ACS Combinatorial Science
Research Article
Table 2. Physiochemical and Structural Properties of Azaphilone Libraries
MW
(median, range)
LogD
(median, range)
PSA
(median, range)
H-acceptor
(median, range)
H-donor
(median, range)
rotatable bond
(median, range)
library
Chemset 1
Chemset 2
Chemset 3
293, 232−377
338, 248−428
426, 383−469
1.1, 0−1.6
2, 1.4−2.7
3.5, 3.3−3.6
87, 63−101
86, 64−109
89, 76−101
5, 1−2
5.5, 4−7
5.5, 5−6
1, 1−2
0.5, 0−1
0, 0−0
2.5, 1−7
6.5, 3−10
8.5, 8−9
the solution was stirred at room temperature for 24−48 h.
Filtration over Celite eluting with CH2Cl2 afforded Chemset 2.
11{1,4}. 1H NMR (400 MHz, CDCl3) δ 7.94 (1H, s), 7.35−
7.31 (3H, m), 7.27−7.23 (2H, m), 6.14 (1H, s), 5.58 (1H, s),
3.01 (2H, t, J = 7.8 Hz), 2.78−2.74 (2H, 2dt, J = 10 Hz), 2.45
(2H, t, J = 7.4 Hz), 1.69−1.61 (2H, m), 1.59 (3H, s), 1.48−
1.39 (2H, m), 1.00 (3H, t, J = 7.8 Hz). 13C NMR (75.0 MHz,
CDCl3) δ 193.3, 192.7, 172.0, 162.4, 154.0, 142.8, 140.2, 128.4,
128.2, 126.2, 115.1, 108.6, 106.7, 84.4, 34.8, 32.7, 30.5, 28.5,
22.2, 22.0, 13.6. IR (thin film) 2985, 1734, 1716, 1619, 1543,
1456. HRMS calculated for C23H25O5, 381.1702; found,
381.1728 (M + H).
ASSOCIATED CONTENT
* Supporting Information
■
S
Synthesis and characterization of alkynyl benzaldehydes,
synthesis and characterization of Chemset 1, synthesis and
characterization of 5-bromoazaphilones, cross coupling of
azaphilone scaffolds, synthesis and characterization of Chemset
2, synthesis and characterization of Chemset 3, synthesis and
characterization of additional azaphilones, representative NMR
spectra. This material is available free of charge via the Internet
AUTHOR INFORMATION
Corresponding Author
*Phone: 617-353-2493. Fax: 617-358-2847. E-mail: porco@bu.
■
General Procedure B for the Synthesis of Chemset 2.
To a solution of azaphilone (1 equiv) was added acid chloride
(2 equiv), and the mixture was stirred for 3 min. PS-DMAP (2
equiv (0.35 mmol/g)) was added to the reaction mixture, and
the solution was heated under microwave conditions (80 °C, 15
min, 300 W, stirring on, cooling on). Filtration over Celite
eluting with CH2Cl2 afforded Chemset 2.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the NIGMS (P41 GM076263 and P50
GM067041) is gratefully acknowledged. We thank Professors
John Snyder, Scott Schaus, and James Panek (Boston
University) for helpful discussions. We also thank Dr. Andrew
Germain, Dr. Jianglong Zhu, and Dan Bruggemeyer (Boston
University) for helpful discussions.
1
11{1,5}. H NMR (400 MHz, CDCl3) δ 9.53 (1H, s), 8.31
(1H, dd, J = 1.5, 8.6 Hz), 8.17 (1H, dd), 7.94 (1H, s), 7.92−
7.83 (2H, m), 6.15 (1H, s), 5.60 (1H, s), 2.43 (2H, t, J = 7.8
Hz), 1.81 (3H, s), 1.66−1.59 (2H, m), 1.45−1.36 (2H, m),
0.96 (3H, t, J = 7.0 Hz). 13C NMR (75.0 MHz, CDCl3) δ
192.5, 191.6, 163.0, 162.7, 154.2, 145.2, 143.7, 143.0, 141.7,
141.5, 132.5, 131.0, 130.8, 129.2, 115.2, 108.6, 106.7, 86.2, 32.8,
28.5, 22.5, 22.0, 13.66.
REFERENCES
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3.87 (3H, s), 2.52−2.45 (2H, m), 2.17 (2H, t, J = 7.8 Hz), 1.54
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dx.doi.org/10.1021/co300002x | ACS Comb. Sci. 2012, 14, 236−244