Organic & Biomolecular Chemistry
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14.3, 13.9, 11.0. HRMS (ESI) m/z [M + H]+ calcd for C25H32O5Cl thesized as a clear oil from 32 (40 mg, 0.082 mmol) via the
447.1938, found 447.1935. same procedure as described for the synthesis of 10a. Rf = 0.50
(5R,6R)-6-((2R,4R,5S,7S,8E,10E)-11-(2-Chloro-3-hydroxyphenyl)- (SiO2, 8% EtOAc–hexanes); [α]2D5 = +93.84 (c 0.18, CHCl3); IR
5,7-dihydroxy-4-methylundeca-8,10-dien-2-yl)-5-ethyl-5,6-dihydro- (neat): νmax 2928, 2855, 1720, 1648, 1616, 1580, 1460, 1260,
2H-pyran-2-one, {(−)-bitungolide B} (7). To a solution of 31 1192, and 1066 cm−1; 1H NMR (CDCl3, 300 MHz) δ = 7.53–7.44
(8 mg, 0.018 mmol) in anhydrous CH3CN (1.5 mL) at −30 °C (m, 2H), 7.43–7.30 (m, 4H), 7.04–6.78 (m, 2H), 6.44 (dd, J =
were added Me4NBH(OAc)3 (19.7 mg, 0.075 mmol) and glacial 17.2, 1.6 Hz, 1H), 6.30 (d, J = 15.6 Hz, 1H), 6.14 (dd, J = 17.2,
AcOH (1.5 mL) sequentially. The temperature of the reaction 9.9 Hz, 1H), 5.84 (dd, J = 9.9, 1.6 Hz, 2H), 5.46 (ddd, J = 17.2,
was slowly raised to −20 °C, and stirring was continued at this 9.8, 9.0 Hz, 1H), 5.11 (dd, J = 10.7, 2.5 Hz, 1H), 4.96 (m, 1H),
temperature for 3 h. Then the reaction mixture was quenched 4.12 (m, 1H), 2.82 (dd, J = 14.8, 8.2 Hz, 1H), 2.46 (dd, J = 14.8,
with saturated potassium sodium tartrate (2 mL) at 0 °C and 4.1 Hz, 1H), 2.25 (m, 1H), 1.80 (m, 1H), 1.66–1.35 (m, 5H),
stirred at rt for 1 h. The reaction mixture was extracted with 0.91–0.75 (m, 18H), 0.04 (s, 3H), −0.04 (s, 3H); 13C NMR
EtOAc (3 × 5 mL). The combined organic extracts were washed (CDCl3, 75 MHz): δ 200.0, 166.3, 142.9, 141.4, 137.9, 136.0,
with saturated aqueous NaHCO3 (2 mL), water (2 mL), brine 130.8, 130.7, 129.1, 128.8, 128.5, 127.2, 126.7, 117.2, 80.0, 74.0,
(2 mL), dried over Na2SO4, filtered and concentrated under 48.0, 43.9, 36.3, 32.0, 31.6, 25.8, 23.0, 18.0, 16.6, 13.6, 11.4,
vacuum. The residue was purified by column chromatography −4.7, −4.6; HRMS (ESI) m/z calcd for C33H50O4NaSi [M + Na]+:
(SiO2, 40% EtOAc–hexanes) to afford 7 (6 mg, 78% yield) as a 561.3376, found: 561.3369.
white amorphous solid. Rf 0.5 (60% EtOAc in hexanes); [α]D25
– 44.3 (c 0.3 in CHCl3); IR (neat): νmax 3403 (br), 3380 (br), methyl-7-oxo-11-phenylundeca-8,10-dien-2-yl)-5-ethyl-5,6-
2917, 2850, 1701, 1246, 1093, 1034, 830 cm−1 1H NMR dihydro-2H-pyran-2-one (9b). Compound 9b (18 mg, 80%
=
(5R,6R)-6-((2R,4R,5S,8E,10E)-5-(tert-Butyldimethylsilyloxy)-4-
;
(500 MHz, CDCl3) δ = 7.16 (m, 1H), 7.14 (m, 1H), 7.07 (dd, J = yield) was synthesized as a clear oil from 10b (25 mg,
9.8, 6.7 Hz, 1H), 6.90 (m, 1H), 6.88 (d, J = 15.3 Hz, 1H), 6.78 0.046 mmol) via the same procedure as described for the syn-
(dd, J = 14.8, 9.8 Hz, 1H), 6.52 (ddd, J = 15.8, 9.9, 1.9 Hz, 1H), thesis of compound 9a. Rf = 0.43 (SiO2, 15% EtOAc–hexanes);
6.05 (d, J = 9.8 Hz, 1H), 5.96 (dd, J = 15.3, 5.9 Hz, 1H), 5.66 [α]2D5 = −112.20 (c 0.14, CHCl3); IR (neat): νmax 2926, 2855, 1722,
(brs, OH), 4.61 (m, 1H), 3.97 (dd, J = 10.8, 2.9 Hz, 1H), 3.79 (m, 1616, 1589, 1461, 1382, 1250, and 1062 cm−1; 1H NMR (CDCl3,
1H), 2.68 (brs, OH), 2.43 (brs, OH), 2.36 (m, 1H), 1.95 (m, 1H), 300 MHz): δ 7.53–7.42 (m, 2H), 7.42–7.27 (m, 4H), 7.08 (dd, J =
1.84–1.66 (m, 5H), 1.5 (m, 1H), 1.20 (ddd, J = 12.8, 10.8, 1.9 Hz, 9.8, 6.0 Hz, 1H), 7.02–6.82 (m, 2H), 6.29 (d, J = 15.1 Hz, 1H),
1H), 0.96 (t, J = 7.9 Hz, 3H), 0.91 (d, J = 6.9 Hz, 3H), 0.89 (d, J = 6.05 (d, J = 9.8 Hz, 1H), 4.14 (m, 1H), 3.94 (dd, J = 9.8, 3.0 Hz,
6.9 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 164.8, 151.6, 151.1, 1H), 2.85 (dd, J = 14.3, 8.3 Hz, 1H), 2.44 (dd, J = 14.3, 3.0 Hz,
137.8, 135.8, 131.3, 129.9, 128.0, 127.5, 120.9, 119.1, 118.1, 1H), 2.34 (m, 1H), 1.97–1.43 (m, 6H), 0.97 (t, J = 7.3 Hz, 3H),
114.7, 85.0, 73.4, 70.3, 38.8, 36.7, 36.1, 35.2, 31.0, 20.1, 14.7, 0.95 (d, J = 6.8 Hz, 3H), 0.88 (d, J = 6.8 Hz, 3H), 0.84 (s, 9H),
14.6, 11.0. HRMS (ESI) m/z [M + Na]+: calcd for C25H33O5ClNa 0.05 (s, 3H), −0.04 (s, 3H); 13C NMR (CDCl3, 75 MHz):
471.1908, found 471.1912.
δ 200.0, 164.8, 150.9, 142.9, 141.2, 136.1, 130.9, 129.0,
(1E,3E,7S,8R,10R,11R,12R)-7-(tert-Butyldimethylsilyloxy)-12- 128.7, 127.2, 126.8, 120.9, 84.7, 73.7, 42.9, 36.7, 36.4,
ethyl-11-hydroxy-8,10-dimethyl-1-phenyltetradeca-1,3,13-trien- 35.7, 31.4, 25.8, 22.6, 17.9, 14.6, 13.3, 10.9, −4.7; HRMS (ESI)
5-one (32). Compound 32 (50 mg, 45% over four steps) was m/z calcd for C31H46O4NaSi [M + Na]+: 533.3630, found:
synthesized as a clear oil from 12b (91.0 mg, 0.71 mmol) and 533.3638.
aldehyde 24 (150 mg, 0.30 mmol) by following the same pro-
(5R,6R)-5-Ethyl-6-((2R,4R,5S,8E,10E)-5-hydroxy-4-methyl-7-
cedure as described for the synthesis of compound 30. Rf 0.27 oxo-11-phenylundeca-8,10-dien-2-yl)-5,6-dihydro-2H-pyran-2-
(SiO2, 10% EtOAc–hexanes); [α]2D5 = +42.61 (c 0.21, CHCl3); IR one (33). Compound 33 (9.5 mg, 88% yield) was synthesized
(neat): νmax 3400 (br), 2925, 2855, 1515, 1587, 1461, 1252, and as a clear oil from 9b (14 mg, 0.027 mmol) by following the
1
1066 cm−1; H NMR (CDCl3, 300 MHz): δ = 7.25–7.43 (m, 2H), same procedure as described for compound 31. Rf = 0.32 (SiO2,
7.41–7.27 (m, 4H), 7.01–6.82 (m, 2H), 6.30 (d, J = 15.5 Hz, 1H), 20% EtOAc–hexanes); [α]2D5 = −180 (c 0.14, CHCl3); IR (neat):
5.51 (ddd, J = 17.1, 10.4, 9.2 Hz, 1H), 5.09 (dd, J = 10.4, 2.0 Hz, νmax 3474(br), 2924, 2868, 1715, 1615, 1585, 1458, 1382, 1252
1H), 5.03 (dd, J = 10.4, 2.0 Hz, 1H) 4.14 (dt, J = 8.3, 3.7 Hz, 1H), and 1060 cm−1 1H NMR (CDCl3, 500 MHz): δ 7.51–7.43 (m,
;
3.28 (dd, J = 7.9, 3.7 Hz, 1H), 2.81 (dd, J = 14.5, 8.3 Hz, 1H), 2H), 7.42–7.28 (m, 4H), 7.05 (dd, J = 9.8, 6.8 Hz, 1H), 7.01 (d,
2.46 (dd, J = 14.5, 3.7 Hz, 1H), 2.06 (m, 1H), 1.85–1.58 (m, 6H), J = 15.7 Hz, 1H), 6.87 (dd, J = 14.7, 10.8 Hz, 1H), 6.27 (d, J =
0.91 (d, J = 6.8 Hz, 3H), 0.89–0.84 (m, 15H), 0.04 (s, 3H), −0.04 15.7 Hz, 1H), 6.04 (d, J = 9.8 Hz, 1H), 3.96 (dd, J = 10.8, 2.9 Hz,
(s, 3H); 13C NMR (CDCl3, 75 MHz) δ 200.0, 142.9, 141.3, 139.2, 1H), 3.92 (m, 1H), 2.82 (dd, J = 16.7, 2.0 Hz, 1H), 2.66 (dd, J =
136.0, 130.8, 129.1, 128.8, 127.2, 126.7, 116.4, 79.0, 74.1, 49.7, 16.7, 9.8 Hz, 1H), 2.34 (m, 1H), 1.95 (m, 1H), 1.84–1.66 (m,
43.8, 36.4, 32.7, 31.3, 25.8, 22.6, 18.0, 17.0, 13.8, 11.6, −4.6, 3H), 1.65–1.47 (m, 2H), 1.00 (t, J = 7.8 Hz, 3H), 0.95 (d, J =
−4.7; HRMS (ESI) m/z calcd for C30H48O3NaSi [M + Na]+: 5.9 Hz, 0.95 (d, J = 5.9 Hz, 3H), 0.91 (d, J = 5.9 Hz, 3H); 13C
507.3270, found: 507.3272.
NMR (CDCl3, 150 MHz): δ 201.7, 165.1, 151.3, 143.8, 142.3,
(3R,4R,5R,7R,8S,11E,13E)-8-(tert-Butyldimethylsilyloxy)-3- 135.8, 129.6, 129.4, 128.9, 127.4, 126.4, 121.0, 85.0, 72.3, 42.3,
ethyl-5,7-dimethyl-10-oxo-14-phenyltetradeca-1,11,13-trien-4-yl 36.7, 35.0, 31.2, 20.2, 14.5, 14.1, 13.7, 10.8; HRMS (ESI) m/z
acrylate (10b). Compound 10b (34 mg, 79% yield) was syn- calcd for C25H32O4Na [M + Na]+: 419.2198, found: 419.2197.
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 4002–4012 | 4011