Convenient and chromatography-free partial syntheses of maslinic acid and augustic acid

Article abstract of DOI:10.1016/j.tetlet.2014.07.074

A convenient and chromatography-free 4-step synthesis of analytically pure maslinic acid (1, 41.2%) from oleanolic acid has been developed. Slight variations in the final steps gave an excellent yield of isomeric augustic acid (7, 71.9%).

Full text of DOI:10.1016/j.tetlet.2014.07.074

Tetrahedron Letters 55 (2014) 5156–5158
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Convenient and chromatography-free partial syntheses of maslinic
acid and augustic acid
⇑
Sven Sommerwerk, René Csuk
Martin-Luther-Universität Halle-Wittenberg, Organische Chemie, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
A convenient and chromatography-free 4-step synthesis of analytically pure maslinic acid (1, 41.2%) from
oleanolic acid has been developed. Slight variations in the final steps gave an excellent yield of isomeric
augustic acid (7, 71.9%).
Received 27 May 2014
Revised 20 July 2014
Accepted 21 July 2014
Available online 24 July 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Triterpenes
Maslinic acid
Augustic acid
Oleanolic acid
Synthesis
Cancer is one of the leading causes of death in Western people,
second to heart diseases. Lung and bronchial cancer is still the top
killer cancer in the USA, followed by colon and rectal cancer,
breast, pancreatic, and prostate cancer. According1 to a WHO prog-
nosis, deaths from cancer worldwide are projected to continue ris-
ing, with an estimated 13.1 million deaths in 2030. Treatment of
cancer requires a careful selection of intervention such as radio-
therapy, surgery, or chemotherapy to cure the disease or consider-
ably prolong life while improving the patient’s quality. Plants
provide a broad spectrum of potential drug substances2 for chemo-
therapy of life. Pentacyclic triterpenes3 of the ursane, lupane, and
oleanane series are one group of promising secondary plant
metabolites.
Quite recently, maslinic acid (1, Fig. 1) and several of its deriv-
atives4–6 have been identified as new and very promising com-
pounds, and their role in the cancer setting is gradually
emerging. This led to an increased need in larger amounts of 1.
Starting with its first isolation from the leaves of Hawthorne
(Crataegus oxyacantha L.) by Bächler7 in 1927, many different
plants have been screened as potential sources for obtaining 1. A
major breakthrough (albeit almost forgotten) was the extraction
of 1 from olive cake8 by L. Caglioti in 1960. Improvements of this
technique9–12 allowed the isolation of 1 in significant amounts.
Since this pomace is readily available only in countries growing
olives, the isolation of 1 from edible green or black olives has been
suggested13 as an alternative. Both procedures13 gave yields
between 0.25% (pomace) and 0.36% (olives).
Recently, we synthesized14 several derivatives exhibiting cyto-
toxic effects; one of these compounds (‘EM2’, a diacetylated ben-
zylamide)13 exhibited a very high cytotoxicity for human ovarian
cancer cells (IC50 = 0.5
lM) whereas the cytotoxicity for non-
malignant human fibroblasts (IC50 = 156
l
M) was low. During
planning of extended testing of EM2 in tumor bearing animals, a
large amount of 1 was needed—and its isolation from olives using
typical lab-equipment ran into major problems. Known syntheses
of 115–17 were difficult to reproduce on a larger scale—and each
of them involved extensive chromatographic work-up procedures.
Hence, we decided to develop a synthesis of 1 using an inexpensive
starting material18 using only a few steps and avoiding chromato-
graphic work-up.
Thus, commercially available and inexpensive oleanolic acid
(2)18 was oxidized at position C-3 by the Jones oxidation in the
presence of silica gel,19,20 and an almost quantitative yield of
⇑
Corresponding author. Tel.: +49 (0) 345 5525660; fax: +49 (0) 345 5527030.
E-mail address: rene.csuk@chemie.uni-halle.de (R. Csuk).
Figure 1. Structure of maslinic acid (1) and oleanolic acid (2).
http://dx.doi.org/10.1016/j.tetlet.2014.07.074
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

S. Sommerwerk, R. Csuk / Tetrahedron Letters 55 (2014) 5156–5158
5157
Scheme 1. Synthesis of maslinic acid (1) and augustic acid (7) from oleanolic acid (2): (a) CrO3/H2SO4, silica gel, 0 °C; (b) pyridinium tribromide, acetic acid, 25 °C, 180 min;
(c) NaOH (2 equiv), DMF, 0 °C, 30 min; (d) air, NaOH (5 equiv), DMF, 60 °C, 1 h; (e) NaBH4, 0 °C, 1 h, then acetone/H2SO4, 30 min, 0 °C, recryst. from ethyl acetate, 41.2% (over-
all); (f) NaBH4, 0 °C, 1 h, recryst. from ethyl acetate, 71.9% (over-all).
slightly yellowish 321 was obtained, whose reaction with pyridini-
8. Caglioti, L.; Cainelli, G.; Minutilli, F. Atti Accad. Nazl. Lincei, Rend., Classe Sci., Fis. e
Mat. 1960, 29, 544–548.
um tribromide in acetic acid22,23 furnished a mixture of bromides
9. Garcia-Granados Lopez De Hierro, A., WO9804331A1; Chem. Abstr. 1998,
4.24 Reaction of 4 with sodium hydroxide in DMF24 at 0 °C for
98357.
30 min gave hydroxylated 522,25 whose reduction with NaBH4 at
10. Romero, C.; García, A.; Medina, E.; Ruíz-Méndez, M. V.; Castro, A. D.; Brenes, M.
Food Chem. 2010, 118, 670–674.
11. Parra, A.; Martin-Fonseca, S.; Rivas, F.; Reyes-Zurita, F. J.; Medina-O’Donnell,
0 °C26 yielded the title compound 1 (together with some 3-epi-
maslinic acid;27 ratio maslinic acid/3-epi-maslinic acid = 4:1).
M.; Martinez, A.; Garcia-Granados, A.; Lupianez, J. A.; Albericio, F. Eur. J. Med.
Chem. 2014, 74, 278–301.
12. Guinda, A.; Rada, M.; Delgado, T.; Gutierrez-Adamez, P.; Castellano, J. M. J.
Agric. Food Chem. 2010, 58, 9685–9691.
13. Siewert, B.; Pianowski, E.; Obernauer, A.; Csuk, R. Bioorg. Med. Chem. 2014, 22,
594–615.
14. Siewert, B.; Pianowski, E.; Csuk, R. Eur. J. Med. Chem. 2013, 70, 259–272.
15. Caglioti, L.; Cainelli, G. Tetrahedron 1962, 18, 1061–1062.
16. Wang, X.; Shi, C.; Huang, Y.; Chen, J.; Jiang, X.; Ding, P.; Ding, H.; Gong, Z.
CN101974064A; Chem. Abstr. 2011, 217562.
17. Sun, H.; Wen, X.; Ni, P. CN1634971A; Chem. Abstr. 2006, 53493.
18. Csuk, R.; Siewert, B. Tetrahedron Lett. 2011, 52, 6616–6618. In addition,
oleanolic acid can be obtained from several suppliers in bulk quantities.
19. Thus, treatment of 2 with oxoneÒ led to the formation of a 3,4-seco-olean
Thus, analytically pure 1 was obtained after only one re-crystalliza-
tion from ethyl acetate in a 4-step procedure with an over-all yield
of 41.2% (from oleanolic acid). Reaction of 4 with air and excess of
sodium hydroxide in DMF at 60 °C for an hour, however, yielded
enol 6.28 To our surprise this reaction proceeded quite smoothly
and in almost quantitative yield. Previously, similar transforma-
tions have been carried out either by microbial transformations29
or by microwave-assisted30 syntheses. Reduction of 6 with NaBH4
at 0 °C gave an excellent yield of augustic acid (7)31 (Scheme 1).
This synthetic approach can easily be scaled up and allows the
preparation of 1 in large amounts. Simple re-crystallization fur-
nishes 1 of superior purity as determined by HPLC.32
derivative instead of an
a-hydroxylation. The procedure reported by Wang
et al. (Ref. 17) failed to give good yields in our hands and needed extensive
chromatographic work-up.
20. The addition of silica gel allows a more convenient work-up; for a silica gel
supported Jones oxidation: Ali, M. H.; Wiggin, C. J. Synth. Commun. 2001, 31,
1389–1397.
Acknowledgment
21. Typical procedure for the synthesis of 3: A suspension of 2 (19.72 g, 43.18 mmol)
and silica gel (150 mL) in acetone (1 L) was heated under reflux for 30 min.
After cooling to 0 °C Jones reagent [prepared from CrO3 (5.18 g, 51.82 mmol),
water (16.8 mL), and concd H2SO4 (5 mL)] were slowly added, and the mixture
was stirred for 30 min at 0 °C. Then MeOH (4 mL) was added, and stirring was
continued for another 30 min. The solvents were removed under diminished
pressure, and the resulting solid was extracted with ether (Soxhlet apparatus,
We like to thank Boehringer Ingelheim GmbH for a generous
donation of an ursolic/oleanolic acid mixture, Dr. D. Ströhl for the
NMR spectra, Dr. R. Kluge for the MS spectra and Ms J. Wiese for
measuring IR spectra and optical rotations. Many thanks are due
to Mr I. Serbian for his skillful help in the lab.
6 h). Evaporation of the ether furnished
3 (19.31 g, 98.4%) as a slightly
yellowish solid; an analytical sample showed mp: 225–227 °C (lit.: 226–229 °C
[An, R. -B. Nat. Prod. Sci. 2008, 14, 249–253]).
References and notes
22. Qiu, W. W.; Shen, Q.; Yang, F.; Wang, B.; Zou, H.; Li, J. Y.; Li, J.; Tang, J. Bioorg.
Med. Chem. Lett. 2009, 19, 6618–6622.
23. Ihara, M.; Toyota, M.; Fukumoto, K.; Kametani, T. J. Chem. Soc., Perkin Trans. 1
1986, 2151–2161.
1. Cancer. Available online at http://www.who.int/mediacentre/factsheets/fs297/
en/ (accessed 23.05.2014).
2. Chabner, B. A. Nat. Cancer Rev. 2005, 5, 65–72.
24. Typical procedure for the synthesis of 4: To a solution of crude 3 (19.25 g,
42.34 mmol) in acetic acid (500 mL), pyridinium tribromide (90%, 15.35 g,
43.18 mmol) was added at 25 °C within 60 min in several portions, and the
mixture was stirred for 2 h. After cooling (0 °C), water (1.5 L) was added, the
solid was filtered off and thoroughly washed with water, finally dried (CaCl2)
and 4 (22.57 g, quant.) was obtained as an off-white solid as a mixture of
epimers; for analysis the epimeric bromides were separated by
3. Pentacyclic Triterpenes as Promising Agents in Cancer; Salvador, J. A. R., Ed.; Nova
Science Publishers: New York, 2010.
4. Sanchez-Gonzalez, M.; Lozano-Mena, G.; Juan, M. E.; Garcia-Granados, A.;
Planas, J. M. Mol. Nutr. Food Res. 2013, 57, 339–346.
5. Siewert, B.; Csuk, R. Eur. J. Med. Chem. 2014, 74, 1–6.
6. Siewert, B.; Wiemann, J.; Köwitsch, A.; Csuk, R. Eur. J. Med. Chem. 2014, 72, 84–
101.
chromatography: (2
mp 149–158; Rf = 0.15 (silica gel, hexane/ethyl acetate, 8:2); [
a
)-2-bromo-3-oxoolean-12-en-28-oic acid: colorless solid,
+43.88° (c
7. Bächler, L. ‘Chemische Untersuchungen über die Früchte von Crataegus
Oxyacabtha L. (Monographie der Mehlbeeren)’, Dissertation, Univ. Basel, 1927.
a
]
D

5158
S. Sommerwerk, R. Csuk / Tetrahedron Letters 55 (2014) 5156–5158
0.35, CHCl3); IR (KBr):
1365m, 1305w, 1270m, 1187m, 1163m, 1065m, 1012m, 763s, 727m, 646s,
603s cmÀ1 1H NMR (500 MHz, CDCl3): d = 5.28 (dd, J = 3.6, 3.6 Hz, 1H, CH (12)),
m
= 3422v, 2949s, 2866s, 1724s, 1697s, 1461s, 1387s,
(24)), 0.93 (s, 3H, CH3 (29)), 0.93 (s, 3H, CH3 (30)), 0.81 (s, 3H, CH3 (26)) ppm;
13C NMR (126 MHz, CDCl3): d = 216.7 (C@O, C3), 183.9 (C@O, C28), 143.9
(C@CH, C13), 122.3 (CH@C, C12), 69.3 (CH, C2), 57.8 (CH, C5), 49.5 (CH2, C1),
;
5.06 (dd, J = 13.4, 6.1 Hz, 1H, CH (2)), 2.82 (dd, J = 13.8, 4.3 Hz, 1H, CH (18)),
2.56 (dd, J = 13.0, 6.1 Hz, 1H, CHa (1)), 2.14–1.88 (m, 4H, CHb (1)+CHa (16)+CHa
(11)+CHb (11)), 1.88–1.54 (m, 8H, CH (5)+CH (9)+CHa (19)+CHa (7)+CHb (7)+CHa
(15)+CHa (16)+CHb (16)), 1.54–1.40 (m, 3H, CHa (6)+CHb (6)+CHa (22)), 1.39–
1.01 (m, 6H, CH (2)+CHb (19)+CHb (22)+CHa (21)+CHb (21)+CHb (15)), 1.21 (s,
3H, CH3 (25)), 1.20 (s, 3H, CH3 (27)), 1.12 (s, 3H, CH3 (23)), 1.09 (s, 3H, CH3
(24)), 0.93 (s, 3H, CH3 (29)), 0.90 (s, 3H, CH3 (30)), 0.80 (s, 3H, CH3 (26)) ppm;
13C NMR (126 MHz, CDCl3): d = 206.9 (C@O, C3), 184.3 (C@O, C28), 144.0
(C@CH, C13), 122.0 (CH@C, C12), 56.7 (CH, C2), 52.4 (CH2, C1), 52.3 (CH, C5),
47.9 (Cquart, C4), 47.5 (CH, C9), 46.6 (Cquart, C17), 45.9 (CH2, C19), 41.8 (Cquart,
C14), 41.1 (CH, C18), 39.6 (Cquart, C8), 37.9 (Cquart, C10), 33.9 (CH2, C21), 33.2
(CH3, C30), 32.6 (CH2, C7), 32,5 (CH2, C22), 30.8 (Cquart, C20), 27.8 (CH2, C15),
26.1 (CH3, C27), 24.9 (CH3, C23), 23.8 (CH3, C29), 23.7 (CH2, C11), 23.0 (CH2,
C16), 21.7 (CH3, C24), 19.3 (CH2, C6), 17.4 (CH3, C26), 16.2 (CH3, C25) ppm; MS
(ESI): m/z (%) = 469.5 ([MÀH]À, 100), 939.2 ([2MÀH]À, 66), 961.7
([2MÀ2H+Na]À, 28); analysis calcd for C30H46O4 (470.68): C 76.55, H 9.85;
found: C 76.21, H 9.98..
26. Wen, X.; Sun, H.; Liu, J.; Cheng, K.; Zhang, P.; Zhang, L.; Hao, J.; Zhang, L.; Ni, P.;
Zographos, S. E.; Leonidas, D. D.; Alexacou, K.-M.; Gimisis, T.; Hayes, J. M.;
Oikonomakos, N. G. J. Med. Chem. 2008, 51, 3540–3554.
27. Typical procedure for the synthesis of 1: To a solution of crude 5 (19.8 g,
42.28 mmol) in THF (200 mL) and MeOH (40 mL), NaBH4 (0.8 g, 21.14 mmol)
was added at 0 °C. The mixture was stirred at 0 °C for 60 min, HCl (aq, 2 M,
20 mL) and water (1.5 L) were added, and the precipitate was collected and
49.5 (Cquart, C4), 47.1 (CH, C9), 46.7 (Cquart, C17), 45.9 (CH2, C19), 41.9 (Cquart
,
C14), 41.1 (CH, C18), 40.0 (Cquart, C8), 39.5 (Cquart, C10), 33.9 (CH2, C21), 33.2
(CH3, C30), 32.5 (CH2, C7), 32,3 (CH2, C22), 30.8 (Cquart, C20), 27.8 (CH2, C15),
26.5 (CH3, C27), 26.0 (CH3, C23), 23.7 (CH3, C29), 23.6 (CH2, C11), 22.8 (CH2,
C16), 22.1 (CH3, C24), 19.4 (CH2, C6), 17.3 (CH3, C26), 15.4 (CH3, C25) ppm; MS
(ESI): m/z (%) = 531.3 ([C30H4579BrO3ÀH]À, 48), 533.3 ([C30H4581BrO3ÀH]À, 52),
1063.1 ([2C30H4579BrO3ÀH]À, 92), 1065.1 ([C30H4579BrO3+C30H4581BrO3ÀH]À,
100); analysis calcd for C30H45BrO3 (533.58): C 67.53, H 8.50; found: C 67.27, H
8.71. (2b)-2-Bromo-3-oxoolean-12-en-28-oic acid: colorless solid; mp 146–
dried. The crude mixture (consisting of
1 and 3-epi-maslinic acid) was
dissolved in acetone (200 mL) at 60 °C, then cooled (0 °C), and a solution of
concd H2SO4 (6 mL) in acetone (100 mL) (according to Tschesche, R., Henckel,
E., Snatzke, G. Liebigs Ann. Chem. 1964, 676, 175–187) was added. After stirring
for 30 min, water (1.5 L) was added and the solid was collected and dried. Re-
crystallization from ethyl acetate furnished 1 (8.41 g, 41.2%) as a colorless
solid; mp: 266–270 °C (decomp.) (lit.: 269–271 °C Ref. 26). Workup of the
151 °C; Rf = 0.22 (silica gel, hexane/ethyl acetate 8:2); [
CHCl3); IR (KBr): = 3425 m, 2949s, 1731s, 1697s, 1636w, 1459s, 1388s,
1365 m, 1305 m, 1268 m, 1208 m, 1162 m, 1062 m, 774s, 709 m, 646 m,
606 m cmÀ1 1H NMR (500 MHz, CDCl3): d = 5.30 (dd, J = 3.4, 3.4 Hz, 1H, CH
a] +120.03° (c 0.25,
D
m
;
(12)), 5.08 (dd, J = 11.0, 9.5 Hz, 1H, CH (2)), 2.84 (dd, J = 13.9, 3.9 Hz, 1H, CH
(18)), 2.50 (dd, J = 13.6, 11.3 Hz, 1H, CHa (1)), 2.10–1.91 (m, 3H, CHa (11)+CHa
(16)+CHb (1)), 1.92–1.44 (m, 10H, CHb (16)+CH (5)+CH (9)+CHa (22)+CHb
(22)+CHa (15)+CHa (19)+CHb (11)+CHa (7)+CHa (6)), 1.44–1.30 (m, 3H, CHb
(6)+CHb (7)+CHa (21)), 1.30–1.02 (m, 3H, CHb (21)+CHb (19)+CHb (15)), 1.17 (s,
3H, CH3 (27)), 1.14 (s, 3H, CH3 (23)), 1.13 (s, 3H, CH3 (29)), 0.93 (s, 3H, CH3
(24)), 0.91 (s, 3H, CH3 (30)), 0.88 (s, 3H, CH3 (25)), 0.76 (s, 3H, CH3 (26)) ppm;
13C NMR (126 MHz, CDCl3): d = 209.2 (C@O, C3), 183.1 (C@O, C28), 143.6
(C@CH, C13), 122.4 (CH@C, C12), 53.5 (CH2, C1), 52.7 (CH, C5), 51.2 (CH, C2),
mother liquor furnished the (2a,3a) acetonide of 3-epi-maslinic acid (Muthuk-
uda, P. M. Chem. Sri Lanka 1985, 2, 13–15) whose acidic hydrolysis (aqueous
H2SO4) furnished known 3-epi-maslinic acid (2.4 g, 12%, over all yield); mp
294–296 °C (lit.: 295–297 °C [Ref. 26].
28. Li, J.-F.; Zhao, Y.; Cai, M. M.; Li, X.-F.; Li, J.-X. Eur. J. Med. Chem. 2009, 44, 2796–
2806. Similarly, in the betulin series from the treatment of
with sodium azide and catalytic amounts of sodium iodide followed by a
thermal decomposition of an -azido ketone intermediate an enamine was
a-bromo ketones
a
obtained (cf. Ref. 25). An analytical sample of 2-hydroxy-3-oxoolean-1,12-
47.7 (Cquart, C4), 46.9 (CH, C9), 46.8 (Cquart, C17), 45.9 (CH2, C19), 42.1 (Cquart
,
dien-28-oic acid (6) showed: colorless solid; mp 137–141 °C; Rf = 0.50 (silica
C14), 41.4 (CH, C18), 39.6 (Cquart, C8), 39.3 (Cquart, C10), 34.0 (CH2, C21), 33.2
(CH3, C30), 32.5 (CH2, C22), 31,7 (CH2, C7), 30.8 (Cquart, C20), 29.6 (CH3, C23),
27.8 (CH2, C15), 25.9 (CH3, C27), 23.7 (CH3, C29), 23.6 (CH2, C11), 23.1 (CH2,
C16), 20.4 (CH3, C24), 20.1 (CH2, C6), 18.3 (CH3, C25), 16.6 (CH3, C26) ppm; MS
(ESI): m/z (%) = 531.3 ([C30H4579BrO3ÀH]À, 100), 533.3 ([C30H4581BrO3ÀH]À,
gel, hexane/ethyl acetate 6:4); [
kmax (log ) = 272 nm (4.31); IR (KBr):
1463s, 1429m, 1396s, 1385s, 1234m, 1149m, 1123s, 1056s, 803m, 458s cmÀ1
a] +100.97 (c 0.31, CHCl3); UV–vis (CHCl3):
D
e
m = 3441s, 2947s, 1713s, 1697s, 1652m,
;
1H NMR (500 MHz, CDCl3): d = 6.34 (s, 1H, CH (1)), 5.94 (s, 1H, OH (2)), 5.34 (dd,
J = 3.6, 3.6 Hz, 1H, CH (12)), 2.85 (dd, J = 13.7, 4.3 Hz, 1H, CH (18)), 2.20–1.92
(m, 3H, CHa (16)+CHa (11)+CHb (11)), 1.91–1.85 (m, 1H, CH (9)), 1.84–1.67 (m,
2H, CHa (15)+CHa (22)), 1.67–1.43 (m, 6H, CHa (6)+CHb (16)+CHb (22)+CHa
(7)+CHa (19)+CH (5)), 1.43–1.06 (m, 6H, CHb (6)+CHb (15)+CHb (7)+CHa
(21)+CHb (21)+CHb (19)), 1.22 (s, 3H, CH3 (26)), 1.22 (s, 3H, CH3 (23)), 1.13
(s, 3H, CH3 (27)), 1.10 (s, 3H, CH3 (24)), 0.94 (s, 3H, CH3 (29)), 0.91 (s, 3H, CH3
(30)), 0.83 (s, 3H, CH3 (25)) ppm; 13C NMR (126 MHz, CDCl3): d = 201.2 (C@O,
C3), 183.5 (C@O, C28), 144.0 (C@CH, C2), 143.9 (C@CH, C13), 128.3 (CH@C, C1),
92),
1063.1
([2C30H4579BrO3ÀH]À,
54),
1065.1
([C30H4579BrO3+
C
30H4581BrO3ÀH]À, 60); analysis calcd for C30H45BrO3 (533.58): C 67.53, H
8.50; found: C 67.32, H 8.79.
25.
A similar transformation has been described very recently for a betulin
derivative: Pettit, G. R.; Noelean, M.; Hempenstall, F.; Chapuis, J.-C.; Groy, T. L.;
Williams, L. J. Nat. Prod. 2014, 77, 863–872. Typical procedure for our synthesis of
5: To a solution of crude 4 (22.56 g, 42.28 mmol) in DMF (200 mL), an aqueous
solution of NaOH (2 M, 44.4 mL, 88.78 mmol) was added at 0 °C. The mixture
was stirred for 30 min. The suspension was re-dissolved by the addition of
MeOH (250 mL), acidified (2 M HCl, 25 mL), and water (1.5 L) was added. The
precipitate was filtered off, washed, and dried to yield (2a)-2-hydroxy-3-
oxoolean-12-en-28-oic acid (5) (19.9 g, quant.) as an off-white solid; an
analytical sample showed: mp 143–146 °C; Rf = 0.41 (silica gel, hexane/ethyl
122.2 (CH@C, C12), 54.0 (CH, C5), 46.7 (Cquart, C4), 45.8 (CH2, C19), 44.0 (Cquart
,
C17), 43.2 (CH, C9), 42.1 (Cquart, C14), 41.3 (CH, C18), 40.1 (Cquart, C8), 38.6
(Cquart, C10), 34.0 (CH2, C21), 33.2 (CH3, C30), 32.6 (CH2, C7), 32,5 (CH2, C22),
30.8 (Cquart, C20), 27.8 (CH2, C15), 27.4 (CH3, C23), 26.0 (CH3, C27), 23.7 (CH3,
C29), 23.6 (CH2, C11), 23.0 (CH2, C16), 21.9 (CH3, C24), 19.3 (CH3, C26), 18.8
(CH2, C6), 17.7 (CH3, C25) ppm; MS (ESI): m/z (%) = 467.3 ([MÀH]À, 54), 935.3
([2MÀH]À, 28), 958.6 ([2MÀ2H+Na]À, 24); analysis calcd for C30H44BO4
(468.67): C 76.88, H 9.46; found: C 76.52, H 9.71.
acetate, 6:4); [
1636m, 1559w, 1540w, 1507w, 1458m, 1388s, 1268m, 1162m, 1101m,
1056m, 1029s, 994m, 646m cmÀ1 1H NMR (500 MHz, CDCl3): d = 5.28 (dd,
a] +64.23° (c 0.35, CHCl3); IR (KBr): m = 3446v, 2944s, 1700s,
D
;
29. Utsukihara, T.; Okada, S.; Kato, N.; Horiuchi, C. A. J. Mol. Catal. B: Enzym. 2007,
45, 68–72.
30. Utsukihara, T.; Nakamura, H.; Watanabe, M.; Horiuchi, C. A. Tetrahedron Lett.
2006, 47, 9359–9364.
J = 3.6, 3.6 Hz, 1H, CH (12)), 4.54 (dd, J = 12.6, 6.6 Hz, 1H, CH (2)), 2.83 (dd,
J = 13.7, 4.3 Hz, 1H, CH (18)), 2.40 (dd, J = 12.6, 6.6 Hz, 1H, CHa (1)), 2.03–1.89
(m, 2H, CHa (11)+CHb (11)), 1.82–1.65 (m, 2H, CHa (22)+CHa (15)), 1.66–1.40
(m, 9H, CH (9)+CHa (19)+CHa (7)+CHb (7)+CHb (22)+CHa (16)+CHb (16)+CHa
(6)+CHb (6)), 1.40–1.04 (m, 6H, CHb (1)+CH (5)+CHb (19)+CHa (21)+CHb
(21)+CHb (15)), 1.26 (s, 3H, CH3 (25)), 1.16 (s, 3H, CH3 (23)), 1.10 (s, 3H, CH3
31. Selected properties of 7: colorless solid; mp: 310–314 °C (lit.: 308–310 °C Ref.
26).
32. For HPLC: Prontosil C-18, MeOH/H2O 86:6, 1% H3PO4.