Total Synthesis of the (+)-Antimycin A Family
(sept., J = 7.1 Hz, 1 H), 2.54 (ddd, J = 11.4, 10.2, 2.7 Hz, 1 H), 1 H), 7.07 and 7.06 (d, J = 7.8 and d, J = 11.4 Hz, total integr. 1
1.74–1.66 (m, 1 H), 1.40–1.10 (m, 9 H), 1.32 (d, J = 6.6 Hz, 3 H), H), 6.92 and 6.90 (t, J = 7.8, and t, J = 7.8 Hz, total integr. 1 H),
1.28 (d, J = 6.0 Hz, 3 H), 1.22 (dd, J = 7.2, 2.7 Hz, 6 H), 0.86 (t,
J = 7.1 Hz, 3 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 175.6,
172.9, 170.1, 169.3, 159.1, 150.6, 127.4, 124.8, 120.1, 119.0, 112.5,
75.2, 74.9, 70.8, 53.6, 50.1, 34.1, 31.5, 28.9, 28.3, 27.0, 22.5, 18.9,
5.73 (dq, J = 6.6, 6.6 Hz, 1 H), 5.29 and 5.28 (t, J = 7.8 and t, J
= 7.2 Hz, total integr. 1 H), 5.10 and 5.09 (t, J = 10.2 and t, J =
10.2 Hz, total integr. 1 H), 4.99 (dq, J = 10.2, 6.0 Hz, 1 H), 2.51
(ddd, J = 13.8, 11.4, 3.0 Hz, 1 H), 2.26 (dd, J = 7.8, 2.4 Hz, 2 H),
2.14 (sept., J = 7.8 Hz, 1 H), 1.75–1.65 (m, 1 H), 1.45–1.10 (m, 5
H), 1.33 (d, J = 6.5 Hz, 3 H), 1.30 (d, J = 6.6 Hz, 3 H), 0.99 (dd,
J = 7.2, 1.8 Hz, 6 H), 0.87 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR
(150 MHz, CDCl3): δ = 173.0, 171.7, 170.1, 169.4, 159.0, 150.6,
127.4, 124.8, 120.1, 119.0, 112.5, 111.3, 75.4, 74.9, 70.9, 53.7, 50.1,
43.2, 29.2, 28.2, 25.5, 22.43, 22.40, 17.9, 15.0, 13.8 ppm. IR (neat):
17.8, 15.0, 14.0 ppm. IR (ATR): ν = 3348, 2930, 1740, 1640, 1608,
˜
1527, 1362, 1181, 1141, 1067. MS (CI): m/z = 535 [M + H]+ (base
peak), 447, 357, 303, 271, 265, 181. HRMS (CI): calcd. for
C27H39N2O9 [M + H]+ 535.2655; found 535.2662.
Antimycin A2b: Colorless needles (rotameric mixture); m.p. 142.6–
144.7 °C (n-hexane/CH2Cl2). [α]2D5 = +72.3 (c = 0.209, MeOH). H
1
ν = 3370, 1750, 1692, 1644, 1611 cm–1. MS (CI): m/z = 520 [M]+,
˜
NMR (600 MHz, CDCl3): δ = 12.63 and 12.48 (s and s, total integr.
1 H), 8.79 and 8.52 (d, J = 11.5 and d, J = 1.6 Hz, total integr. 1
H), 8.56 and 7.38 (dd, J = 7.8, 1.1 and br. d, J = 8.0 Hz, total
integr. 1 H), 8.01 and 7.78 (br. s and br. d, J = 8.0 Hz, total integr.
1 H), 7.29 and 7.25 (br. d, J = 8.2 and dd, J = 7.8, 1.4 Hz, total
458, 418, 264, 236, 220, 202 (base peak). HRMS (CI): calcd. for
C26H36N2O9 [M]+ 520.2421; found 520.2454.
Antimycin A4a: Colorless needles (rotameric mixture); m.p. 179.3–
1
180.4 °C (n-hexane/CH2Cl2). [α]2D5 = +77.0 (c = 0.208, MeOH). H
integr. 1 H), 7.09 and 7.07 (d, J = 7.7 and d, J = 8.0 Hz, total NMR (600 MHz, CDCl3): δ = 12.63 and 12.48 (s and s, total integr.
integr. 1 H), 6.92 and 6.90 (t, J = 8.0 and t, J = 8.0 Hz, total integr. 1 H), 8.79 and 8.52 (d, J = 11.5 and d, J = 1.6 Hz, total integr. 1
1 H), 5.75 (dq, J = 7.8, 7.8 Hz, 1 H), 5.31 and 5.29 (t, J = 7.7 and
t, J = 7.7 Hz, total integr. 1 H), 5.11 and 5.10 (t, J = 9.9 and t, J
= 12.6 Hz, total integr. 1 H), 4.99 (dq, J = 10.2, 6.6 Hz, 1 H), 2.52
(ddd, J = 13.2, 10.8, 2.7 Hz, 1 H), 2.36 (td, J = 7.2, 1.6 Hz, 1 H),
H), 8.56 and 7.38 (dd, J = 7.9, 1.1 and br. d, J = 8.0 Hz, total
integr. 1 H), 8.02 and 7.78 (br. s and br. d, J = 11.5 Hz, total integr.
1 H), 7.29 and 7.25 (br. d, J = 8.0 and dd, J = 8.2, 1.4 Hz, total
integr. 1 H), 7.09 and 7.06 (d, J = 7.8 and d, J = 8.2 Hz, total
1.75–1.64 (m, 3 H), 1.38–1.12 (m, 9 H), 1.32 (d, J = 6.9 Hz, 3 H), integr. 1 H), 6.92 and 6.90 (t, J = 8.2 and t, J = 8.2 Hz, total integr.
1.29 (d, J = 6.0 Hz, 3 H), 0.99 (t, J = 7.1 Hz, 3 H), 0.87 (t, J = 1 H), 5.76 (dq, J = 7.7, 6.6 Hz, 1 H), 5.32 and 5.29 (t, J = 7.7 and
7.1 Hz, 3 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 172.9, 172.3,
170.1, 169.3, 159.1, 150.6, 127.4, 124.8, 120.1, 119.0, 112.5, 75.4,
74.9, 70.9, 53.6, 50.1, 36.1, 31.5, 28.9, 28.4, 27.0, 22.5, 18.3, 17.8,
t, J = 7.7 Hz, total integr. 1 H), 5.11 and 5.08 (t, J = 9.9 and t, J
= 10.2 Hz, total integr. 1 H), 5.00 (dq, J = 9.6, 6.3 Hz, 1 H), 2.62
(sept., J = 7.1 Hz, 1 H), 2.54 (ddd, J = 11.4, 10.2, 3.0 Hz, 1 H),
1.75–1.65 (m, 1 H), 1.37–1.10 (m, 5 H), 1.31 (d, J = 6.6 Hz, 3 H),
1.28 (d, J = 6.6 Hz, 3 H), 1.22 (dd, J = 8.5, 2.7 Hz, 6 H), 0.88 (t,
J = 6.9 Hz, 3 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 175.6,
172.4, 170.1, 169.3, 159.1, 150.6, 127.4, 124.8, 120.1, 119.0, 112.5,
75.2, 74.9, 70.9, 53.6, 50.1, 34.1, 29.2, 28.0, 22.4, 19.0, 17.8, 15.0,
15.0, 14.0, 13.7 ppm. IR (ATR): ν = 3351, 2929, 1739, 1673, 1636,
˜
1610, 1526, 1205, 1163 cm–1. MS (CI): m/z = 535 [M + H]+ (base
peak), 447, 357, 303, 271, 265, 181. HRMS (CI): calcd. for
C27H39N2O9 [M + H]+ 535.2655; found 535.2664.
Antimycin A3a: Colorless needles (rotameric mixture); m.p. 173.0–
174.0 °C (petroleum ether/Et2O). [α]2D3 = +91.6 (c = 0.320, CHCl3).
1H NMR (600 MHz, CDCl3): δ = 12.63 and 12.47 (s and s, total
integr. 1 H), 8.79 and 8.51 (d, J = 11.4 and d, J = 1.2 Hz, total
integr. 1 H), 8.55 and 7.38 (dd, J = 7.8, 1.2 and br. d, J = 7.2 Hz,
total integr. 1 H), 7.98 and 7.78 (br. s and br. d, J = 11.4 Hz, total
integr. 1 H), 7.30 and 7.25 (br. d, J = 7.2 and dd, J = 7.8, 1.2 Hz,
total integr. 1 H), 7.09 and 7.07 (br. d, J = 7.2 and br. d, J =
13.8 ppm. IR (ATR): ν = 3369, 2956, 1745, 1687, 1642, 1528, 1363,
˜
1180, 1141, 1067 cm–1. MS (CI): m/z = 507 [M + H]+, 506 [M]+,
419, 265, 247, 56 (base peak). HRMS (CI): calcd. for C25H35N2O9
[M + H]+ 507.2342; found 507.2342.
Antimycin A4b: Colorless solid (rotameric mixture); m.p. 186.2–
1
187.1 °C. [α]2D3 = +76.3 (c = 0.211, MeOH). H NMR (600 MHz,
CDCl3): δ = 12.63 and 12.48 (s and s, total integr. 1 H), 8.79 and
7.2 Hz, total integr. 1 H), 6.92 and 6.90 (t, J = 7.8 and t, J = 8.52 (d, J = 11.5 and d, J = 1.8 Hz, total integr. 1 H), 8.56 and
7.8 Hz, total integr. 1 H), 5.75 (dq, J = 7.8, 6.6 Hz, 1 H), 5.31 and
5.29 (t, J = 7.8 and t, J = 7.2 Hz, total integr. 1 H), 5.11 and 5.09
(t, J = 10.2 and t, J = 10.2 Hz, total integr. 1 H), 5.00 (dq, J = 9.6,
6.6 Hz, 1 H), 2.53 (ddd, J = 12.0, 10.2, 3.6 Hz, 1 H), 2.43 (sext., J
7.38 (dd, J = 8.0, 0.8 and br. d, J = 8.2 Hz, total integr. 1 H), 8.03
and 7.79 (br. s and br. d, J = 8.2 Hz, total integr. 1 H), 7.29 and
7.23 (br. d, J = 8.0 and dd, J = 8.2, 1.1 Hz, total integr. 1 H), 7.09
and 7.07 (d, J = 7.4 and d, J = 8.0 Hz, total integr. 1 H), 6.92 and
= 7.8 Hz, 1 H), 1.75–1.67 (m, 2 H), 1.50 (ddq, J = 14.4, 7.8, 7.2 Hz, 6.90 (t, J = 8.2 and t, J = 8.0 Hz, total integr. 1 H), 5.75 (dq, J =
1 H), 1.40–1.05 (m, 5 H), 1.32 (d, J = 6.6 Hz, 3 H), 1.29 (d, J = 7.7, 6.6 Hz, 1 H), 5.32 and 5.29 (t, J = 7.8 and t, J = 7.7 Hz, total
6.6 Hz, 3 H), 1.19 (d, J = 6.6 Hz, 3 H), 0.95 (dd, J = 7.8, 7.2 Hz,
3 H), 0.87 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3):
δ = 175.3, 173.0, 170.0, 169.3, 159.1, 150.6, 127.4, 124.8, 120.1,
integr. 1 H), 5.11 and 5.10 (t, J = 10.2 and t, J = 10.2 Hz, total
integr. 1 H), 4.99 (dq, J = 9.6, 6.3 Hz, 1 H), 2.51 (ddd, J = 12.3,
11.4, 3.0 Hz, 1 H), 2.36 (td, J = 7.4, 1.6 Hz, 2 H), 1.75–1.64 (m, 3
119.0, 112.5, 75.2, 74.9, 70.9, 53.6, 50.1, 41.2, 29.2, 28.1, 26.4, 22.4, H), 1.40–1.15 (m, 5 H), 1.32 (d, J = 6.6 Hz, 3 H), 1.29 (d, J =
17.8, 16.8, 15.0, 13.8, 11.7 ppm. IR (neat): ν = 3370, 2963, 2875, 6.3 Hz, 3 H), 0.99 (t, J = 7.4 Hz, 3 H), 0.87 (t, J = 7.4 Hz, 3
1747, 1684, 1644, 1604, 1537 cm–1. MS (CI): m/z = 521 [M + H]+, H) ppm. 13C NMR (150 MHz, CDCl3): δ = 172.9, 172.3, 170.1,
˜
419, 329, 278, 236, 91 (base peak). HRMS (CI): calcd. for
169.3, 159.1, 150.6, 127.4, 124.8, 120.1, 119.0, 112.5, 75.4, 74.9,
70.9, 53.6, 50.1, 36.0, 29.2, 28.1, 22.4, 18.3, 17.8, 15.0, 13.8,
C26H37N2O9 [M + H]+ 521.2463; found 521.24988.
13.7 ppm. IR (ATR): ν = 3363, 2960, 1741, 1693, 1640, 1528, 1360,
˜
Antimycin A3b: Colorless needles (rotameric mixture); m.p. 183.5–
184.0 °C (petroleum ether/Et2O). [α]2D2 = +84.3 (c = 1.01, CHCl3).
1H NMR (600 MHz, CDCl3): δ = 12.63 and 12.47 (s and s, total
integr. 1 H), 8.79 and 8.51 (d, J = 11.4 and d, J = 1.8 Hz, total
integr. 1 H), 8.56 and 7.38 (dd, J = 7.8, 1.2 and d, J = 7.8 Hz, total
integr. 1 H), 7.94 and 7.76 (br. s and br. d, J = 9.5 Hz, total integr.
1 H), 7.29 and 7.24 (d, J = 7.2 and dd, J = 8.4, 1.2 Hz, total integr.
1250, 1149 cm–1. MS (FAB): m/z = 507 [M + H]+ (base peak), 489,
419, 265, 243, 181, 155. HRMS (FAB): calcd. for C25H35N2O9 [M
+ H]+ 507.2342; found 507.2342.
Antimycin A9: Pale-yellow solid (rotameric mixture); m.p. 151.1–
1
151.8 °C. [α]2D2 = +82.1 (c = 0.171, MeOH). H NMR (600 MHz,
CDCl3): δ = 12.61 and 12.47 (s and s, total integr. 1 H), 8.79 and
Eur. J. Org. Chem. 2011, 2719–2729
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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