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Synlett 2010(19): 2875-2878  
DOI: 10.1055/s-0030-1259026
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Azaviridins as New Scaffolds for the Development of PI-3K Inhibitors

Teather J. Sundstrom, Dennis L. Wright*
Department of Pharmaceutical Sciences, University of Connecticut, Storrs CT, 06269, USA
Fax: +1(860)4866857; e-Mail: dennis.wright@uconn.edu;
Further Information

Publication History

Received 5 August 2010
Publication Date:
10 November 2010 (online)

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Abstract

We have designed a new class of non-natural furanosteroids to serve as more chemically stable analogues of the viridins, potent inhibitors of PI-3K. Central to the design is the incorporation of a nitrogen atom into the steroidal ring system to attenuate the activity of the electrophilic 2,4-diacylfuran common to these natural products. In this manuscript, we describe our initial synthetic studies on this ring system and the preparation of key intermediates for analogue generation.

Key words

natural products - heterocycles - furans - amination - palladium

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12

Selected Characterization Data for Compound 18
¹H NMR (500 MHz, CD3OD): δ = 9.10 (s, 1 H), 8.29 (d, J = 8.8 Hz, 1 H), 8.25 (s, 1 H), 7.84 (d, J = 8.8 Hz, 1 H), 4.43 (q, J = 7.1 Hz, 2 H), 1.44 (t, J = 7.1 Hz, 3 H). ¹³C NMR (125 MHz, CD3OD): δ = 167.5, 152.6, 150.4, 133.2, 129.8, 129.7, 125.9, 125.3, 119.9, 119.5, 103.4, 79.6, 62.6, 14.8. IR (KBr): 3087, 2964, 1633, 1598, 1573 cm-¹. HRMS-FAB: m/z calcd for C14H11BrNO6 [M + H]+: 335.9866; found: 335.9866.

13

Selected Characterization Data for Compound 20
¹H NMR (500 MHz, CDCl3): δ = 9.26 (d, J = 1.9 Hz, 1 H), 8.29 (dd, J = 2.0 Hz, 1 H), 7.52 (s, 1 H), 7.35 (d, J = 8.9 Hz, 1 H), 6.63 (dt, J = 2.2, 10.1 Hz, 1 H), 6.00 (dt, J = 3.3, 10.1 Hz, 1 H), 4.99 (s, 2 H), 4.42 (q, J = 7.1 Hz, 2 H), 1.44 (t, J = 7.1 Hz, 3 H). ¹³C NMR (125 MHz, CDCl3): δ = 166.2, 164.7, 142.0, 141.8, 137.1,136.5, 132.4,130.2, 127.2, 124.5, 123.1, 115.9, 113.6, 111.9, 61.4, 46.6, 14.7. ESI-HRMS: m/z calcd for C17H14NO4 [M + H]+: 296.0923; found: 296.0917.