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residue was carefully chromatographed on silica eluting with n- solid) upon standing at 5 ꢂC: mp 113–115 ꢂC; [a]D24 +76.3 (c 1.0,
hexane–EtOAc (9 : 1) to give 245 mg (88% based on the D4(18)
-
DCM). 1H NMR (300 MHz) d 9.97 (1H, d, J ¼ 1.2), 7.18 (1H, d, J ¼
isomer in the alkenes 9 mixture) of epimeric aldehydes 7a,b 8.4), 7.02 (1H, dd, J ¼ 8.4, 2.1), 6.91 (1H, d, J ¼ 2.1), 3.96 (1H, d, J
(NMR data vide infra) as a colorless oil which were used in the ¼ 10.8), 3.56 (1H, d, J ¼ 10.8), 3.00–2.90 (2H, m), 2.83 (1H, sept.,
next step directly (aldol reaction).
J ¼ 6.9), 2.34 (2H, m), 2.40–1.60 (6H, m), 1.42 (1H, ddd, J ¼ 12.6,
18-Norabieta-8,11,13-trien-19-ol (13). To an ice-cold solution 12.1, 5.1), 1.23 (6H, d, J ¼ 6.9), 1.09 (3H, s); 13C NMR (75 MHz) dC
of alkenes 9 mixture (ca. 69%, 2.75 g, 10.8 mmol) in dry Et2O (60 205.9 (d), 146.1 (s), 144.8 (s), 134.2 (s), 126.9 (d), 124.8 (d), 124.1
mL) was added LiAlH4 (1.03 g, 27.0 mmol, 2.5 equiv.) and (d), 67.2 (t), 54.0 (s), 47.2 (d), 38.0 (t), 37.5 (s), 33.5 (d), 30.7 (t),
a solution of boron triuoride etherate (3.4 mL, 27.0 mmol, ca. 29.0 (t), 24.7 (q), 23.9 (q), 23.9 (q), 19.1 (t), 18.6 (t); HRMS (ESI)
2.5 equiv.) in dry Et2O (48 mL) during 20 min. Then, the mixture m/z 301.2170 [M + Na]+, calcd for C20H29O2: 301.2168.
was stirred for 4 h at rt, cooled at 0 ꢂC and treated with 5 mL of
When this procedure was rst carried out with the ca. 1 : 1
saturated Na2SO4 and some anhydrous solid Na2SO4. The solids mixture of aldehydes 7a,b, as starting material, we recovered
were ltered off and the diethyl ether layer was replaced by THF unreacted aldehyde 7b (19-norabieta-8,11,13-trien-18-al, Rf ¼
(90 mL) aer concentrating to leave a viscous colorless oil. The 0.50 in n-hexane–EtOAc (7 : 3)), which eluted prior to the aldol
resulting solution was treated with 10% aqueous NaOH (40 mL) product 6, as a semisolid: 1H NMR (300 MHz) d 9.54 (1H, d, J ¼
and 30% H2O2 (30 mL) and the biphasic mixture was stirred 4.5), 7.21 (1H, d, J ¼ 8.1), 7.01 (1H, br d, J ¼ 8.4), 6.91 (1H, d, J ¼
vigorously for 15 h. Aer this time, the reaction mixture was 2.1), 2.90–2.75 (3H, m), 1.23 (6H, d, J ¼ 6.9), 1.12 (3H, s); 13C
diluted with H2O (50 mL) and extracted with Et2O (3 ꢃ 30 mL). NMR (75 MHz) dC 205.2 (d), 146.1 (s), 144.4 (s), 134.6 (s), 127.1
The combined organic extracts were washed with brine, dried (d), 124.4 (d), 123.9 (d), 51.2 (d), 41.6 (d), 37.1 (t), 36.0 (s), 33.5
and concentrated. The resulting oily residue was chromato- (d), 29.0 (t), 26.4 (t), 24.0 (q), 24.0 (q), 23.0 (t), 22.7 (q), 20.6 (t).
graphed on silica eluting with n-hexane–EtOAc (6 : 4) to give
18-Hydroxyabieta-8,11,13-trien-19-oic acid (4, bodinieric
2.0 g (>95%) of 13 as a colorless oil: [a]2D5 +110.9 (c 1.0, DCM). acid B or callicapoic acid M4). To a stirred solution of aldol 6
The 1H NMR data were in agreement with those reported in the (500 mg, 1.67 mmol) and 2-methyl-2-butene (5 mL, 47.2 mmol)
literature:30 1H NMR (300 MHz) d 7.18 (1H, d, J ¼ 8.1), 7.01 (1H, in THF (5 mL) and tert-BuOH (16 mL) at rt was added NaClO2
dd, J ¼ 8.1, 2.1), 6.90 (1H, d, J ¼ 2.1), 3.75 (2H, m), 2.93–2.84 (3H, (80%, 1.20 g, 10.6 mmol, 6 equiv.) and NaH2PO4 (1.20 g,
m), 2.27 (1H, br d, J ¼ 11.5), 1.24 (6H, d, J ¼ 6.9), 1.06 (3H, s); 13
C
10.0 mmol, 6 equiv.) in H2O (7 mL). The reaction mixture was
NMR (75 MHz) dC 146.1 (s), 145.6 (s), 134.7 (s), 127.0 (d), 124.5 capped with a rubber septa with a needle as outlet and stirred
(d), 123.9 (d), 61.7 (t), 44.5 (d), 44.0 (d), 38.6 (t), 36.9 (s), 33.4 (d), for 4 h. Then, the solvent was removed under vacuum (bath
30.6 (t), 27.6 (t), 25.3 (t), 24.3 (q), 24.0 (q), 24.0 (q), 18.2 (t); HRMS temperature 40 ꢂC) and the resulting watery residue was diluted
(ESI) m/z 336.2343 [M + CH3CN + Na]+, calcd for C21H31NONa: with EtOAc (80 mL) and 10% HCl (40 mL) and brine (20 mL).
336.2303.
18-Norabieta-8,11,13-trien-19-al (7a).
The phases were separated and the aqueous layer was extracted
solution of the with EtOAc (3 ꢃ 20 mL) and the combined organic extracts were
A
alcohol 13 (2.0 g, 7.3 mmol) was dissolved in DCM (160 mL) and washed with brine (20 mL), dried and concentrated. The
treated with PCC (3.0 g, 13.9 mmol, 1.9 equiv.). Aer stirring for resulting pale oil was chromatographed on silica eluting with
2 h, the mixture was ltered through a short pad of silica eluting DCM–MeOH (9 : 1) to give 432 mg (82%) of acid 4 as an amor-
with DCM to afford the corresponding b-aldehyde 7a (1.93 g, phous white solid: [a]2D2 +104.9 (c 0.10, MeOH) (lit.,3a +57.3 (c
97%) as a yellowish oil which was used in the next step without 0.10, MeOH)) (lit.,3b +22.2 (c 0.10, MeOH)). The 1H and 13C NMR
further purication: [a]2D4 +178.0 (c 1.0, DCM). The 1H NMR data data were in agreement with those of the natural product in
were in agreement with those reported in the literature:7 1H both acetone-d6 (ref. 3a) and CDCl3 (ref. 3b): 1H NMR (300 MHz,
NMR (300 MHz) d 10.03 (1H, d, J ¼ 1.2), 7.18 (1H, d, J ¼ 8.1), 7.02 CD3COCD3) d 7.21 (1H, d, J ¼ 8.1), 6.97 (1H, dd, J ¼ 8.1, 2.1), 6.86
(1H, dd, J ¼ 8.1, 2.1), 6.93 (1H, d, J ¼ 2.1), 3.00–2.94 (2H, m), 2.84 (1H, d, J ¼ 2.1), 3.87 (1H, d, J ¼ 10.2), 3.66 (1H, d, J ¼ 10.2), 2.90–
(1H, sept., J ¼ 6.9), 1.24 (3H, d, J ¼ 6.9), 1.23 (3H, d, J ¼ 6.9), 1.04 2.70 (3H, m), 2.31 (2H, m), 1.78 (1H, m), 1.65 (1H, m), 1.19 (6H,
(3H, s); 13C NMR (75 MHz) dC 204.7 (d), 146.0 (s), 144.6 (s), 134.4 d, J ¼ 6.9), 1.15 (3H, s); 13C NMR (75 MHz, CD3COCD3) dC 177.4
(s), 127.1 (d), 124.8 (d), 124.1 (d), 52.3 (d), 45.0 (d), 38.1 (t), 37.5 (s), 146.7 (s), 146.3 (s), 135.7 (s), 127.5 (d), 126.2 (d), 124.6 (d),
(s), 33.5 (d), 30.8 (t), 24.8 (t), 24.2 (t), 24.0 (q), 24.0 (q), 23.7 (q), 70.2 (t), 50.6 (s), 47.5 (d), 40.1 (t), 38.8 (s), 34.3 (d), 32.5 (t), 32.3
19.1 (t); HRMS (ESI) m/z 293.1921 [M + Na]+, calcd for (t), 24.4 (q), 24.3 (q), 24.0 (q), 21.7 (t), 20.4 (t); 1H NMR (300 MHz,
C
19H26ONa: 293.1881.
CDCl3) d 7.18 (1H, d, J ¼ 8.1), 6.99 (1H, dd, J ¼ 8.4, 2.1), 6.89 (1H,
18-Hydroxyabieta-8,11,13-trien-19-al (6). A solution of the br s), 4.17 (1H, d, J ¼ 10.2), 3.50 (1H, d, J ¼ 10.8), 2.90–2.70 (3H,
aldehyde 7a (1.91 g, 7.0 mmol) was dissolved in a 1 : 1 MeOH– m), 2.45 (1H, br d, J ¼ 12.9), 2.29 (1H, br d, J ¼ 12.9), 2.10–2.00
DCM mixture (120 mL) and treated with excess 37% aqueous (3H, m), 1.72 (2H, m), 1.22 (6H, d, J ¼ 6.9), 1.15 (3H, s); 13C NMR
HCHO (25 mL, 0.336 mol, 48 equiv.) and Na2CO3 (400 mg, (75 MHz, CDCl3) dC 181.3 (s), 145.8 (s), 145.3 (s), 134.6 (s), 126.8
3.8 mmol, 0.54 equiv.) under an Ar atmosphere. Aer being (d), 125.3 (d), 124.0 (d), 71.4 (t), 49.9 (s), 47.7 (d), 38.9 (t), 38.1 (s),
stirred for 5 h, the mixture was diluted with DCM (120 mL) and 33.4 (d), 31.9 (t), 31.5 (t), 23.9 (q), 23.9 (q), 23.4 (q), 20.8 (t), 19.3
washed with a mixture of 30 mL of water and 30 mL of brine, (t); HRMS (ESI) m/z 317.2111 [M + H]+, calcd for C20H29O3:
dried and concentrated. The crude oily residue was chromato- 317.2117.
graphed on silica eluting with n-hexane–EtOAc (7 : 3) to give
17-Nor-18-hydroxy-15-oxoabieta-8,11,13-triene-19-oic acid (3,
1.5 g (70%) of aldol 6 as a colorless solid which solidied (white bodinieric acid A). A solution of hydroxyacid 4 (75 mg, 0.237
15020 | RSC Adv., 2020, 10, 15015–15022
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