1741, 1697, 1463, 1378, 1258, 1158, 1096, 1044, 835 and 776;
δH (500 MHz, CDCl3) −0.11, 0.09, 0.117 and 0.121 (each 3 H,
s, SiCH3), 0.85 and 0.96 [each 9 H, s, SiC(CH3)3], 0.99 (3 H, d,
J 7.0, 9-CH3), 1.11 (3 H, d, J 7.0, 7-CH3), 1.15 and 1.21 (each
3 H, s, 5-CH3), 1.48–1.64 (3 H, m), 1. 69 (3 H, s, 13-CH3),
1.69–1.76 (2 H, m), 2.04–2.10 (2 H, m), 2.11 (3 H, s, 1′-CH3),
2.48 (1 H, m), 2.64–2.75 (2 H, m, 3-H, 15-H), 2.75 (3 H, s, 2′′-
CH3), 2.87 (1 H, br. d, J 16.0, 3-H), 3.04 (1 H, m, 7-H), 3.90
(1 H, d, J 9.0, 8-H), 4.02 (1 H, d, J 10.0, 4-H), 4.89 (1 H, d,
J 10.0, 16-H), 5.18 (1 H, t, J 8.0, 14-H), 6.60 (1 H, s, 2′-H) and
6.99 (1 H, s, 5′′-H); δC (75 MHz, CDCl3) −5.7, −3.8, −3.4,
15.3, 17.7, 18.5, 18.6, 19.2, 23.0, 24.2, 24.5, 26.0, 26.1, 26.3,
27.4, 29.3, 31.3, 31.9, 32.4, 39.1, 53.3, 76.2, 79.8, 115.8, 119.1
(2) 138.8, 140.5, 152.3, 164.6, 171.2 and 215.1; m/z (CI) 720
(M+ + 1, 100%).
14-H2), 1.58–1.78 (3 H, m, 12-H, 15-H2), 1.90 (1 H, m, 2-H),
2.08 (3 H, s, 1′-CH3), 2.12 (1 H, m, 2-H), 2.35 (1 H, dd, J 14.0,
2.5, 6-H), 2.54 (1 H, dd, J 14.0, 10.5, 6-H), 2.70–2.80 (4 H, m,
OH, 2′′-CH3), 2.80 (1 H, dd, J 7.5, 4.5, 1-H), 3.30 (1 H, dq,
J 7.0, 4.0, 10-H), 3.76 (1 H, dd, J 4.5, 4.0, 11-H), 4.22–4.40
(2 H, m, OH, 7-H), 5.40 (1 H, dd, J 8.0, 2.5, 3-H), 6.62 (1 H, s,
2′-H) and 6.99 (1 H, s, 5′′-H); m/z (CI) 508 (M+ + 1, 1.2%) and
322 (4).
Acknowledgements
We thank E. Kate Hoegenauer for preliminary studies of the
Ireland–Claisen rearrangement and Pfizer for support (to N. M.)
under the CASE scheme.
Notes and references
(4S,7R,8S,9S,13Z,16S)-4,8-Dihydroxy-5,5,7,9,13-pentamethyl-
16-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-1-oxacyclo-
hexadec-13-ene-2,6-dione (Epothilone D) 2.2q Trifluoroacetic
acid (100 μL) was added to the bis-(tert-butyldimethylsilyl)
ether 71 (21 mg, 29.3 μmol) in DCM (150 μL) at 0 °C and the
solution stirred for 6 h. After concentration under reduced
pressure, chromatography of the residue, eluting with DCM–
MeOH (DCM to 3% MeOH in DCM), gave the title compound
2 (13 mg, 91%) as a white foam, [α]2D1 −88.6 (c 0.22 in CHCl3),
lit.2q [α]D22 −91.5 (c 0.3 in CHCl3) (Found: M+, 491.2703.
C27H41NO5S requires M, 491.2705); δH (500 MHz, CDCl3) 1.02
(3 H, d, J 7.0, 9-CH3), 1.07 (3 H, s, 5-CH3), 1.20 (3 H, d, J 7.0,
7-CH3), 1.24–1.34 (4 H, m, 11-H2, 10-H2), 1.38 (3 H, s, 5-CH3),
1. 67 (3 H, s, 13-CH3), 1.77 (1 H, m, 9-H), 1.90 (1 H, m, 12-H),
2.07 (3 H, s, 1′-CH3), 2.22–2.30 (2 H, m, 3-H, 15-H), 2.32 (1 H,
m, 12-H), 2.48 (1 H, dd, J 14.5, 11.5, 3-H), 2.62 (1 H, dt,
J 15.0, 10.0, 15-H), 2.75 (4 H, br. s, OH, 2′′-CH3), 3.09 (1 H, br.
s, OH), 3.19 (1 H, qd, J 7.0, 2.0, 7-H), 3.72 (1 H, dd, J 4.0, 2.0,
8-H), 4.35 (1 H, dd, J 11.5, 4.5, 4-H), 5.14 (1 H, dd, J 10.0, 5.0,
14-H), 5.20 (1 H, d, J 9.0, 16-H), 6.68 (1 H, s, 2′-H) and 7.01
(1 H, s, 5′′-H); δC (75 MHz, CDCl3) 13.3, 15.6, 15.9, 17.8, 18.9,
22.9, 25.3, 30.2, 31.5, 31.7, 32.4, 38.4, 39.5, 41.5, 53.5, 72.1,
74.0, 78.7, 115.5, 120.8, 128.2, 138.4, 151.7, 165.1, 170.3 and
220.6; m/z (CI) 492 (M+ + 1, 100%) and 491 (M+, 5).
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(1S,3S,7S,10R,11S,12S,16R)-7,11-Dihydroxy-8,8,10,12,16-penta-
methyl-3-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-
4,17-dioxabicyclo[14.1.0]heptadecane-5,9-dione (Epothilone B)
1.2p,q A freshly prepared solution of dimethyl dioxirane in
acetone was added to epothilone D 2 (4.2 mg) in DCM at
−50 °C until TLC showed complete consumption of the starting
material. The excess of DMDO and the solvents were removed
by passing a stream of N2 gas through the cold (−50 °C) sol-
ution. The solid residue was shown to be a 4.2 : 1 mixture of dia-
stereoisomeric cis-epoxides by analytical HPLC. Preparative
reverse phase HPLC eluting with 1 : 1 : 1 MeOH–H2O–MeCN
gave the title compound 1 (2.7 mg, 62%, retention time
4.39 min) as white needles, [α]2D0 −33.9 (c 0.13 in CHCl3), lit.2p
[α]D −31.0 (c 0.045 in CHCl3), lit.2q [α]D22 −34.3 (c 0.2 in
MeOH) (Found: M+ + H, 508.2725. C27H42NO6S requires M,
508.2733); δH (500 MHz, CDCl3) 1.00 (3 H, d, J 7.0, 12-CH3),
1.07 (3 H, s, 8-CH3), 1.16 (3 H, d, J 7.0, 10-CH3), 1.28 Ö (3 H,
s, 8-CH3), 1. 37 (3 H, s, 16-CH3), 1.34–1.56 (4 H, m, 13-H2,
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This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 7952–7964 | 7963