Dipodal Steroid Scaffold for Combinatorial Chemistry
FULL PAPER
Rf = 0.66 (pentane/EtOAc, 1:1 + 1% HOAc; PMA). 1H NMR
(500 MHz, CDCl3): δ = 5.87–5.97 (m, 1 H, Alloc), 5.30 (dd, 1.3 Hz;
17.2 Hz, 1 H, Alloc), 5.20 (br. d, 10.3 Hz, 1 H, Alloc), 4.78 (br. s,
1 H, NH), 4.60 (br. s, 1 H, NH), 4.55 (br. s, 2 H, Alloc), 3.92 (br.
s, 1 H, 12 βH), 3.48 (br. s, 1 H, 3 βH), 2.34–2.45 (m, 1 H), 2.18–
2.29 (m, 1 H), 0.97–1.92 (series of m, 34 H), 1.44 (s, 9 H, Boc CH3),
0.91 (s, 3 H), 0.90 (d, 6.4 Hz, 3 H, 21-CH3), 0.78 (s, 3 H). 13C NMR
(125 MHz, CDCl3): δ = 178.3 (COOH), 155.4 (Alloc C=O), 155.0
(Boc C=O), 132.9 (Alloc CH=CH2), 117.4 (Alloc CH=CH2), 79.0
(Boc C), 65.2 (Alloc O–CH2), 53.3 (CH), 50.9 (CH), 50.6 (CH),
48.4 (CH), 44.6 (C), 42.1 (CH), 35.8 (CH), 35.5 (CH2), 34.8 (CH),
34.5 (CH), 33.9 (C), 33.8 (CH2), 30.8 (CH2), 30.5 (CH2), 29.6
(CH2), 28.4 (Boc 3 x CH3), 27.3 (CH2), 26.7 (CH2), 26.4 (CH2),
26.0 (CH2), 23.6 (CH2), 23.3 (19-CH3), 17.0 (21-CH3), 13.7 (18-
Savage, Org. Lett. 2000, 2, 3015–3018; e) A. Madder, L. Li, H.
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[8] A. Madder et al., unpublished results.
[9] V. del Amo, L. Siracusa, T. Markidis, B. Baragaña, K. M.
Bhattarai, M. Galobardes, G. Naredo, M. N. Pérez-Payán,
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[10] Y. A. Cheng, T. Suenaga, W. C. Still, J. Am. Chem. Soc. 1996,
118, 1813–1814.
[11] a) H. Hsieh, J. G. Muller, C. J. Burrows, Bioorg. Med. Chem.
1995, 3, 823–838; b) For similar simultaneous, stereoselective
reductions see ref.[1c,5b,5g,9]
[12] 3,12-dioxo-5β-cholan-24-oic acid is also commercially available
from Steraloids, Inc. (Newport, Rhode Island, USA).
[13] After quenching the reduction mixture with a 12 HCl aque-
ous solution, solvents were evaporated under reduced pressure.
The crude residue (2.6 g) was dissolved in MeOH (30 mL),
Amberlyst 15 (wet) acidic ion-exchange resin (1.5 g) was added
and the mixture was shaken for 1 h. The resin was filtered and
washed with water and MeOH. After concentration under re-
duced pressure, the filtrate was treated similarly with a new
batch of Amberlyst resin. Both batches of resin were suspended
in a 7 NH3 solution in MeOH (30 mL) and the mixture was
gently shaken for 45 min. Upon filtration and washing with
MeOH, concentration of the filtrates under reduced pressure
and drying under high vacuum yielded about 88 mg of diamino
carboxylic acid 7 as an off-white solid. ES-MS (250 °C) m/z (%
rel. int.) 391.4 (100) [M + H]+, 782.4 (15) [2M + H]+.
[14] G. Sennyey, G. Barcelo, J. Senet, Tetrahedron Lett. 1987, 28,
5809–5810.
CH ). IR (neat): ν
= 3333 (m, br), 1708 (s) cm–1. ES-MS m/z
max
˜
3
(% rel. int.) 475.4 (42) [M – Boc]+, 597.4 (100) [M + Na]+, 1172.4
(43) [2M + Na]+. HR-MS (ES) m/z calcd. for C33H54N2O6 + H
575.4055, found 575.4058.
Supporting Information (see also the footnote on the first page of
this article): Integrated analytical approach for the determination
of the diastereomeric purity and identity of 5a and 6a and copies
1
of 13C (APT) and H NMR spectra.
Acknowledgments
This work was financially supported by Ghent University (BOF
011D16403) and the FWO Vlaanderen (KAN 1.5.186.03;
G.0347.04N). We gratefully thank A. P. Davis and C. J. Burrows
for useful discussions. We thank Jan Goeman for technical support
and assisting in the LC-MS experiments.
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[16] Savage and co-workers immobilize the C24 alcohol on an acid
chloride polystyrene resin (see ref.[5d]).
[17] Literature suggests sodium reduction at the C12 position is
nearly stereoselective (see ref.[5a,5d]). Other simultaneous re-
duction protocols of oximes (see ref.[11b]) give lower yields and/
or are again mainly hampered by formation of isomers at the
C3 position.
[18] Presumably chromatographic elimination of the minor dia-
stereomer is easier in case of the more polar diamino alcohol
compared to a diamino ester.
[19] H. W. Gao, J. R. Dias, Org. Prep. Proced. Int. 1999, 31, 145–
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[20] See supporting information for an integrated analytical ap-
proach for the determination of the diastereomeric purity and
identity of compounds 5a and 6a.
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Received: November 7, 2006
Published Online: February 20, 2007
Eur. J. Org. Chem. 2007, 1793–1797
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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