A. Arizpe, F. J. Sayago, A. I. Jiménez, M. Ordóñez, C. Cativiela
OMe), 29.68 (C-3), 27.81 (tBu CH3) ppm. 31P NMR (162 MHz, hexane CH2) ppm. 31P NMR (162 MHz, CDCl3): δ = 31.05 ppm.
FULL PAPER
[D6]DMSO):
δ
=
25.82 ppm. HRMS (ESI): calcd. for HRMS (ESI): calcd. for C10H21NO3P [M + H]+ 234.1254; found
C15H22NNaO5P [M + Na]+ 350.1128; found 350.1123.
234.1253.
Dimethyl (2R*,3aS*,7aS*)-N-(tert-Butoxycarbonyl)octahydroind-
ole-2-phosphonate (14): A mixture of 13 (206 mg, 0.63 mmol) and
PtO2 (21 mg) in acetic acid (10 mL) was heated at 45 °C under an
atmospheric pressure of hydrogen for 12 h. Filtration of the catalyst
and evaporation of the solvent afforded 14 as a white solid (209 mg,
Acknowledgments
The authors thank the Ministerio de Ciencia e Innovación (project
CTQ2010-17436), the Consejo Superior de Investigaciones Científ-
icas (project 2008MX0044; JAE predoctoral fellowship to A. A.),
the Gobierno de Aragón (group E40) and the Consejo Nacional de
Ciencia y Tecnología (CONACYT-MEXICO; projects 62271 and
J000.400/2009) for financial support.
0.63 mmol, 100% yield); m.p. 72–74 °C. IR (KBr): ν = 1693, 1230,
˜
1
1034 cm–1. H NMR (400 MHz, [D6]DMSO): δ = 4.08–4.01 (m, 1
H, 2-H), 3.81–3.74 (m, 1 H, 7a-H), 3.65 (d, J = 10.5 Hz, 3 H,
OMe), 3.64 (d, J = 10.5 Hz, 3 H, OMe), 2.20–1.98 (m, 3 H, 3-H,
3a-H), 1.72–1.53 (m, 4 H, cyclohexane CH2), 1.49–1.34 (m, 2 H,
cyclohexane CH2) overlapped with 1.40 (s, 9 H, tBu), 1.28–1.02 (m,
2
H, cyclohexane CH2) ppm. 13C NMR (100 MHz, [D6]-
DMSO): δ = 153.81 (COO), 78.94 (tBu C), 58.35 (C-7a), 52.92 (d,
J = 6.6 Hz, OMe), 52.18 (d, J = 5.7 Hz, OMe), 52.00 (d, J =
163.9 Hz, C-2), 35.87 (d, J = 5.9 Hz, C-3a), 29.00 (C-3), 27.96 (tBu
CH3), 27.32 (cyclohexane CH2), 25.19 (cyclohexane CH2), 23.55
(cyclohexane CH2), 19.85 (cyclohexane CH2) ppm. 31P NMR
(162 MHz, CDCl3): δ = 29.04 ppm. HRMS (ESI): calcd. for
C15H28NNaO5P [M + Na]+ 356.1597; found 356.1599.
[1] V. P. Kukhar, H. R. Hudson (Eds.), Aminophosphonic and Ami-
nophosphinic Acids: Chemistry and Biological Activity, Wiley,
Chichester, 2000.
[2] For recent reviews, see: a) F. Orsini, G. Sello, M. Sisti, Curr.
Med. Chem. 2010, 17, 264–289; b) E. D. Naydenova, P. T. To-
dorov, K. D. Troev, Amino Acids 2010, 38, 23–30; c) B. Lejczak,
P. Kafarski, Top. Heterocycl. Chem. 2009, 20, 31–63.
[3] For recent reviews, see: a) M. Ordóñez, H. Rojas-Cabrera, C.
Cativiela, Tetrahedron 2009, 65, 17–49; b) K. Moonen, I. Laur-
eyn, C. V. Stevens, Chem. Rev. 2004, 104, 6177–6215.
[4] For a review, see: M. Ordóñez, J. L. Viveros-Ceballos, C. Cativ-
iela, A. Arizpe, Curr. Org. Synth., in press.
(2R*,3aS*,7aS*)-Octahydroindole-2-phosphonic Acid Hydrobro-
mide (15): A 33% solution of hydrogen bromide in acetic acid
(2 mL) was added to 14 (50 mg, 0.15 mmol) and the reaction mix-
ture was stirred at room temperature for 2 h. The solvent was evap-
orated and the residue was taken up in water and lyophilised to
afford 15 as a white solid (43 mg, 0.15 mmol, 100% yield); m.p.
[5] F. J. Sayago, P. Laborda, M. I. Calaza, A. I. Jiménez, C. Cativi-
ela, Eur. J. Org. Chem. 2011, 2011–2028, and references cited
therein.
138–140 °C (dec.). IR (KBr): ν = 3413, 1179, 1024 cm–1. 1H NMR
˜
[6] For some medicinally useful compounds containing l-Oic, see:
a) J. Lawandi, S. Gerber-Lemaire, L. Juillerat-Jeanneret, N.
Moitessier, J. Med. Chem. 2010, 53, 3423–3438; b) K. Ersmark,
J. R. Del Valle, S. Hanessian, Angew. Chem. Int. Ed. 2008, 47,
1202–1223; c) R. P. Hicks, J. B. Bhonsle, D. Venugopal, B. W.
Koser, A. J. Magill, J. Med. Chem. 2007, 50, 3026–3036; d)
J. M. Stewart, L. Gera, D. C. Chan, E. J. York, V. Simkeviciene,
P. A. Bunn Jr., L. Taraseviciene-Stewart, Peptides 2005, 26,
1288–1291; e) J. M. Stewart, Peptides 2004, 25, 527–532; f) S.
Reissmann, D. Imhof, Curr. Med. Chem. 2004, 11, 2823–2844;
g) M. Hurst, B. Jarvis, Drugs 2001, 61, 867–896; h) B. Portevin,
M. Lonchampt, E. Canet, G. De Nanteuil, J. Med. Chem.
1997, 40, 1906–1918; i) P. A. Todd, A. Fitton, Drugs 1991, 42,
90–114.
[7] For reviews, see: a) S. K. Panday, J. Prasad, D. K. Dikshit, Tet-
rahedron: Asymmetry 2009, 20, 1581–1632; b) C. Nájera, M.
Yus, Tetrahedron: Asymmetry 1999, 10, 2245–2303.
[8] T. Shono, Y. Matsumura, K. Tsubata, Tetrahedron Lett. 1981,
22, 3249–3252.
[9] F. J. Sayago, A. I. Jiménez, C. Cativiela, Tetrahedron: Asym-
metry 2007, 18, 2358–2364.
[10] a) R. N. Kankan, D. R. Rao, PCT Int. Appl. WO 2005100317,
2005; Chem. Abstr. 2005, 143, 367597; b) M. Vincent, B.
Marchand, G. Rémond, S. Jaguelin-Guinamant, G. Damien,
B. Portevin, J.-Y. Baumal, J.-P. Volland, J.-P. Bouchet, P.-H.
Lambert, B. Serkiz, W. Luitjen, M. Laubie, P. Schiavi, Drug
Des. Discovery 1992, 9, 11–28; c) C. Pascard, J. Guilhem, M.
Vincent, G. Rémond, B. Portevin, M. Laubie, J. Med. Chem.
1991, 34, 663–669; d) M. Vincent, J. Baliarda, B. Marchand,
G. Remond, U.S. Patent 4914214, 1990; Chem. Abstr. 1989,
111, 115749.
[11] F. Fini, G. Micheletti, L. Bernardi, D. Pettersen, M. Fochi, A.
Ricci, Chem. Commun. 2008, 4345–4347.
[12] F. J. Sayago, M. J. Pueyo, M. I. Calaza, A. I. Jiménez, C. Cativ-
iela, Chirality 2011, DOI: 10.1002/chir.20952.
(400 MHz, [D6]DMSO): δ = 9.62 (br. s, 1 H, NH), 8.68 (br. s, 1 H,
NH), 4.68 (br. s, 2 H, OH), 3.61–3.48 (m, 2 H, 2-H, 7a-H), 2.32–
2.22 (m, 1 H, 3a-H), 2.14–2.03 (m, 1 H, 3-H), 2.02–1.91 (m, 1 H,
3-HЈ), 1.84–1.74 (m, 1 H, cyclohexane CH2), 1.72–1.46 (m, 4 H,
cyclohexane CH2), 1.41–1.16 (m, 3 H, cyclohexane CH2) ppm. 13C
NMR (100 MHz, [D6]DMSO): δ = 58.62 (C-7a), 53.07 (d, J =
147.8 Hz, C-2), 36.56 (d, J = 8.2 Hz, C-3a), 28.73 (C-3), 24.70 (cy-
clohexane CH2), 24.25 (cyclohexane CH2), 22.05 (cyclohexane
CH2), 20.22 (cyclohexane CH2) ppm. 31P NMR (162 MHz, [D6]-
DMSO): δ = 14.66 ppm. HRMS (ESI): calcd. for C8H17NO3P [M –
Br]+ 206.0941; found 206.0936.
Dimethyl (2R*,3aS*,7aS*)-Octahydroindole-2-phosphonate (16):
An ice-cooled solution of 14 (64 mg, 0.19 mmol) in dichlorometh-
ane (3.8 mL) was treated with trifluoroacetic acid (219 mg,
0.15 mL, 1.92 mmol) and stirred at room temperature for 12 h. The
reaction mixture was diluted with dichloromethane (15 mL) and a
saturated aqueous solution of NaHCO3 (8 mL) was added. The
layers were separated and the aqueous phase was further extracted
with dichloromethane (15 mL). The combined organic layers were
washed with brine (10 mL), dried and filtered. Evaporation of the
solvent provided 16 as a white solid (42 mg, 0.18 mmol, 93% yield);
m.p. 123–125 °C (dec.). IR (KBr): ν = 3391, 1230, 1198, 1041 cm–1.
˜
1H NMR (400 MHz, CDCl3): δ = 3.79 (d, J = 10.3 Hz, 3 H, OMe),
3.77 (d, J = 10.4 Hz, 3 H, OMe), 3.41 (ddd, J = 9.2, 8.4, 5.7 Hz, 1
H, 2-H), 3.08–3.03 (m, 1 H, 7a-H), 2.24 (br. s, 1 H, NH), 2.07–197
(m, 2 H, 3-H, 3a-H), 1.83–1.71 (m, 1 H, 3-HЈ), 1.68–1.55 (m, 2 H,
cyclohexane CH2), 1.53–1.42 (m, 4 H, cyclohexane CH2), 1.34–1.17
(m, 2 H, cyclohexane CH2) ppm. 13C NMR (100 MHz, CDCl3): δ
= 58.60 (d, J = 13.1 Hz, C-7a), 52.67 (d, J = 164.5 Hz, C-2), 53.41
(d, J = 6.8 Hz, OMe), 52.98 (d, J = 7.2 Hz, OMe), 38.26 (d, J =
7.7 Hz, C-3a), 32.05 (d, J = 1.9 Hz, 3-C), 28.70 (cyclohexane CH2),
27.77 (cyclohexane CH2), 23.68 (cyclohexane CH2), 21.91 (cyclo-
[13] M. Porcs-Makkay, G. Argay, A. Kálmán, G. Simig, Tetrahe-
dron 2000, 56, 5893–5903.
3080
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Eur. J. Org. Chem. 2011, 3074–3081