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Synlett 2006(2): 247-250  
DOI: 10.1055/s-2005-923595
LETTER
© Georg Thieme Verlag Stuttgart · New York

Aryldiazirine-Modified Pyroglutamates: Photoaffinity Labels for Glutamate

Emilie L. Bentz, Hannah Gibson, Clare Hudson, Mark G. Moloney*, Debbie A. Seldon, Edwina S. Wearmouth
The Department of Chemistry, Chemistry Research Laboratory, The University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK
Fax: +44(1865)285002; e-Mail: mark.moloney@chem.ox.ac.uk;
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Publication History

Received 13 October 2005
Publication Date:
23 December 2005 (online)

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Abstract

The synthesis of an aryldiazirine-modified pyroglutamate is reported for potential application as a photoaffinity label at glutamate receptors. Detailed 13C NMR and 19F NMR spectroscopic characterisation data for these trifluoromethyl-substituted aryldiazirines has been determined and shown to be useful for tracking this group during synthesis.

Key words

glutamate - photoaffinity - diazirines

36

Data for Lactam 5.
Obtained as a colourless oil (0.111 g, 23%); R f = 0.20 [PE(40-60 °C)-EtOAc, 5:1]. 1H NMR (400 MHz, CDCl3): δ = 1.30 (3 H, t, J = 7.0 Hz, CH3CH2), 1.47 [9 H, s, C(CH3)3], 2.66 (2 H, d, J = 7.6 Hz, CH2CO2 t-Bu), 3.09-3.15 [1 H, m, H(6)], 3.23 (2 H, dd, J = 13.9 Hz, CH2Ph), 3.33 (3 H, s, OCH3), 3.60-3.66 [1 H, m, H(5)], 3.76-4.26 [2 H, m, H(4)], 4.30-4.34 (2 H, m, CH3CH2), 6.21 [1 H, s, H(2)], 6.39 (1 H, s, ArH ortho to OMe)], 6.47 (1 H, d, J = 8.0 Hz, ArH para to OMe), 7.23 (1 H, d, J = 8.0 Hz, ArH meta to OMe), 7.27-7.44 (5 H, m, PhH). 13C NMR (400 MHz, CDCl3): δ = 14.1 (CH3CH2), 28.1 [C(CH3)3], 28.3 (CH2Ph), 33.9 (CH2CO2 t-Bu), 45.9 [C(6)], 54.7 (OCH3), 61.9 [C(5)], 62.0 (CO2CH2CH3), 63.9 [C(7)], 72.8 [C(4)], 86.9 [C(2)], 107.8 (ArC ortho to OMe), 118.3 (ArH para to OMe), 126.0, 126.5, 128.4, 128.7, 128.9 (all ArCH), 127.4 (q, J = 280.5 Hz, CF3), 126.1, 129.1 (ArC), 132.6 [C(15)], 138.3 [(C(13)], 157.6 [C(11)], 170.6 (lactam C=O), 170.8 (ethyl ester C=O), 171.7 (t-Bu ester C=O). IR (thin film): νmax = 2981 (s, aliphatic C-H), 1728 (br s, ester and lactam C=O), 1261 (s, C-O), 1039 (s, C-F) cm-1.

37

Data for Lactam 6.
Obtained as a colourless oil (0.0198 g, 24%). R f = 0.23 [EtOAc-PE (40-60 °C), 6:5]. 1H NMR ( 400 MHz, CDCl3): δ = 2.73-2.85 (2 H, m, CH2CO2Me), 3.22 (2 H, dd, J = 14.7 Hz, CH2Ph), 3.52-3.62 [1 H, m, H(3)], 3.70, 3.74, 3.77, 3.79 (4 × 3 H, s, OCH3), 3.69-3.76 [1 H, m, H(2)], 6.31 (1 H, s, NH), 6.55 (1 H, s, ArH ortho to OMe), 6.69 (1 H, d, J = 7.9 Hz, ArH para to OMe), 7.37 (1 H, d, J = 8.0 Hz, ArH meta to OMe). 13C NMR (400 MHz, CDCl3): δ = 27.2 (CH2Ph), 28.6 [C(3)], 32.3 (CH2CO2Me), 43.9 [C(2)], 52.0, 52.8, 53.0 (OCH3), 55.2 (ArOCH3), 58.6 [C(4)], 108.0 (ArC ortho to OMe), 118.7 (ArC para to OMe), 122.0 (q, J = 274.7 Hz, CF3), 126.2 (ArC ortho to OMe), 129.3 (ΑρΧ), 131.7 (ΑρΧ), 157.6 [Χ(8)], 170.3, 170.7, 171.4 (Χ=Ο εστερσ), 173.0 (Χ=Ο λαχταµ). ΙΡ (τηιν φιλµ): νmax = 3020, 2956 (m, C-H), 2401 (m, N=N), 1740 (s, C=O), 1577, 1515 (m, Ar C=C), 1216 (s, C-O), 1039 (s, C-F) cm-1.