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S. R. Doda et al.: Asymmetric total synthesis of filamentous fungi related resorcylic acid lactones 7-epi-zeaenol
obtained 7 (340 mg, 89%) as a colorless viscous liquid. [α] by silica gel column chromatography (acetone/hexane 1:1)
25 −1 7.6 ( c 1.0, CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.52 (d, J to obtain compound 2 (17.3 mg, 88%) as a white powder.
D
25
1
= 15.8 Hz, 1H), 7.41 – 7.22 (m, 10H), 6.70 (d, J = 2.7 Hz, 1H), [α]D −91 (c 1.5, MeOH); H NMR (500 MHz, DMSO-d6) δ
6.33 (d, J = 2.5 Hz, 1H), 6.25 (dt, J = 15.1, 7.1 Hz, 1H), 5.62 (dd, 10.57 (s, 1H), 6.62 (d, J = 15.5 Hz, 1H), 6.43 (d, J = 2.28 Hz,
J = 6.1, 3.7 Hz, 2H), 4.84 (d, J = 11.4 Hz, 1H), 4.77 – 4.70 (m, 1H), 6.30 (d, J = 2.27 Hz, 1H), 6.1 (m, 1H), 5.66-5.53 (m, 2H),
2H), 4.63 (d, J = 11.6 Hz, 1H), 4.58 (q, J = 5.9, 5.5 Hz, 1H), 5.19 (m, 1H), 4.82 (s, 1H), 4.80 (s, 1H), 4.50 (d, J = 4.1 Hz,
4.55 – 4.48 (m, 1H), 3.82 (s, 3H), 3.76 (m, 1H), 3.68 (d, J = 5.3 1H), 4.05 (m, 1H), 3.75 (s, 3H), 3.60 (m, 1H), 3.35 (m, 1H),
Hz, 2H), 3.36 (s, 3H), 2.72 (q, J = 7.5 Hz, 2H), 2.31 – 2.09 (m, 2.48-2.32 (m, 3H), 2.17 (m, 1H), 1.33 (d, J = 5.9 Hz, 3H) ppm;
2H), 1.70 (s, 6H), 1.17 (d, J = 6.4 Hz, 3H).; 13C NMR (75 MHz, 13C NMR (126 MHz, DMSO) δ 169.0, 161.7, 159.0, 139.6, 133.1,
CDCl3) δ 164.7, 160.0, 158.7, 144.0, 138.6, 138.3, 131.9, 131.4, 132.5, 128.6, 127.0, 110.3, 102.7, 99.9, 77.5, 74.7, 72.9, 71.8, 55.2,
130.3, 130.3, 128.3, 128.3, 128.2, 128.1, 128.0, 127.7, 127.6, 38.6, 36.8, 29.6, 20.4. HRMS (ESI): calcd. for C19H24O7Na [M
127.5, 108.3, 104.9, 100.4, 100.1, 93.9, 81.4, 78.5, 78.3, 73.9, + Na]+387.1415, found: 387.1419.
71.6, 67.0, 55.6, 42.1, 33.5, 25.7, 25.6, 22.8; HRMS (ESI): calcd.
(3S,5E,7R,8R,9S,11E)-8,9-Bis(benzyloxy)-7,16-dihy-
droxy-14-methoxy-3-methyl-3,4,7,8,9,10-hexahydro-
for C38H47O9 [M + H]+647.3215, found: 647.3211.
(3S,5E,7R,8S,9S,11E)-8,9-Bis(benzyloxy)-16- 1H-benzo[c][1]oxacyclotetradecin-1-one (19): TMSCl
hydroxy-14-methoxy-7-(methoxymethoxy)-3- (0.056 mL, 0.45 mmol) was added to stirred solution of
methyl-3,4,7,8,9,10-hexahydro-1H-benzo[c][1] 18 (0.175 mg, 0.297 mmol) in MeOH (5 mL) and allowed
oxacyclotetradecin-1-one (18): To a suspension of NaH to stir for 2 hrs at room temperature. After completion
(0.15 g, 3.7 mmol) washed with hexane twice to remove of the reaction as indicated by TLC, the methanol was
mineral oil and dried in dry THF (10 mL) was added a removed and the residue was dissolved in a saturated
solution of alcohol 7 (0.3 g, 0.46 mmol) in THF (5 mL) at solution of NaHCO3 (10 mL) then extracted with ethyl
o
0 C under argon and the suspension was stirred for 5 h acetate (3 x 15 mL), dried over anhydrous Na2SO4 and con-
at room temperature. After completion of the reaction centrated under reduced pressure and then purified by
(monitored by TLC), the reaction mixture was quenched silica gel column chromatography (ethyl acetate/hexane
25
with ice pieces at 0 oC and extracted with ethyl acetate (3 x = 1:3) to give 19 (134 mg, 86%) as a colorless liquid. [α]D
1
10 mL). The combined organic layer was dried over anhyd- −76.0 (c 1.1, CHCl3) H NMR (500 MHz, C3D6O-d6): 7.48-7.16
rous Na2SO4 and solvent was removed under reduced pres- (m, 11H), 6.46 (s, 1H), 6.39 (s, 1H), 5.99 (m, 1H), 5.89 (m,
sure and purified by silica gel column chromatography 1H), 5.72 (m, 1H), 5.21 (m, 1H), 4.87-4.61 (m, 4H), 4.57 (m,
(ethyl acetate/hexane = 1:9) to afford 18 (0.27 mg, 85%) 1H), 4.27 (m, 1H), 3.91-3.82 (m, 4H), 2.79 (m, 1H), 2.64-2.57
as a colorless liquid. [α]D25 −55.8 (c 1.2, CHCl3) 1H NMR (500 (m, 3H), 1.43 (d, J = 5.9 Hz, 3H) ppm; 13C NMR (126 MHz,
MHz, CDCl3) δ 7.31 – 7.17 (m, 10H), 7.09 (d, J = 15.4 Hz, 1H), CDCl3 ) δ 171.6, 165.1, 164.2, 143.6, 138.9, 128.1, 128.0, 127.7,
6.38 (d, J = 2.5 Hz, 1H), 6.35 (d, J = 2.5 Hz, 1H), 5.89 (s, 1H), 127.5, 127.2, 106.8, 104.0, 99.7, 83.3, 78.3, 73.2, 55.0, 38.2,
5.79 (dd, J = 15.6, 9.3 Hz, 1H), 5.61 (ddd, J = 15.6, 8.1, 3.5 Hz, 19.5.HRMS (ESI): calcd. for C33H37O7 [M + H]+ 545.2534,
1H), 5.16 – 5.07 (m, 1H), 4.76 (d, J = 33.0 Hz, 2H), 4.62 (t, J found: 545.2541.
= 10.3 Hz, 1H), 4.47 (dd, J = 22.5, 8.9 Hz, 3H), 4.01 (m, 1H),
(3S,5E,7S,8R,9S,11E)-8,9-Bis(benzyloxy)-7,16-di-
3.92 (m, 3H), 3.81 (s, 3H), 3.32 (s, 3H), 2.70 (dt, J = 18.5, 9.3 hydroxy-14-methoxy-3-methyl-3,4,7,8,9,10-hexahy-
Hz, 1H), 2.65 – 2.53 (m, 3H), 2.44 – 2.27 (m, 1H), 1.42 (d, J = dro-1H-benzo[c][1]oxacyclotetradecin-1-one (20):
A
6.0 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 171.7, 165.0, 164.0, solution of alcohol 19 (0.12 g, 0.22 mmol), p-nitrobenzoic
143.6, 139.0, 133.3, 132.3, 128.4, 128.2, 127.8, 127.6, 127.6, acid (73 mg,0.44 mmol), and TPP (86 mg, 0.33 mmol) in THF
127.3, 107.4, 99.8, 92.8, 83.6, 81.3, 78.5, 73.4, 73.2, 71.9, 55.4, (15 mL) at 0 °C were treated with diisopropyl azodicarbo-
55.3, 38.7, 35.0, 29.7, 20.5; HRMS (ESI): calcd. for C35H41O8 [M xylate (66.6 g, 0.33 mmol) and the contents were stirred at
+ H]+589.2878, found: 589.2881.
0 °C for 1 hr and then at RT for 12 h. After completion of the
7-epi-zeaenol (2): TiCl4 (1.1 mL, 1.1 mmol, 1 M in reaction, the reaction mixture was concentrated, and the
CH2Cl2) was added to a stirred solution of 18 (35 mg, 0.06 resulting crude material was dissolved in ethyl acetate (60
mmol) in CH2Cl2 (5 mL) at 0 °C, and the mixture was stirred mL), and subsequently washed with the aqueous NaHCO3
for 1 hr for 30 min at 0 oC. After completion of the reaction (30 mL), water (50 mL), dried over Na2SO4 and concentra-
(monitored by TLC), the reaction mixture was quenched ted under vacuum. Purification of the residue by silica gel
with a saturated solution of NaHCO3 (10 mL), extracted column chromatography (25% EtOAc in hexanes) yielded
with CH2Cl2 (3 x 25 mL) and washed with brine (20 mL). The an ester which is not stable and immediately used in the
organic layer was dried over anhydrous Na2SO4 and con- next step. To a solution of above ester (0.22 mmol) in MeOH
centrated to afford a yellowish liquid, which was purified (5 mL) was added KOH (24 mg, 0.44 mmol) and the reaction
Unauthenticated
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