COMMUNICATIONS
Adducts 7c ± e and 11c ± e: Hydrazone 1 or 5 was solved in excess (about
5 equiv) of ketone (6c ± e), and the mixture was stirred until consumption
of the former (TLC). Unchanged ketone was recovered (75 ± 85%) by
bulb-to-bulb distillation, and the residue was purified by flash chromatog-
raphy.
polarization effects. No absorption correction. The structure was
solved by Patterson and Fourier methods, and a final mixed refine-
ment was undertaken. Hydrogen atoms were located in a difference
synthesis, and their coordinates and isotropic thermal parameters
refined, except for H2 whose thermal parameter was fixed. Refine-
ment on F 2 for all reflections. Weighted factors (wR) and all GOFs are
based on F 2; conventional R factors are based on F. The configuration
of C(5) is based on that known for the auxiliary. Crystallographic data
(excluding structure factors) for the structure reported in this paper
have been deposited with the Cambridge Crystallographic Data
Center as supplementary publication no. CCDC-102999. Copies of the
data can be obtained free of charge on application to CCDC, 12 Union
Road, Cambridge CB21EZ, UK (fax: (44)1223-336-033; e-mail:
deposit@ccdc.cam.ac.uk).
Compounds 12 and 14 were synthesized from 11 under standard conditions.
Aldehydes 13: Ozone was bubbled through a solution of 12 (1 mmol) in dry
CH2Cl2 (5 mL) at 788C until appearance of a permanent blue color (5 ±
10 min). Me2S (5 mmol) was added. The mixture was allowed to warm to
room temperature and concentrated, and the residue purified by column
chromatography.
Carboxylic acids 15: Ozonolysis was carried out from 14 as described
above, but only 1 mmol of Me2S was added. To the resulting solution was
added tBuOH (12 mL) and isobutene (10 mL). After the mixture was
cooled to 08C, a solution of NaClO2 (10 mmol) and KH2PO4 (9 mmol) in
H2O (12 mL) was added dropwise and the mixture was stirred for 16 h. The
solvent was removed, and the residue was treated with 1m NaOH and
extracted with Et2O (2 Â 10 mL). The aqueous layer was acidified to pH 1
(HCl) and extracted with ethyl acetate (10 Â 5 mL). The combined organic
layers were then concentrated and purified by flash chromatography.
[10] D. J. Bailey, D. OꢁHagan, M. Tavasli, Tetrahedron: Asymmetry 1997, 8,
149 ± 153.
Ä
[11] D. Enders, H. Kipphardt, P. Gerdes, L. J. Brena-Valle, V. Buhshan,
Bull. Soc. Chim. Belg. 1988, 97, 691 ± 704.
Received: June 19, 1998 [Z12015IE]
Detection of Specific Noncovalent Zinc Finger
Peptide ± Oligodeoxynucleotide Complexes by
Matrix-Assisted Laser Desorption/Ionization
Mass Spectrometry**
German version: Angew. Chem. 1998, 110, 3598 ± 3600
Keywords: asymmetric synthesis
´
chiral auxiliaries
´
fluorine ´ hydrazones ´ nucleophilic additions
Edda Lehmann and Renato Zenobi*
[1] a) J. T. Welch, S. Eswarakrishnan, Fluorine in Bioorganic Chemistry,
Wiley, New York, 1991; b) Organofluorine Chemistry, Principles and
Commercial Applications (Eds.: R. E. Banks, B. E. Smart, J. C.
Tatlow), Plenum, New York, 1994.
All retroviruses, including the human immunodeficiency
virus type 1 (HIV-1), encode a gag precursor polyprotein
which contains zinc binding domains of the type CCHC
(CCHC Cys-X2-Cys-X4-His-X4-Cys, X variable amino
acid).[1] These zinc-coordinated motifs play an important role
in the recognition of viral ribonucleic acid and replication of
the virus. The interaction between peptides containing such
motifs and single-stranded nucleic acids has been extensively
studied,[2, 3] mainly in view of developing antiviral agents for
the treatment of the acquired immunodeficiency syndrome
(AIDS).[4] The methods used for these investigations are
rather time-consuming and expensive. Here we report that
matrix-assisted laser desorption/ionization mass spectrometry
(MALDI-MS) is suitable for detecting specific noncovalent
complexes, and that it is a potential method for rapidly
screening antiviral agents. The use of MALDI-MS is now well
known for the analysis of high molecular weight biopoly-
mers.[5] However, its ability to detect specific noncovalent
complexes is just starting to be explored.[6] Complexes that are
stable under physiological conditions in solution may not
survive laser desorption and ionization processes. Using
carefully designed controls, we were able to establish a
correlation between the existence of a specific noncovalent
triple complex in solution and in the MALDI mass spectra.
[2] a) T. Ido, K. Fukushi, T. Irie in Biomedicinal Aspects of Fluorine
Chemistry (Eds.: R. Filler, Y. Kobayashi), Kodansha, Tokio, and
Elsevier, Amsterdam, 1982; b) Organofluorine Compounds in Medic-
inal Chemistry and Biomedical Applications (Eds.: R. Filler, Y.
Kobayashi, L. M. Yagupolskii), Elsevier, Amsterdam, 1993.
[3] a) S. Arakawa, K. Nito, J. Seto, J. Mol. Cryst. Liq. 1991, 204, 15; b) R.
Buchecker, S. M. Kelly, J. Fünfschilling, Liq. Cryst. 1990, 8, 217;
c) T. R. Doyle, O. Vogol, J. Am. Chem. Soc. 1989, 111, 8510; d) Y.
Suzuki, T. Hagiwara, I. Kawamura, N. Okamura, T. Kitazume, M.
Kakimoto, Y. Imai, Y. Ouchi, H. Takezoe, A. Fukuda, Liq. Cryst. 1989,
6, 167.
[4] J. Wiedemann, T. Heiner, G. Mloston, G. K. Surya Prakash, G. Olah,
Angew. Chem. 1998, 110, 880 ± 881; Angew. Chem. Int. Ed. 1998, 37,
820 ± 821, and references therein.
[5] a) P. Bravo, M. Frigerio, G. Resnati, J. Org. Chem. 1990, 55, 4216 ±
Â
Â
4218; b) A. Dondoni, A. Boscarato, P. Formaglio, J.-P. Begue, F.
Benayoud, Synthesis 1995, 654 ± 658.
Â
[6] a) J. M. Lassaletta, R. Fernandez, Tetrahedron Lett. 1992, 33, 3691 ±
Â
3694; b) R. Fernandez, C. Gasch, J. M. Lassaletta, J. M. Llera,
Tetrahedron Lett. 1994, 35, 471 ± 472; c) D. Enders, R. Syrig, G. Raabe,
Â
R. Fernandez, C. Gasch, J. M. Lassaletta, J. M. Llera, Synthesis 1996,
Â
48 ± 52; d) J. M. Lassaletta, R. Fernandez, C. Gasch, J. Vazquez,
Tetrahedron 1996, 52, 9143 ± 9160.
Â
[7] J. M. Lassaletta, R. Fernandez, E. Martín-Zamora, E. Díez, J. Am.
Â
Chem. Soc. 1996, 118, 7002 ± 7003; b) E. Díez, F. Fernandez, C. Gasch,
Â
J. M. Lassaletta, J. M. Llera, E. Martín-Zamora, J. Vazquez, J. Org.
Chem. 1997, 62, 5144 ± 5155.
Â
[8] J. M. Lassaletta, R. Fernandez, E. Martín-Zamora, C. Pareja, Tetra-
[*] Prof. Dr. R. Zenobi, E. Lehmann
Laboratorium für Organische Chemie, ETH Zentrum
Universitätstrasse 16, CH-8092 Zürich (Switzerland)
Fax: (41)1-632-1292
hedron Lett. 1996, 37, 5787 ± 5790.
[9] Suitable crystals were obtained from light petroleum ether at room
temperature. C22H25F3N2O2, Mr 406.44, crystal size 0.1 Â 0.4 Â
0.4 mm, crystal system orthorombic, space group P212121, a
7.4267(10), b 14.081(2), c 20.344(3) , V 2127.5(5) 3, Z 4,
3
[**] We thank Stefan Vetter for many fruitful discussions, Dr. Christophe
Masselon for taking FTICR mass spectra, and the Kommission für
Technologie und Innovation (KTI, project 3165,1) for financial
1calcd 1.269 gcm
,
1.76 < V< 23.328, MoKa radiation (l
0.71073 ), T 296(2) K; of 4500 reflections collected, 2830 were
independent [I > 2d(I)]; 362 parameters, R 0.0682 (wR 0.1100).
The crystal was coated with resin epoxy and mounted in a CCD
diffractometer. The intensities were corrected for Lorentz and
Â
support. E.L. gratefully acknowledges a Kekule doctoral stipend
from the Fonds der Chemischen Industrie.
3430
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
1433-7851/98/3724-3430 $ 17.50+.50/0
Angew. Chem. Int. Ed. 1998, 37, No. 24