Total synthesis of (-)-2-epi-lentiginosine by use of chiral 5-hydroxy-1,5-dihydropyrrol-2-one as a building block

Article abstract of DOI:10.1016/j.tetlet.2007.10.125

We have developed a practical synthesis of the chiral lactam as a new chiral building block for alkaloid synthesis. Lipase-catalyzed kinetic resolution of hydroxylactam 8, followed by isolation-racemization of the chiral acetoxylactam 9 provided the optic

Full text of DOI:10.1016/j.tetlet.2007.10.125

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Tetrahedron Letters 48 (2007) 8956–8959
Total synthesis of (ꢀ)-2-epi-lentiginosine by use of chiral
5-hydroxy-1,5-dihydropyrrol-2-one as a building block
Takayuki Muramatsu, Sho Yamashita, Yumiko Nakamura, Masahisa Suzuki,
Nobuyuki Mase, Hidemi Yoda and Kunihiko Takabe*
Department of Molecular Science, Faculty of Engineering, Shizuoka University, 3-5-1 Johoku, Hamamatsu 432-8561, Japan
Received 19 September 2007; revised 22 October 2007; accepted 25 October 2007
Available online 30 October 2007
Abstract—We have developed a practical synthesis of the chiral lactam as a new chiral building block for alkaloid synthesis. Lipase-
catalyzed kinetic resolution of hydroxylactam 8, followed by isolation–racemization of the chiral acetoxylactam 9 provided the opti-
cally pure hydroxylactam 8 in 96.0% yield with >99% ee after five cycles of kinetic resolution–racemization process. Chemical trans-
formation of (S)-hydroxylactam 8 furnished chiral (ꢀ)-2-epi-lentiginosine (1) in 20% yield in 10 steps with no loss of enantiomeric
excess.
ꢀ 2007 Elsevier Ltd. All rights reserved.
Polyhydroxylated indolizidines including (ꢀ)-2-epi-len-
tiginosine (1) are potent inhibitors of glycosidases and
are of potential use in cancer chemotherapy.1 (ꢀ)-2-
epi-Lentiginosine is a metabolite of the fungus Rhizocto-
nia leguminicol and has been postulated to arise biosyn-
thetically from L-lysine via L-pipecolic acid.2,3 Although
a large number of synthetic methods of polyhydroxylat-
ed indolizidines have been developed, these asymmetric
syntheses are mainly based on chiral pool approaches.1
More efficient methods for the preparation of such bio-
active compounds are highly desired. Recently, biocata-
lysts have become an important tool for the production
of pharmaceuticals and fine chemicals due to their high
enantio-, regio-, and chemo-selectivity.4 In addition,
they often provide more environmentally friendly pro-
cesses than chemical catalysts. Suitable biocatalysts for
industrial and laboratory uses are commercially avail-
able now; however, they are still very limited. Therefore,
the search for a superior biocatalyst to synthesize new
chiral building blocks is an important field of study.
Recently, we reported that extremely high enantioselec-
tivity (E value = > 1000) was achieved in the lipase-cat-
alyzed kinetic resolution of racemic 5-hydroxy-1,5-
dihydropyrrol-2-one (rac)-5.5 Both enantiomers of 5
were easily attained in 49% yield with >99% ee. Herein,
we report how the new chiral building block 5 can be
utilized to prepare (ꢀ)-2-epi-lentiginosine (1) in high
enantiomeric excess. The retrosynthesis is depicted in
Scheme 1. Ring-closure metathesis of diallyl lactam 2
is a key reaction to form a bicyclic compound contain-
ing the three contiguous chiral centers. The chiral diol
3 is generated from the a,b-unsaturated lactam 4
employing a stereoselective dihydroxylation. The chiral
lactam 4 is obtained by lipase-catalyzed kinetic resolu-
tion of the racemic hydroxylactam 5 prepared from
maleic anhydride (6).
The p-methoxybenzyl (PMB) protecting group was cho-
sen as it can be removed selectively in later transforma-
tions. PMB-protected maleimide 7 was obtained in 90%
yield according to Toru’s procedure,6 following regiose-
lective 1,2-reduction7 using NaBH4/CeCl3 to afford the
Keywords: (ꢀ)-2-epi-Lentiginosine; Lipase-catalyzed kinetic resolution;
Chiral building block.
*
Scheme 1. Retrosynthesis of (ꢀ)-2-epi-lentiginosine (1) from maleic
anhydride (6).
Corresponding author. Tel./fax: +81 53 478 1148; e-mail:
tcktaka@ipc.shizuoka.ac.jp
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.10.125

T. Muramatsu et al. / Tetrahedron Letters 48 (2007) 8956–8959
8957
osmium tetraoxide/NMO catalyst in a mixed aqueous
solvent for 3 h afforded diol 12 in 91% yield with
(2S,3R,4S) configuration as a single diastereomer. Pro-
tection of the dihydroxy group with dimethoxypropane
furnished acetonide 13 in 82% yield accompanied by the
replacement of the acetoxy group to a methoxy group
(Scheme 4).
Acetonide 13 is a good substrate for the stereoselective
nucleophilic addition of trimethylsilyl compounds pro-
moted by boron trifluoride etherate via a well-known
N-acylpyrrolidinium ion intermediate (Scheme 5).9 Ster-
eoselective allylation of 13 with allyltrimethylsilane led
to the lactam 14 in 96% yield as a single diastereomer,
which is a good precursor of gastroprotective AI-77-B
agent as reported by Kotsuki et al.10 Treatment of 13
with the trimethylsilyl enol ether of pinacolone fur-
nished lactam 15 in 70% yield as a single diastereomer,
which has been transformed to the naturally occurring
(+)-calyculin A and (ꢀ)-calyculin B as reported by
Smith et al.9 Cyanation of 13 with trimethylsilyl cyanide
also gave lactam 16 as a mixture of diastereomers
((2S,3S,4S): (2R,3S,4S) = 4:1), but they were easily sep-
arated by silica gel chromatography to give the chiral
lactam 16 in 72% yield. The obtained cyanide 16 was
converted to chiral 3,4-dihydroxyglutamic acid 17 as
performed by Oba/Nishiyama et al.11
Scheme 2. Reagents and conditions: (a) PMBNH2, ZnCl2, HMDS,
toluene, reflux, 2 h; (b) CeCl3Æ7H2O, NaBH4, MeOH, 0 ꢁC, 2 h; (c)
AcOCH@CH2, lipase PS-D (Burkholderia cepacia, Amano Enzyme
Co, Ltd), 1,4-dioxane, rt, 24 h.
racemic hydroxylactam (rac)-8 in 84% yield in two steps.
Lipase PS-D catalyzed kinetic resolution of (rac)-8 fur-
nished acetate 9 with (R) stereochemistry in 49% yield
with >99% ee, along with the recovered alcohol 8 with
(S) stereochemistry in 49% yield with >99% ee (Scheme
2).8
We further investigated a racemization of the chiral
alcohol (S)-8 and the chiral acetate (R)-9 to improve
the total chemical yield (Scheme 3). Chiral acetate (R)-
9 was subjected to racemization in the presence of scan-
dium trifluoromethanesulfonate to give the racemic
alcohol 8 in quantitative yield at 50 ꢁC; similarly, the
chiral alcohol 8 was completely racemized at 25 ꢁC. This
racemization probably proceeded through the same
iminium cation intermediate 10.9 Alternatively, a more
practical racemization was attained under basic condi-
tions using sodium hydroxide. It is probable that the
achiral anion intermediate 11 is formed during the race-
mization process.
Table 1. Cycles of kinetic resolution and racemization
Theoretically, chiral (S)-8 and/or (R)-9 should be ob-
tained in 97% yield after five cycles of resolution–race-
mization processes. In fact, lipase-catalyzed kinetic
resolution of hydroxylactam (rac)-8, followed by isola-
tion–racemization of the chiral acetoxylactam (R)-9 pro-
vided the optically pure hydroxylactam (S)-8 in 96.0%
yield with >99% ee after five cycles of kinetic resolu-
tion–racemization process (Table 1). The similar syn-
thetic sequence including racemization of (S)-8 to
(rac)-8 may be used to prepare (R)-9 in high chemical to-
tal yield.
Cycles
Kinetic resolution
(rac)-8!(R)-9 + (S)-8
Racemization
(R)-9!(rac)-8
(R)-9 Yield (ee), % (S)-8 Yield (ee), % rac-8 Yield (%)
1st
50 (>99)
49 (>99)
49 (>99)
50 (>99)
50 (>99)
48 (>99)
50 (>99)
48 (>99)
50 (>99)
50 (>99)
99
99
98
95
99
2nd
3rd
4th
5th
Reagents and conditions: (a) AcOCH@CH2, lipase PS-D (Burkholderia
cepacia, Amano Enzyme Co., Ltd), 1,4-dioxane, rt, 24 h; (b) NaOH
(1 equiv), H2O (2 equiv), THF, 25 ꢁC, 24 h.
Stereoselective dihydroxylation of lactam (S)-9 was
performed by osmium oxidation. Exposure of (S)-9 to
Scheme 3. Reagents and conditions: (a) from (S)-8: Sc(OTf)3 (1 equiv), H2O (2 equiv), THF, 25 ꢁC, 7 h; from (R)-9: Sc(OTf)3 (1 equiv), H2O
(2 equiv), THF, 50 ꢁC, 22 h; (b) NaOH (1 equiv), H2O (2 equiv), THF, 25 ꢁC, 24 h.

8958
T. Muramatsu et al. / Tetrahedron Letters 48 (2007) 8956–8959
Scheme 4. Reagents and conditions: (a) Ac2O, Et3N, CH2Cl2, rt, 10 h;
(b) OsO4, NMO, H2O/acetone/MeCN = 1:1:1, rt, 3 h; (c)
Me2C(OMe)2, p-TsOH, acetone, rt, 24 h.
Scheme 6. Reagents and conditions: (a) CAN, H2O-MeCN, 0 ꢁC, 3 h;
(b) NaH, BrCH2CH@CH2, DMF, 0 ꢁC–rt, 4 h; (c) Grubbs cat.,
CH2Cl2, rt, 3 h; (d) PtO2, H2 (0.4 MPa), AcOEt, rt, 4 h; (e) BH3ÆTHF,
THF, 55 ꢁC, 12 h, then 1 N HCl, reflux, 30 min; (f) Dowex 1X8-50
(OHꢀ form).
(S)-8 and/or (R)-9 in high total chemical yield. Chemical
transformation of (S)-alcohol 8 provided chiral (ꢀ)-2-
epi-lentiginosine (ꢀ)-1 in 20% yield in 10 steps with no
loss of enantiomeric excess. Further studies focusing
on the use of the chiral lactam (S)-8 and/or (R)-9 as a
new chiral building block in total synthesis of natural
compounds are currently under investigation and will
be reported in due course.
Acknowledgements
We would like to thank Amano Enzyme Co., Ltd for a
generous gift of enzymes. This work was supported in
part by a Grant-in-Aid for Scientific Research from
Japan Society for the Promotion of Science. We grate-
fully acknowledge Dr. D. D. Steiner for a scientific
discussion.
Scheme 5. Reagents and conditions: (a) Me3SiCH2CH@CH2,
BF3ÆOEt2, CH2Cl2, ꢀ78 ꢁC–rt, 20 h; (b) Me3SiOC(t-Bu)@CH2,
BF3ÆOEt2, CH2Cl2, 0 ꢁC–rt, 20 h; (c) Me3SiCN, BF3ÆOEt2, CH2Cl2,
0 ꢁC–rt, 20 h.
Lactam 14 was subjected to deprotection of the PMB
group with cerium ammonium nitrate (CAN), and then
allylation of 18 with allyl bromide gave lactam 19 in 62%
yield. Ring-closing olefin metathesis of diallyl lactam 19
in the presence of Grubbs’ first-generation catalyst effec-
tively proceeded to give the bicyclic lactam 20 in 91%
yield. Platinum oxide catalyzed hydrogenation of 20
followed by borane reduction and desalting on Dowex
1 · 8–50 afforded (ꢀ)-2-epi-lentiginosine (1). The physi-
cal properties of synthetic (ꢀ)-2-epi-lentiginosine (ꢀ)-1
were in complete agreement with those reported in the
References and notes
1. Stutz, A. E. Iminosugars as Glycosidase Inhibitors, Nojir-
imycin and Beyond; Wiley-VCY: Weinheim, 1999.
2. (a) Colegate, S. M.; Dorling, P. R.; Huxtable, C. R. Aust.
J. Chem. 1984, 37, 1503–1509; (b) Harris, T. M.; Harris, C.
M.; Hill, J. E.; Ungemach, F. S.; Broquist, H. P.;
Wickwire, B. M. J. Org. Chem. 1987, 52, 3094–3098; (c)
Harris, C. M.; Campbell, B. C.; Molyneux, R. J.; Harris,
T. M. Tetrahedron Lett. 1988, 29, 4815–4818; (d) Harris,
C. M.; Schneider, M. J.; Ungemach, F. S.; Hill, J. E.;
Harris, T. M. J. Am. Chem. Soc. 1988, 110, 940–949; (e)
Pastuszak, I.; Molyneux, R. J.; James, L. F.; Elbein, A. D.
Biochemistry 1990, 29, 1886–1891.
24
25
literature2,3,12 ð½aꢁD ꢀ31.3 (c 0.54, CHCl3), lit.2e ½aꢁD
ꢀ32.5 (c 0.44, CHCl3). The same synthetic sequence
may be used to prepare ent-1 starting from readily avail-
able (R)-9 (Scheme 6).
3. Asymmetric syntheses: (a) Heitz, M. P.; Overman, L. E.
J. Org. Chem. 1989, 54, 2591–2596; (b) Lim, S. H.; Ma, S.;
Beak, P. J. Org. Chem. 2001, 66, 9056–9062; (c) Rasmus-
sen, M. O.; Delair, P.; Greene, A. E. J. Org. Chem. 2001,
66, 5438–5443; (d) Sawada, D.; Takahashi, H.; Ikegami, S.
Tetrahedron Lett. 2003, 44, 3085–3088.
4. (a) Breslow, R. Artificial Enzymes; Wiley-VCH: Wein-
heim, 2005; (b) Buchholz, K.; Kasche, V.; Bornscheuer, U.
T. Biocatalysts and Enzyme Technology; Wiley-VCH:
Weinheim, 2005; (c) Drauz, K.; Waldmann, H. Enzyme
In summary, we have developed a practical synthesis of
the chiral lactams (S)-8 and/or (R)-9 as new chiral build-
ing blocks for a multitude of important optically pure
products. Lipase-catalyzed kinetic resolution of lactam
8 demonstrates excellent enantioselectivity. Further-
more, these lactams are easily racemized under acidic
and/or basic conditions. Therefore, the kinetic resolu-
tion–racemization processes provided chiral lactam

T. Muramatsu et al. / Tetrahedron Letters 48 (2007) 8956–8959
8959
Catalysis in Organic Synthesis; Wiley-VCH: Weinheim,
2002.
5. Takabe, K.; Suzuki, M.; Nishi, T.; Hiyoshi, M.; Taka-
mori, Y.; Yoda, H.; Mase, N. Tetrahedron Lett. 2000, 41,
9859–9863.
129.16 (CH), 127.15 (C), 113.57 (CH), 85.16 (CH), 69.86
(CH), 69.15 (CH), 54.65 (OCH3), 44.38 (CH2), 20.04
(CH3); MS (EI) m/z 295 (M+, 1), 235 (15),178 (28), 136
(34), 121 (100); Anal. Calcd: C, 56.94; H, 5.80; N, 4.74.
25
Found: C, 56.75; H, 5.72; N, 4.61. Compound 13: ½aꢁD
6. Reddy, P. Y.; Kondo, S.; Toru, T.; Ueno, Y. J. Org.
Chem. 1997, 62, 2652–2654.
+58.9 (c 0.79, CHCl3); 1H NMR (300 MHz, CDCl3)
d = 1.33 (s, 3H, –CH3), 1.34 (s, 3H, –CH3), 3.30 (s, 3H,
–OCH3), 3.78 (s, 3H, ArOCH3), 3.94 (d, J = 14.5 Hz, 1H,
–CH2), 4.43 (d, J = 6.0 Hz, 1H, –CHa), 4.47 (d,
J = 0.7 Hz, 1H, –CHOCH3), 4.78 (dd, J = 0.7, 6.0 Hz,
1H, –CHb), 4.92 (d, J = 14.5 Hz, 1H, –CH2), 6.85 (d,
J = 8.7 Hz, 2H, H-2, H-6), 7.18 (d, J = 8.7 Hz, 2H, H-3,
H-5); 13C NMR (75 MHz, CDCl3) d = 171.05 (C@O),
159.39 (C), 129.90 (CH), 127.15 (C), 114.15 (CH), 113.22
(C), 91.04 (CH), 76.97 (CH), 76.33 (CH), 55.20 (OCH3),
54.75 (OCH3), 43.43 (CH2), 26.92 (CH3), 25.70 (CH3); MS
(EI) m/z 307 (M+, 17), 87 (100); Anal. Calcd: C, 62.53; H,
6.89; N, 4.56. Found: C, 62.38; H, 6.81; N, 4.38.
Compound 14: registry number (3aS, 6S, 6aS)-154850-78-
7. Mase, N.; Nishi, T.; Hiyoshi, M.; Ichihara, K.; Bessho, J.;
Yoda, H.; Takabe, K. J. Chem. Soc. Perkin Trans. 1 2002,
707–709.
8. Novozym 435 (Novozymesꢂ, Candida antarctica) and
lipase PSA-30 (Amano, Pseudomonas cepacia) were also a
practical catalyst for this kinetic resolution (>49% yield,
22
>99% ee). Compound (S)-8: ½aꢁD ꢀ29.0 (c 1.1, MeOH); 1H
NMR (300 MHz, CDCl3) d = 2.11 (d, J = 11.2 Hz, 1H,
–OH), 3.79 (s, 3H, –OCH3), 4.22 (d, J = 14.8 Hz, 1H,
–CH2), 4.87 (d, J = 14.8 Hz, 1H, –CH2), 5.26 (d,
J = 11.2 Hz, 1H, –CHOH), 6.20 (d, J = 5.9 Hz, 1H,
–CHa), 6.85 (d, J = 8.7 Hz, 2H, H-2, H-6), 6.91 (dd,
J = 1.6, 5.9 Hz, 1H, –CHb), 7.24 (d, J = 8.7 Hz, 2H, H-3,
H-5); 13C NMR (75 MHz, CDCl3) d = 169.38 (C@O),
159.15 (C), 145.80 (CH), 129.71 (CH), 129.32 (CH), 128.51
(CH), 114.12 (CH), 82.56 (CH), 55.20 (OCH3), 42.01
(CH2); MS (EI) m/z 219 (M+, 9), 136 (100), 121 (26); Anal.
Calcd: C, 65.74; H, 5.98; N, 6.39. Found: C, 65.83; H,
5.91; N, 6.24. HPLC (Daicel CHIRALPAK AS-H,
hexane/2-PrOH = 80:20, flow rate 0.5 mL/min, k =
254 nm) tR = 32.7 (R-isomer), 35.9 (S-isomer) min. Com-
28
22
9; ½aꢁD +39.2 (c 0.75, CHCl3), (lit.9 ½aꢁD +37.0 (c 2.0,
CHCl3)); 1H NMR (200 MHz, CDCl3) d = 1.34 (s, 3H,
–CH3), 1.39 (s, 3H, –CH3), 2.1–2.5 (m, 2H), 3.53 (dd,
J = 7.0, 3.6 Hz, 1H), 3.79 (s, 3H, –OCH3), 3.89 (d,
J = 14.8 Hz, 1H), 4.39 (d, J = 5.7 Hz, 1H), 4.67 (dd,
J = 5.7, 0.6 Hz, 1H), 4.99 (d, J = 14.8 Hz, 1H), 5.06–5.22
(m, 2H), 5.48–5.72 (m, 1H), 6.85 (d, J = 8.6 Hz, 2H), 7.17
(d, J = 8.6 Hz, 2H). Compound 18: registry number (3aS,
6S, 6aS)-154850-79-0; 1H NMR (200 MHz, CDCl3)
d = 1.37 (s, 3H, –CH3), 1.47 (s, 3H, –CH3), 2.1–2.5 (m,
2H), 3.73 (t, J = 6.3 Hz, 1H), 4.45 (d, J = 5.9 Hz, 1H),
4.45 (d, J = 5.9 Hz, 1H), 5.02–5.30 (m, 2H), 5.6–5.9 (m,
1H), 6.98 (bs, 1H, N–H). Compound 19: 1H NMR
(90 MHz, CDCl3) d = 2.05–2.65 (m, 2H), 1.37 (s, 3H,
–CH3), 1.43 (s, 3H, –CH3), 3.30–3.90 (m, 2H), 4.20–4.35
(m, 1H), 4.43 (d, J = 5.6 Hz, 1H), 4.64 (d, J = 5.6 Hz, 1H),
5.05–6.10 (m, 6H); MS (EI) m/z 237 (M+, 0.5), 196 (19), 85
22
pound (R)-9: ½aꢁD ꢀ30.2 (c 1.1, CHCl3); 1H NMR
(300 MHz, CDCl3) d = 1.97 (s, 3H, –COCH3), 3.79 (s,
3H, –OCH3), 4.28 (d, J = 15.0 Hz, 1H, –CH2), 4.71 (d,
J = 15.0 Hz, 1H, –CH2), 6.28 (d, J = 6.0 Hz, 1H, –CHa),
6.43 (d, J = 1.5 Hz, 1H, –CHOAc), 6.84 (d, J = 8.7 Hz,
2H, H-2, H-6), 6.92 (dd, J = 1.5, 6.0 Hz, 1H, –CHb), 7.18
(d, J = 8.7 Hz, 2H, H-3, H-5); 13C NMR (75 MHz,
CDCl3) d = 170.22 (C@O), 169.77 (C@O), 159.03 (C),
142.36 (CH), 129.63 (CH), 129.34 (CH), 128.76 (C), 113.87
(CH), 82.13 (CH), 55.02 (OCH3), 43.13 (CH2), 20.36
(CH3); MS (EI) m/z 261 (M+, 3), 201 (55), 136 (100), 121
(94); Anal. Calcd: C, 64.36; H, 5.79; N, 5.36. Found: C,
64.11; H, 5.56; N, 5.56. HPLC (Daicel CHIRALPAK AS-
H, hexane/2-PrOH = 80:20, flow rate 0.5 mL/min,
k = 254 nm)tR = 55.0 (R-isomer), 59.8 (S-isomer) min.
9. Smith, A. B., III; Friestad, G. K.; Barbosa, J.; Bertoun-
esque, E.; Duan, J. J. W.; Hull, K. G.; Iwashima, M.; Qiu,
Y.; Spoors, P. G.; Salvatore, B. A. J. Am. Chem. Soc.
1999, 121, 10478–10486.
1
(53), 41 (100). Compound 20: H NMR (90 MHz, CDCl3)
d = 1.55–2.65 (m, 2H), 1.39 (s, 3H, –CH3), 1.46 (s, 3H,
–CH3), 3.40–3.85 (m, 2H), 4.20–4.35 (m, 1H), 4.42 (d,
J = 6.5 Hz, 1H), 4.67 (d, J = 6.5 Hz, 1H), 5.50–5.95 (m,
2H); MS (EI) m/z 209 (M+, 4), 194 (21), 134 (22), 100 (16),
85 (32), 81 (26), 54 (74), 43 (100). Compound 21: registry
24
number (3aS, 9aS, 9bS)-359866-28-7; ½aꢁD +31.3 (c 0.89,
25
CHCl3) (lit.3c ½aꢁD +31.3 (c 1.00, CHCl3)); 1H NMR
(90 MHz, CDCl3) d = 1.00–1.70 (m, 4H), 1.35 (s, 3H,
–CH3), 1.42 (s, 3H, –CH3), 1.71–2.15 (m, 2H), 2.50–2.95
(m, 1H), 3.47 (dd, J = 2.6, 12.3 Hz, 1H), 4.05–4.40 (m, 1
H), 4.32 (d, J = 6.0 Hz, 1H), 4.62 (d, J = 6.0 Hz, 1H); MS
(EI) m/z 211 (M+, 2), 196 (30), 136 (31), 100 (30), 83 (80),
10. Kotsuki, H.; Araki, T.; Miyazaki, A.; Iwasaki, M.; Datta,
P. K. Org. Lett. 1999, 1, 499–502.
11. Oba, M.; Koguchi, S.; Nishiyama, K. Tetrahedron 2004,
60, 8089–8092.
55 (55), 43 (100). Compound (ꢀ)-1: registry number
24
(1S,2R,8aS)-108866-42-8((ꢀ)-2-epi-lentiginosine);
½aꢁD
26
25
12. Compound 12: ½aꢁD +80.1 (c 0.51, MeOH); 1H NMR
ꢀ31.3 (c 0.54, CHCl3) (lit.2e ½aꢁD ¼ ꢀ32:5ꢂ (c 0.44,
CHCl3)); 1H NMR (90 MHz, CDCl3) d = 1.05–1.40 (m,
2H), 1.41–1.75 (m, 2H), 1.76–2.40 (m, 7H), 2.80–3.22 (m,
1H), 3.23–3.85 (m, 2H), 4.05–4.50 (m, 1H); 13C NMR
(22.5 MHz, CDCl3) d = 74.8 (CH), 67.9 (CH), 67.1 (CH),
61.8 (CH2), 52.8 (CH2), 28.5 (CH2), 24.9 (CH2), 23.7
(CH2); MS (EI) m/z 157 (M+, 14), 140 (8), 97 (100), 84
(24), 69 (39).
(300 MHz, CDCl3) d = 1.98 (s, 3H, –OAc), 3.00–5.00 (br
s, 2H, 2 · –OH), 3.79 (s, 3H, –OCH3), 4.22 (d, J = 4.8 Hz,
1H, –CHa), 4.26 (d, J = 14.8 Hz, 1H, –CH2), 4.56 (d,
J = 4.8 Hz, 1H, –CHb), 4.65 (d, J = 14.8 Hz, 1H, –CH2),
5.94 (s, 1H, –CHOAc), 6.84 (d, J = 8.7 Hz, 2H, H-2, H-6),
7.18 (d, J = 8.7 Hz, 2H, H-3, H-5); 13C NMR (75 MHz,
CDCl3) d = 174.62 (C@O), 169.76 (C@O), 158.81 (C),