3
therapeutic antineoplastic agents. Chem. Biol. Drug Des. 2018,
91, 681-690.
2944, 1673, 1589, 1433, 1360, 1274, 1255, 1158, 1058, 990 cm–
1; HRMS (ESI) calcd. for C14H12NO3 [M+H]+ 242.0817, found
242.0824.
2.
3.
Yu Feng, Jun Liu, Yazmin P. Carrasco, John B. MacMillan, and Jef
K. De Brabander. Rifamycin Biosynthetic Congeners: Isolation and
Total Synthesis of Rifsaliniketal and Total Synthesis of
Salinisporamycin and Saliniketals A and B. J. Am. Chem. Soc. 2016,
138, 7130−7142.
Steffen Lang, Ulrich Groth. Total Syntheses of Cytotoxic, Naturally
Occurring Kalasinamide, Geovanine, and MarcanineꢀA. Angew.
Chem. Int. Ed. 2009, 48, 911-913.
12. (E)-N-(3-methoxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)but-2-
enamide (19). 1H NMR (500 MHz, CDCl3) δ 8.07 (d, J = 7.3 Hz, 1H),
8.04 (d, J = 7.2 Hz, 1H), 7.72 (dd, J = 7.1, 7.1 Hz, 1H), 7.69 (dd, J =
7.4, 7.4 Hz, 1H), 7.39 (broad s, 1H), 7.00 (dq, J = 15.2, 6.9 Hz, 1H),
6.07 (d, J = 15.3 Hz, 1H), 4.18 (s, 3H), 1.93 (d, J = 6.9 Hz, 3H); 13
C
NMR (126 MHz, CDCl3) δ 182.4, 181.4, 163.5, 150.3, 143.2, 134.2,
133.9, 131.6, 130.5, 127.0, 126.7, 126.4, 124.7, 60.6, 18.1. IR
(neat) 3243, 3015, 1669, 1640, 1620, 1593, 1582, 1525, 1445,
1336, 1317, 1300, 1264, 1213, 1193, 1041, 1010, 966 cm–1; HRMS
(ESI) calcd. for C15H14NO4 [M+H]+ 272.0923, found 272.0925.
13. (E)-N-(3-chloro-1,4-dioxo-1,4-dihydronaphthalen-2-yl)but-2-
enamide (20). mp 116-117 ˚C; 1H NMR (500 MHz, CDCl3) δ 8.20
(dd, J = 7.0, 1.2 Hz, 1H), 8.12 (dd, J = 7.3, 1.1 Hz, 1H), 7.79 (ddd, J
= 7.3, 7.3, 1.2 Hz, 1H), 7.76 (ddd, J = 7.4, 7.4, 1.3 Hz, 1H), 7.71
(broad s, 1H), 7.08 (dq, J = 15.2, 6.9 Hz, 1H), 6.09 (dd, J = 15.2, 1.5
Hz, 1H), 1.97 (dd, J = 6.9, 1.4 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ
180.1, 177.8, 162.2, 145.0, 139.4, 135.0, 134.2, 132.8, 131.8,
130.4, 127.7, 127.2, 124.4, 18.3; IR (neat) 3247, 1687, 1669, 1647,
1616, 1591, 1515, 1334, 1308, 1288, 1249, 1206, 1101, 977 cm–1;
HRMS (ESI) calcd. for C14H10NO3Na35Cl [M+Na]+ 298.0247, found
298.0252; calcd. for C14H10NO3Na37Cl [M+Na]+ 300.0217, found
300.0232.
14. General procedure for the hydrogenation coupling oxidation
protocol: To a solution of 2-amino-1,4-naphthaquinone (87 mg,
0.5 mmol) in THF (6 mL) at rt was added 10% Pd/C (9 mg). The
resulting mixture was charged with H2 gas (1 atm) and allowed to
stir overnight. After this time period the H2 balloon was removed
and the reaction mixture was purged with N2 for 5 min. To the
resulting reaction mixture was added a solution of the acid
chloride (0.55 or 1.00 mmol) in CH2Cl2 (2 mL) via syringe. The
resulting mixture was stirred at rt for 10 min and NaHCO3 (46 mg,
0.55 mmol or 84 mg, 1 mmol) was added. After stirring for an
additional 10 min the reaction mixture was passed through a
short pad of Celite using EtOAc (20 mL). The filtrate was then
exposed to the atmosphere at rt for 1 day. The reaction mixture
was concentrated and the resulting residue was purified using
flash column chromatography (hexanes:ethyl acetate).
4. Yin, J.; Landward, M.B.; Rainier, J. D. Photoelectrocyclization
Reactions of Amidonaphthoquinones. J. Org. Chem. 2020, 85, In
Press.
5.
E. J. Corey, David A. Clark. Studies on the total synthesis of
rifamycin. A method for the closure of the macrocyclic unit.
Tetrahedron. Lett. 1980, 21, 2045–2048.
6. Fieser, L.F.; Hartwell, J.L. The Reaction of Hydrazoic Acid with the
Naphthoquinones. J. Am. Chem. Soc. 1935, 57, 1482-1484.
7. Compound 18 is known, see: Zhang, C.; Chou, J.C. Metal-Free
Direct Amidation of Naphthoquinones Using Hydroxamic Acids as
an Amide Source: Application in the Synthesis of an HDAC6
Inhibitor. Org. Lett. 2016, 18, 5512-5515.
8. For the synthesis of the aminoquinone that leads to 19 see: (a)
Brandy, Y.; Brandy, N.; Akinboye, E.; Lewis, M.; Mouamba, C.;
Mack, S.; Butcher, R.; Anderson, A.J.; Bakare, O. Synthesis and
Characterization of Novel Unsymmetrical and Symmetrical 3-
Halo- or 3-Methoxy-substituted 2-Dibenzoylamino-1,4-
naphthoquinone Derivatives. Molecules 2013, 18, 1973-1984. (b)
Bakare, O.; Ashendel, C.L.; Peng, H.; Zalkow, L.H.; Burgess, E.M.
Synthesis and MEK1 inhibitory activities of imido-substituted 2-
Chloro-1,4-naphthoquinone. Bioorg. Med. Chem. 2003, 11, 3165-
3170.
9. For the synthesis of the aminoquinone that leads to 20 see: Diaz,
R.; Reyes, O.; Francois, A.; Leiva, A.M.; Loeb, B. Synthesis of a new
polypyridinic highly conjugated ligand with electron-acceptor
properties. Tetrahedron Lett. 2001, 43, 5353-6467.
10. (E)-N-(1,4-dioxo-1,4-dihydronaphthalen-2-yl)-2,5-dimethylhexa-
2,4-dienamide (16). mp 169-173 ˚C; 1H NMR (500 MHz, CDCl3) δ
8.85 (broad s, 1H), 8.10 (dd, J = 7.8, 1.1 Hz, 2H), 7.91 (s, 1H), 7.77
(ddd, J = 7.5, 7.5, 1.2 Hz, 1H), 7.71 (ddd, J = 7.5, 7.5, 1.2 Hz, 1H),
7.36 (d, J = 11.6 Hz, 1H), 6.16 (d, J = 11.6 Hz, 1H), 2.07 (s, 3H),
1.94 (s, 6H). 13C NMR (126 MHz, CDCl3) δ 185.4, 181.6, 168.0,
146.3, 140.4, 135.1, 133.4, 133.3, 132.4, 130.1, 126.7, 126.5,
126.3, 120.9, 116.8, 27.2, 19.2, 12.6; IR (neat) 3370, 2916, 2861,
1665, 1641, 1628, 1590, 1578, 1503, 1477, 1446, 1380, 1333,
1297, 1226, 1199, 1157, 1095 cm–1; HRMS (ESI) calcd. for
C18H18NO3 [M+H]+ 296.1287, found 296.1293.
11. N-(1,4-dioxo-1,4-dihydronaphthalen-2-yl)but-3-enamide (17). mp
158-160 ˚C; 1H NMR (500 MHz, CDCl3) δ 8.55 (broad s, 1H), 8.10
(partially obscured dd, J = 7.7, 0.9 Hz, 1H), 8.09 (partially
obscured dd, J = 7.7, 1.2 Hz, 1H), 7.85 (s, 1H), 7.78 (ddd, J = 7.5,
7.5, 1.3 Hz, 1H), 7.71 (ddd, J = 7.6, 7.6, 1.3 Hz, 1H), 6.02 (ddt, J =
17.2, 10.1, 7.1 Hz, 1H), 5.40 (dd, J = 10.4, 1.0 Hz, 1H), 5.37 (dd, J =
17.2, 1.3 Hz, 1H) 3.27 (d, J = 7.1 Hz, 2H); 13C NMR (126 MHz,
CDCl3) δ 185.3, 181.2, 170.0, 139.9, 135.1, 133.4, 132.3, 130.1,
129.8, 126.8, 126.6, 121.5, 117.4, 43.1; IR (neat) 3202, 3069,
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