, CHCl3)
(6c). 1H NMR (CDCl3) δ 1.70–1.80 (m, 2H, H-3eq, H-8eq), 1.95–2.10 (m, 5H), 2.86 (m,
2H, H-4eq, H-6eq), 3.07 (dd, 1H, Jgem = 12.7, Jvic = 4.2, H-11b), 3.24 (dd, 1H, Jgem = 12.7,
Jvic = 10.0, H-11a), 7.14 (brt, 1H, Jvic = 7.0, para-H-Ar), 7.25 (brt, 2H, Jvic = 7.2, meta-H-
Ar), 7.32 (brd, 2H, Jvic = 7.5, ortho-H-Ar). 13C NMR δ 20.3 (C-3), 24.7 (C-8), 25.3 (C-7), 27.8
(C-2), 29.6 (C-9), 32.1 (C-11), 37.9 (C-1), 57.2 (C-4, C-6), 65.2 (C-10), 125.4 (para-C-Ar),
128.6 (C-Ar), 137.2 (ipso-C-Ar). ESI-HRMS Calcd for C16H24NS: 262.1629. Found: 262.1612
[M+H]+.
2.3. General procedure for the Mitsunobu conversion of (−)-lupinine into
11-thiofunctionalized derivatives (4–10)
To a stirred solution of (−)-lupinine (0.2 g, 1.18 mmol), the thio-nucleophile (1.1–1.5 equiv.) and
triphenylphosphine (0.37 g, 1.2 equiv.) in pyridine (4 ml), diisopropylazodicarboxylate (0.28 ml,
1.2 equiv.) was added dropwise at 0◦C, then stirring was continued at rt until complete con-
sumption of the alcohol (TLC). The solvent was evaporated under reduced pressure, then
co-evaporation with toluene was effected. Chromatographic purification of the residue provided
the 11-thiofunctionalized derivatives.
2.4. 11-(2-Pyridylsulfanyl)lupinane (4)
Compound 4 was isolated (after 30 min stirring; eluent CH2Cl2/MeOH, 19:1) in 73% yield as a
yellow syrup. [α]D−7 (ca. 1.0, CHCl3). 1H NMR (CDCl3) δ 2.97 (m, 2H, H-4eq, H-6eq), 3.23 (dd,
1H, Jgem = 13.3, Jvic = 9.7, H-11b), 3.53 (brdd, 1H, Jvic = 4.0, H-11a), 6.94 (dd, 1H, J5,6 = 4.9,
J4,5 = 7.7, H-5Pyr), 7.16 (brd, 1H, J3,4 = 7.9, H-3Pyr), 7.45 (brt, 1H, J4,5 = 7.7, H-4Pyr), 8.38
(brd, 1H, J5,6 = 4.9, H-6Pyr). 13C NMR δ 20.6 (C-3), 24.2 (C-7, C-8), 27.2 (C-11), 28.8 (C-2), 29.6

Journal of Sulfur Chemistry 497
(C-9), 37.9 (C-1), 56.8 (C-4, C-6), 65.1 (C-10), 119.1 (C-5Pyr), 122.0 (C-3Pyr), 135.7 (C-4Pyr),
149.3 (C-6Pyr), 158.5 (C-2Pyr). ESI-HRMS Calcd for C15H23N2S: 263.1582. Found: 263.1573
[M+H]+.
2.5. 11-(8-Quinolinylsulfanyl)lupinane (5)
Compound 5 was isolated (after 30 min stirring; eluent CH2Cl2/MeOH, 19:1) in 70% yield as a
crystalline white solid, m.p. 110◦C (m.p. 111–112◦C) (16), [α]D−19 (ca. 1.0, CHCl3). 1H NMR
(CDCl3) δ 2.57 (m, 2H, H-4eq, H-6eq), 2.93 (dd, 1H, Jgem = 12.6, Jvic = 4.3, H-11b), 3.06 (brdd,
1H, Jgem = 12.6, Jvic = 10.1, H-11a), 7.09 (dd, 1H, J3,4 = 8.2, J2,3 = 4.2, H-3Qui), 7.16 (dd, 1H,
J5,6=8.2, J6,7=7.3, H-6Qui), 7.22 (brd, 1H, J5,6 = 8.2, H-5Qui), 7.25 (brd, 1H, J6,7 = 7.3, H-7Qui),
7.78 (dd, 1H, J3,4 = 8.2, J2,4 = 1.8, H-4Qui), 8.66 (dd, 1H, J2,4 = 1.8, J2,3 = 4.2, H-2Qui). 13
C
NMR δ 20.2 (C-3), 24.2 (C-8), 24.9 (C-7), 28.2 (C-2), 28.9 (C-11), 29.3 (C-9), 36.9 (C-1), 56.4 (C-
6), 56.7 (C-4), 64.9 (C-10), 120.9 (C-3Qui), 122.8 (C-5Qui), 123.1 (C-7Qui), 125.9 (C-6Qui), 127.5
(C-4aQui), 135.7 (C-4Qui), 138.9 (C-8Qui), 144.7 (C-8aQui), 148.4 (C-2Qui). ESI-HRMS Calcd for
C19H25N2S: 313.1738. Found: 313.1727 [M+H]+.
2.6. 11-(Benzothiazol-2-ylsulfanyl)lupinane (6)
Compound 6 was isolated (after 30 min stirring; eluent CH2Cl2/MeOH, 19:1) in 82% yield
1
as a yellow syrup. [α]D−28 (ca. 1.0, CHCl3). H NMR (CDCl3) δ 1.80–1.90 (m, 2H, H-
3eq, H-8eq), 1.95–2.10 (m, 4H, H-1, H-2eq, H-4ax, H-6ax), 2.12 (brs, 1H, H-10), 2.88 (m,
2H, H-4eq, H-6eq), 3.42 (dd, 1H, Jgem = 13.2, Jvic = 9.6, H-11b), 3.72 (dd, 1H, Jgem = 13.2,
Jvic = 4.2, H-11a), 7.27 (brt, 1H, Jvic = 8.0, H-6Btz), 7.39 (brt, 1H, Jvic = 8.1, H-5Btz), 7.73
(brd, 1H, Jvic = 8.0, H-7Btz), 7.84 (brd, 1H, Jvic = 8.1, H-4Btz). 13C NMR δ 20.5 (C-3), 24.6
(C-8), 25.1 (C-7), 27.9 (C-2), 29.4 (C-9), 33.4 (C-11), 38.1 (C-1), 56.6 (C-6), 57.1 (C-4),
65.3 (C-10), 120.8 (C-7Btz), 121.3 (C-4Btz), 123.9 (C-6Btz), 125.8 (C-5Btz), 135.0 (C-7aBtz),
153.2 (C-3aBtz), 167.5 (C-2Btz). ESI-HRMS Calcd for C17H23N2S2: 319.1303. Found: 319.1295
[M+H]+.
2.7. 11-(Benzoxazol-2-ylsulfanyl)lupinane (7)
Compound 7 was isolated (after 30 min stirring; eluent CH2Cl2/MeOH, 19:1 and then 9:1) in 90%
yield as a yellow syrup. [α]D−23 (ca. 1.0, CHCl3). 1H NMR (CDCl3) δ 1.80–1.90 (m, 2H, H-3eq,
H-8eq), 1.95–2.10 (m, 4H, H-1, H-2eq, H-4ax, H-6ax), 2.12 (brs, 1H, H-10), 2.87 (m, 2H, H-4eq, H-
6eq), 3.41 (dd, 1H, Jgem = 13.1, Jvic = 9.5, H-11b), 3.71 (dd, 1H, Jgem = 13.1, Jvic = 4.7, H-11a),
7.22 (brt, 1H,Jvic = 7.7, H-6Box), 7.27 (brt, 1H, Jvic = 7.4, H-5Box), 7.42 (brd, 1H, Jvic = 7.7,
H-7Box), 7.58 (brd, 1H, Jvic = 7.4, H-4Box). 13C NMR δ 20.4 (C-3), 24.7 (C-8), 25.1 (C-7), 28.0
(C-2), 29.6 (C-9), 31.2 (C-11), 38.1 (C-1), 56.6 (C-6), 57.0 (C-4), 65.2 (C-10), 109.5 (C-7Box),
118.0 (C-4Box), 123.5 (C-6Box), 124.0 (C-5Box), 142.5 (C-3aBox), 152.5 (C-7aBox), 165.0 (C-2Box).
ESI-HRMS Calcd for C17H23N2OS: 303.1531. Found: 303.1520 [M+H]+.
2.8. 11-Thiolupinine S-benzoate (8)
Compound 8 was isolated (after 3 h stirring; eluent EtOAc/MeOH/H2O, 90:8:2) in 75% yield as
a white solid, m.p. 98–100◦C, [α]D+3 (ca. 1.0, CHCl3). 1H NMR (CDCl3) δ 3.02 (m, 2H, H-4eq,
H-6eq), 3.18 (dd, 1H, Jgem = 13.5, Jvic = 9.7, H-11b), 3.48 (dd, 1H, Jgem = 13.5, Jvic = 4.0,
H-11a), 7.65 (m, 3H, H-Ar), 7.95 (m, 2H, H-Ar).13C NMR δ 20.6 (C-3), 24.8 (C-7, C-8), 27.8
(C-2), 29.5 (C-9), 31.0 (C-11), 37.7 (C-1), 56.9 (C-4, C-6), 65.2 (C-10), 126.5, 127.6 (CH-Ar),

498 D. Gueyrard et al.
=
128.5 (CIV-Ar), 133.3 (CH-para-Ar), 193.0 (C O). ESI-HRMS Calcd for C17H24NOS: 290.1579.
Found: 290.1573 [M+H]+.
2.9. 11-Thiolupinine S-ethylxanthate (9)
Compound 9 was isolated (after 3 h stirring; eluent EtOAc/MeOH/H2O, 95:4:1) in 62% yield as
a beige gum, [α]D−20 (ca. 1.0, CHCl3). 1H NMR (CDCl3) δ 1.42 (t, 3H, Jvic = 7.1, CH3), 2.87
(m, 2H, H-4eq, H-6eq), 3.21 (dd, 1H, Jgem = 13.6, Jvic = 9.6, H-11b), 3.53 (dd, 1H, Jgem = 13.6,
Jvic = 4.1, H-11a), 4.64 (q, 2H, Jvic = 7.1, OCH2).13C NMR δ 13.7 (CH3), 20.7 (C-3), 24.7
(C-8), 25.0 (C-7), 28.2 (C-2), 29.6 (C-9), 34.5 (C-11), 37.5 (C-1), 56.5, 57.0 (C-4, C-6), 65.0
=
(C-10), 69.7 (OCH2), 215.0 (C S). ESI-HRMS Calcd for C13H24NOS2: 274.1299. Found:
274.1286 [M+H]+.
2.10. 11-Thiolupinine S-(N,N-dimethyl)dithiocarbamate (10)
Compound 10 was isolated (after 3 h stirring; eluent EtOAc/MeOH/H2O, 90:8:2) in 60% yield
as a beige gum, [α]D−11 (ca. 1.0, CHCl3). 1H NMR (CDCl3) δ 2.96 (m, 2H, H-4eq, H-6eq), 3.36
and 3.53 (2s, Me2N), 3.40 (dd, 1H, Jgem = 13.8, Jvic = 9.5, H-11b), 3.76 (dd, 1H, Jgem = 13.8,
Jvic = 4.2, H-11a). 13C NMR δ 20.4 (C-3), 24.7 (C-8), 25.0 (C-7), 27.1 (C-2), 29.2 (C-9), 36.2
(C-1), 37.1 (C-11), 41.6 and 45.1 (Me2N), 57.0 (C-4, C-6), 65.4 (C-10), 197.5 (C=S). ESI-HRMS
Calcd for C13H25N2S2: 273.1459. Found: 273.1441 [M+H]+.
Acknowledgements
The authors thank Professor Dr Michael Wink (IPMB, Universität Heidelberg) for his helpful comments.
References
(1) Wrobel, J.T.; Wojtasiewicz, K. In The Alkaloids: Brossi, A., Ed.; Academic: New York, 1992; pp 249–297.
(2) (a) Matsuda, H.; Morikawa, T.; Oda, M.; Asao, Y.; Yoshikawa, M. Bioorg. Med. Chem. Lett. 2003, 13, 4445–4449;
(b) Wang, W.; Oda, T.; Fujita, A.; Mangindaan, R.E.P.; Nakazawa, T.; Ukai, K.; Kobayashi, H.; Namikoshi, M.
Tetrahedron 2007, 63, 409–412.
(3) LaLonde, R.T.; Wong, C. Pure Appl. Chem. 1977, 49, 169–182.
(4) Wink, M. Methods Plant Biochem. 1993, 8, 197–239.
(5) Michael, J.P. Nat. Prod. Rep. 2008, 25, 139–165.
(6) (a) Novelli, F.; Tasso, B.; Sparatore, F. Il Farmaco 1999, 54, 354–358; (b) Tasso, B.; Sparatore, A.; Sparatore, F. Il
Farmaco 2003, 58, 669–676; (c) Sparatore, A.; Novelli, F.; Sparatore, F. Helv. Chim. Acta 2004, 87, 580–591.
(7) Novelli, F.; Sparatore, F. Il Farmaco 1993, 48, 1021–1049.
(8) (a) Besson, T.; Al Neirabeyeh, M.; Viaud, M.C.; Rollin, P. Synth. Commun. 1990, 20, 1631–1639; (b) Viaud, M.C.;
Rollin, P. Synthesis 1990, 130–131; (c) Gueyrard, D.; Lorin, C.; Moravcova, J.; Rollin, P. J. Carbohydr. Chem. 1999,
18, 317–331; (d) Moravcova, J.; Spilova, L.; Capkova, J.; Chéry, F.; Rollin, P. Coll. Czech Chem. Commun. 2000,
65, 1745–1753.
(9) (a) Mitsunobu, O. Synthesis 1981, 1–28; (b) Hughes, D.L. Org. Reactions 1992, 42, 335–656.
(10) Nakagawa, I.; Aki, K.; Hata, T. J. Chem. Soc., Perkin Trans. 1 1983, 1315–1318.
(11) (a) Cleary, D.G. Synth. Commun. 1989, 19, 737–744; (b) Marot, C.; Philipp, C.; Rollin, P. Tetrahedron Lett. 1992,
33, 4575–4578; (c) Takano, S.; Sugihara, Y.; Ogasawara, K. Synlett 1992, 668–670; (d) Cassel, S.; Chaimbault, P.;
Lafosse, M.; Lorin, C.; Rollin, P. Sulfur Lett. 1996, 20, 63–70.
(12) (a) Dancy, I.; Laupichler, L.; Rollin, P.; Thiem, J. Synlett 1992, 283–284; (b) Dancy, I.; Laupichler, L.; Rollin, P.;
Thiem, J. Liebigs Ann. Chem. 1993, 343–350.
(13) see, for example, Skaddan, M.B.; Wüst, F.R.; Katzenellenbogen, J.A. J. Org. Chem. 1999, 64, 8108–8121.
(14) (a) Rollin, P. Tetrahedron Lett. 1986, 27, 4169–4170; (b) Aversa, M.C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.
J. Org. Chem. 1999, 64, 2114–2118.
(15) Zakharov, V.P.; Aslanov, Kh.A.; Sadykov, A.S.; Ishbaev, A.I. Uzb. Khim. Zh. 1975, 19, 60–64.
(16) Tlegenov, R.T.; Pakarinen, J.M.H.; Oresmaa, L.; Ahlgrén, M.; Vainiotalo, P. J. Heterocycl. Chem. 2007, 44, 1339–
1344.

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