O. Kraft, et al.
PhytochemistryLetters32(2019)29–32
55.0 (C–18), 48.7 (C–17), 48.3 (C–1), 48.2 (C–9), 42.8 (C–20), 42.6
(C–14), 40.8 (C–8), 40.2 (C–4), 38.9 (C–10), 38.9 (C–22), 33.9 (C–7),
29.7 (C–23), 29.7 (C–15), 27.5 (C–29), 27.3 (C–21), 26.8 (C–16), 25.1
(C–27), 24.5 (C–11), 19.4 (C–6), 18.0 (C–24), 17.7 (C–26), 17.3 (C–25),
17.2 (C–30) ppm; MS (ESI): m/z (%) = 487.3 ([M−H]−, 34), 532.9
([M+HCO2]−, 30), 975.4 ([2M−H]−, 100); analysis calculated for
C
30H48O5 (488.70): C 73.73, H 9.90; found: C 73.47, H 10.09.
Fig. 1. Structure of pomolic acid (1), euscaphic acid (2), and tormentic acid (3).
1.3. (2α,3β,19α) Benzyl 2,3,19-trihydroxyurs-12-en-28-oate (4)
To a solution of 3 (3.17 g, 6.48 mmol) in dry DMF (40 mL), dry,
freshly crushed potassium carbonate (1.0 g, 7.3 mmol) was added, the
mixture was stirred for 1 h, and benzyl bromide (0.92 mL, 7.75 mmol)
was added. After 24 h of stirring at room temperature followed by usual
work-up and chromatography (silica gel, CHCl3/Et2O/MeOH, 30:10:1)
4 (3.49 g, 93%) was obtained as a colorless solid; m.p. 115–117 °C (lit.:
1147vs, 1030vs, 998s, 968s, 931m, 752s, 696vs cm−1; UV–vis (CHCl3):
λmax (log ε) = 256 (4.05) nm; 1H NMR (400 MHz, CDCl3):
δ = 7.39–7.27 (m, 5H, 33–H + 35–H + 34–H), 5.36 (dd, 1H, J = 3.7,
3.7 Hz, 12–H), 5.08 (d, 1H, J = 12.5 Hz, 31–Ha), 4.99 (d, 1H,
J = 12.5 Hz, 31–Hb), 3.69 (ddd, 1H, J = 10.9, 10.8, 4.5 Hz, 2–H), 3.00
(d, 1H, J = 9.4 Hz, 3–H), 2.62 (s, 1H, 18–H), 2.58–2.47 (m, 1H, 16–Ha),
2.07–1.90 (m, 3H, 11–Ha + 11–Hb + 1–Ha), 1.80–1.44 (m, 8H, 22–Ha
+ 21–Ha + 15–Ha + 16–Hb + 9–H + 22–Hb + 6–Ha + 7–Ha),
1.44–1.17 (m, 4H, 20–H + 6–Hb + 7–Hb + 21–Hb), 1.26 (s, 3H, 27–H),
1.21 (s, 3H, 29–H), 1.07–0.89 (m, 2H, 15–Hb + 1–Hb), 1.03 (s, 3H,
23–H), 0.96 (s, 3H, 25–H), 0.94 (d, 3H, J = 6.6 Hz, 30–H), 0.87–0.84
(m, 1H, 5–H), 0.82 (s, 3H, 24–H), 0.61 (s, 3H, 26–H) ppm; 13C-NMR
(100 MHz, CDCl3): δ = 177.7 (C–28), 138.3 (C–13), 136.5 (C–32),
129.1 (C–12), 128.6 (C–33), 128.1(C–35), 128.1 (C–34), 84.1 (C–3)
73.3 (C–19), 69.1 (C–2), 66.3 (C–31), 55.3 (C–5), 53.4 (C–18), 48.2
(C–17), 47.3 (C–9), 46.6 (C–1), 41.4 (C–14), 41.2 (C–20), 40.2 (C–8),
39.3 (C–4), 38.4 (C–10), 37.5 (C–22), 32.9 (C–7), 28.8 (C–23), 28.3
(C–15), 27.6 (C–29), 26.1 (C–21), 25.6 (C–16), 24.6 (C–27), 23.9
(C–11), 18.6 (C–6), 16.9 (C–26), 16.9 (C–24), 16.7 (C–25), 16.3 (C–30)
ppm; MS (ESI): m/z (%) = 561.1 ([M+H–H2O]+, 88), 579.1 ([M
+H]+, 100), 596.1 ([M + NH4]+, 18), 601.4 ([M + Na]+, 52); ana-
lysis calcd for C37H54O5 (578.82): C 76.76, H 9.40; found: C 76.52, H
9.63.
Scheme 1. a) BnBr, K2CO3, DMF, 12 h, 25 °C, 93%; b) m-(CF3)BzCl, pyridine,
1 h, 25 °C, 93%; c) Mg(ClO4)2, 6, hν = 365 nm, 25 W, THF/water (9:1), 8 h,
25 °C, 67%; d) Pd/C (10%), H2 (75 bar), THF, 1 day, 25 °C, 92%.
route to pomolic acid (1).
1. Experimental
For instrumentation and isolation of 2 and 3 as well as for a de-
piction of the NMR spectra: cf. Supplementary material
1.1. (2α,3α,19α) 2,3,19-Trihydroxy-urs-12-en-28-oic acid (euscaphic
acid, 2)
formic acid, 30:10:1:0.2); MS (ESI): m/z (%) = 487.4 ([M−H]−, 100),
533.1 ([M+HCO2]−, 18), 555.2 ([M−H + NaHCO2]−, 30), 975.2
([2M−H]−, 44), 997.5 ([2M–2H + Na]−, 40).
1.4. (2α,3β,19α) Benzyl 3,19-dihydroxy-2-O-[m-(trifluoromethyl)
benzoyl]-urs-12-en-28-oate (5)
To a solution of 4 (1.5 g, 2.60 mmol) in dry pyridine (100 mL), m-
(trifluoromethyl)benzoyl chloride (0.5 mL, 3.1 mmol) was slowly
added, and stirring at 25 °C was continued for another 90 min. Usual
aqueous work-up followed by an extraction with diethyl ether and
chromatography (silica gel, n-hexane/ethyl acetate, 6:1) gave 5 (1.82 g,
93%) as a colorless solid; m.p. 108–112 °C; [α]D = −6.0° (c = 0.16,
CHCl3); RF = 0.64 (SiO2, n-hexane/ethyl acetate, 4:1); IR (ATR):
ν = 3532br, 2933w, 1716m, 1455w, 1379w, 1336s, 1303m, 1258vs,
1167s, 1129vs, 1072s, 1031m, 955m, 923m, 756s, 695vs cm−1; UV–vis
(CHCl3): λmax (log ε) = 237 nm (4.07); 1H NMR (400 MHz, CDCl3):
δ = 8.28 (d, 1H, J = 1.8 Hz, 42–H), 8.23 (ddd, 1H, J = 7.8, 1.4, 1.4 Hz,
41–H), 7.81 (ddd, 1H, J = 7.8, 2.0, 1.0 Hz, 40–H), 7.58 (dd, 1H,
J = 7.8, 7.8 Hz, 38–H), 7.40–7.28 (m, 5H, 33–H + 34–H + 35–H), 5.34
(dd, 1H, J = 3.7, 3.7 Hz, 12–H), 5.26 (ddd, 1H, J = 11.4, 9.9, 4.5 Hz,
2–H), 5.09 (d, 1H, J = 12.5 Hz, 31–Ha), 5.00 (d, 1H, J = 12.5 Hz,
31–Hb), 3.40 (d, 1H, J = 10.2 Hz, 3–H), 2.62 (s, 1H, 18–H), 2.53 (ddd,
1H, J = 13.1, 12.1, 4.5 Hz, 16–Ha), 2.12 (dd, 1H, J = 12.2, 4.6 Hz,
1–Ha), 2.02–1.88 (m, 2H, 11–Ha + 11–Hb), 1.81–1.48 (m, 8H, 6–Ha +
7–Ha + 21–Ha + 22–Ha + 15–Ha + 22–Hb + 16–Hb + 9–H),
1.47–1.35 (m, 2H, 6–Hb + 20–H), 1.33–1.21 (m, 2H, 7–Hb + 21–Hb),
1.2. (2α,3β,19α) 2,3,19-Trihydroxy-urs-12-en-28-oic-acid (tormentic
acid, 3)
δ = 5.57 (dd, 1H, J = 2.9, 2.9 Hz, H–12), 4.23 (ddd, 1H, J = 11.9, 9.7,
4.1 Hz, H–2), 3.42 (d, 1H, J = 9.0 Hz, H–3), 3.13 (ddd, 1H, J = 13.6,
12.5, 2.9 Hz, H–16a), 3.07 (s, 1H, H–18), 2.35 (ddd, 1H, J = 15.2, 14.2,
3.1 Hz, H–15a), 2.27 (dd, 1H, J = 12.0, 2.7 Hz, H–1a), 2.22–1.94 (m,
6H, H–9 + H–11a + H–11b + H–21a + H–22a + H–22b), 1.88–1.56
(m, 3H, H–6a + H–7a + H–16b), 1.71 (s, 3H, H–27), 1.54–1.37 (m, 3H,
H–6b + H–7b + H–20), 1.48 (s, 3H, H–29), 1.42–1.26 (m, 3H, H–1b +
H–15b + H–21b), 1.31 (s, 3H, H–23), 1.15–1.02 (m, 1H, H–5), 1.15 (d,
3 H, J = 6.8 Hz, H–30), 1.15 (s, 3H, H–25), 1.12 (s, 3H, H–24), 1.05 (s,
3H, H–26) ppm; 13C NMR (125 MHz, C5D5N): δ = 181.0 (C–28), 140.4
(C–13), 128.3 (C–12), 84.3 (C–3), 73.1 (C–19), 69.0 (C–2), 56.4 (C–5),
30