Enantioselective synthesis of (-)-lasubine II

Article abstract of DOI:10.1016/j.tetlet.2009.07.128

A highly enantioselective synthesis of lythraceae alkaloid lasubine II has been achieved using organo-catalyzed Mannich reaction, Maruoka allylation, and aza-Michael addition as the key steps.

Full text of DOI:10.1016/j.tetlet.2009.07.128

Tetrahedron Letters 50 (2009) 5686–5688
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Enantioselective synthesis of (ꢀ)-lasubine II
*
S. Chandrasekhar , R. V. N. S. Murali, Ch. Raji Reddy
Organic Division-I, Indian Institute of Chemical Technology, Hyderabad 500 607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly enantioselective synthesis of lythraceae alkaloid lasubine II has been achieved using organo-cat-
alyzed Mannich reaction, Maruoka allylation, and aza-Michael addition as the key steps.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 9 June 2009
Revised 17 July 2009
Accepted 24 July 2009
Available online 28 July 2009
Keywords:
Alkaloid
Lasubine
Organocatalysis
Mannich reaction
Aza-Michael addition
Maruoka allylation
(ꢀ)-Lasubine I (1) and (ꢀ)-lasubine II (2, Figure 1) were isolated
from the leaves of Lagerstroemia subcostata koehne by Fuji et al. in
1978.1 These Lythraceae alkaloids containing the arylquinolizidine
ring systems have been found to have a broad range of biological
activities.2 The quinolizidine scaffold of these molecules has
attracted great interest from synthetic chemistry point of view
and various syntheses have been reported in either racemic form
or enantiomerically pure form.3–6 Herein, we report a new strategy
for lasubine II that incorporates organocatalysis and Michael reac-
tion which are our continued interests for synthesis of bio-active
natural products.7,8
Accordingly our synthesis commenced with the commercially
available starting material, 3,4-dimethoxy benzaldehyde 3 and
the key steps in the sequence include organo-catalyzed Mannich
reaction, Maruoka allylation, and aza-Michael addition reactions,
which would be generating the asymmetric centers to provide
the (ꢀ)-lasubine II (Schemes 1 and 2). In the first step, 3,4-dime-
thoxy benzaldehyde 3 was treated with BocNH2 to generate Boc-
imine 4.9 The compound 4 was subjected to proline-catalyzed
Mannich reaction10 with acetaldehyde to obtain the b-amino alde-
hyde 5, which was immediately subjected to Maruoka allylation11
using titanium complex (S,S)-I and allyltributylstannane to furnish
the 1,3-amino alcohol 6 in 72% yield with 97% enantiomeric excess
(Scheme 1).12 The enantiomeric excess of Mannich product 5 was
confirmed by chiral HPLC method (>98% ee) in its alcohol form.13
The relative stereochemistry of compound 6 was thoroughly exam-
ined at a later stage using intermediate 9. Thus, 6 was subjected to
dihydroxylation (OsO4/NMO) followed by sodium periodate oxida-
tion and Wittig olefination with ethoxycarbonylmethylene tri-
phenylphosphorane to afford
a,b-unsaturated ester 7. Now, the
compound 7 was ready for intramolecular aza-Michael addition
reaction,14 which was successfully achieved by the treatment of
7 with 1% HCl in isopropanol at 60 °C for 4 h to afford 2,4,6-trisub-
stituted piperidine 8 in 73% yield. It was gratifying to find that the
exclusive product of the reaction was the 2,6-cis-isomer, which
was confirmed by NOE studies performed on compound 9.15 The
hydroxyl group of the piperidine that was obtained above was pro-
tected as tert-butyldimethylsilyl ether using TBSOTf/DIPEA in
dichloromethane to get compound 9. Exposure of compound 9 to
DIBAL-H reduction followed by the addition of ethoxycarbonyl-
methylene triphenylphosphorane provided
a,b-unsaturated ester
10 in 54% yield over two steps. Conversion of
a,b-unsaturated ester
10 to saturated ester 11 was achieved by NiCl2, NaBH4 reduction
and further reduction of ester using DIBAL-H provided the satu-
rated alcohol 12. Deprotection of TBS group of 12 by TBAF in THF
OH
N
OH
N
H
H
MeO
MeO
OMe
(-)-Lasubine I
Figure 1. Structure of (ꢀ)-lasubine I (1) and (ꢀ)-lasubine II (2).
OMe
2
1
(-)-Lasubine II
* Corresponding author. Tel.: +91 040 27193210; fax: +91 040 27160512.
E-mail address: srivaric@iict.res.in (S. Chandrasekhar).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.07.128

S. Chandrasekhar et al. / Tetrahedron Letters 50 (2009) 5686–5688
5687
Boc
Boc
NBoc
H
NH
O
NH OH
CHO
OiPr
O
O
c
Ti
a
b
H
O
Ti
O
MeO
MeO
iPrO
O
MeO
MeO
OMe
OMe
3
4
6
OMe
OMe
5
(S, S)-I
Scheme 1. Reagents and conditions: (a) (i) BocNH2, PhSO2Na, HCOOH, MeOH:H2O (1:9), rt, 9 h; (ii) K2CO3, Na2SO4, THF, reflux, 24 h 73% over two steps; (b) CH3CHO,
(20 mol %), CH3CN, 0 °C, 3 h, 64%; (c) (S, S)-I (10 mol %), Bu3SnCH2CH@CH2, CH2Cl2, ꢀ15 °C to 0 °C, 24 h, 72%.
L-proline
OH
OTBS
Boc
NH OH
COOEt
d
a
b
c
COOEt
COOEt
6
N
H
N
H
MeO
7
MeO
8
MeO
9
OMe
OMe
OMe
OTBS
OH
OTBS
OTBS
h
g
e
f
N
H
N
2
N
N
H
H
H
MeO
MeO
MeO
MeO
(-)-Lasubine- (II)
OMe
OMe
OMe
COOEt
OMe
COOEt
HO
HO
10
11
12
13
Scheme 2. Reagents and conditions: (a) (i) OsO4, NMO, acetone:H2O (8:2), rt, 14 h; (ii) NaIO4, CH2Cl2:H2O (8:2), rt, 0.5 h; (iii) Ph3P@CHCOOEt, benzene, rt, 4 h, 62% over three
steps; (b) 1% HCl in iPrOH, 60 °C, 4 h, 73%; (c) TBSOTf , DIPEA, CH2Cl2, 0 °C, 1 h, 76%; (d) (i) DIBAL-H, toluene, ꢀ78 °C, 2 h, (ii) Ph3P@CHCOOEt, benzene, rt, 4 h, 54% over two
steps; (e) NiCl2, NaBH4, CH3OH, 0 °C, 1 h, 67 %; (f) DIBAL-H, CH2Cl2, 0 °C, 3 h, 62 %; (g) 1 M TBAF solution in THF, rt, 6 h, 76%; (h) TsCl, pyridine, ꢀ20 °C to 0 °C, 8 h, 68%.
Ratni, H.; Kuendig, E. P. Org. Lett. 1999, 1, 1997; (d) Davis, F. A.; Rao, A.; Carroll,
P. J. Org. Lett. 2003, 5, 3855; (e) Liu, S.; Fan, Y.; Peng, X.; Wang, W.; Hua, W.;
Akber, H.; Liao, L. Tetrahedron Lett. 2006, 47, 7681.
gave diol 13, which upon treatment with TsCl–pyridine conditions
gave the target molecule (ꢀ)-lasubine II (2) in 68% yield (Scheme
2),16 having spectroscopic data (½a 2D6
ꢀ41.5, c 0.15, MeOH) identical
ꢁ
6. For enantioselective syntheses of (ꢀ)-lasubine II, see: (a) Ukaji, Y.; Ima, M.;
Yamada, T.; Inomata, K. Heterocycles 2000, 52, 563; (b) Davis, F. A.; Chao, B. Org.
Lett. 2000, 2, 2623; (c) Ma, D.; Zhu, W. Org. Lett. 2001, 3, 3927; (d) Back, T. G.;
with previously reported data.1,6
In conclusion, we have demonstrated an enantioselective total
synthesis of lythraceae alkaloid, (ꢀ)-lasubine II (2). Employing
organo-catalyzed Mannich reaction, Maruoka allylation, and aza-
Michael addition reaction, the asymmetric centers were generated.
This strategy is currently pursued for the synthesis of other aryl-
quinolizidine class of natural products.
´
Hamilton, M. D. Org. Lett. 2002, 4, 1779; (e) Gracias, V.; Zeng, Y.; Desai, P.; Aube,
J. Org. Lett. 2003, 5, 4999; (f) Zaja, M.; Blechert, S. Tetrahedron 2004, 60, 9629;
(g) Back, T. G.; Hamilton, M. D.; Lim, V. J. J.; Parvez, M. J. Org. Chem. 2005, 70,
967; (h) Lim, J.; Kim, G. Tetrahedron Lett. 2008, 49, 88; (i) Verkade, J. M. M.; Pijl,
F.; Willems, M. M. J. H. P.; Quaedflieg, P. J. L. M.; Delft, F. L.; Rutjes, F. P. J. T. J.
Org. Chem. 2009, 74, 3207.
7. (a) Chandrasekhar, S.; Narsihmulu, Ch.; Reddy, N. R.; Sultana, S. S. Tetrahedron
Lett. 2004, 45, 4581; (b) Chandrasekhar, S.; Narsihmulu, Ch.; Reddy, N. R.;
Sultana, S. S. Chem. Commun. 2004, 2450; (c) Chandrasekhar, S.; Reddy, N. R.;
Sultana, S. S.; Narsihmulu, Ch.; Reddy, K. V. Tetrahedron 2006, 62, 338; (d)
Chandrasekhar, S.; Tiwari, B.; Parida, B. B.; Reddy, Ch. R. Tetrahedron:
Asymmetry 2008, 19, 495.
8. (a) Chandrasekhar, S.; Prakash, S. J.; Shyamsunder, T. Tetrahedron Lett. 2005, 46,
6651; (b) Chadrasekhar, S.; Rambabu, Ch.; Prakash, S. J. Tetrahedron Lett. 2006,
47, 1213; (c) Chandrasekhar, S.; Reddy, N. R.; Rao, Y. S. Tetrahedron 2006, 62,
12098; (d) Chandrasekhar, S.; Rambabu, Ch.; Shyamsunder, T. Tetrahedron Lett.
2007, 48, 4683; (e) Chandrasekhar, S.; Rambabu, Ch.; Reddy, A. S. Tetrahadron
Lett. 2008, 49, 4476.
Acknowledgments
We thank UGC, New Delhi, for the research fellowship to
R.V.N.S.M. and DST, New Delhi for research grant (GAP-0154).
We also thank the reviewers for suggestions.
References and notes
9. Wenzel, A. G.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 12964.
10. (a) Yang, J. W.; Chandler, C.; Stadler, M.; Kampen, D.; List, B. Nature 2008, 452,
453; (b) Hayashi, Y.; Okano, T.; Itoh, T.; Urushima, T.; Ishikawa, H.; Uchimaru,
T. Angew. Chem. Int. Ed. 2008, 47, 9053.
11. Hanawa, H.; Hashimoto, T.; Maruoka, K. J. Am. Chem. Soc. 2003, 125, 1708.
12. Enantiomeric excess of compound 6 was determined by HPLC chiral pak IC
(250 ꢂ 4.6 mm), flow 1.0 mL/min (15% isopropanol in n-hexane), retention
time 11.79 (1.17%), 13.57 (98.83%).
1. Fuji, K.; Yamada, T.; Fujita, E.; Murata, H. Chem. Pharm. Bull. 1978, 26, 2515.
2. For reviews, see: (a) Golebiewski, W. M.; Wróbel, J. T.. In The Alkaloids:
Chemistry and Physiology; Rodrigo, R. G. A., Ed.; Academic: New York, 1981; Vol.
18, p 263; (b) Fuji, K.. In The Alkaloids; Academic Press: New York, 1989; Vol. 35.
Chapter 3, p 155; (c) Michael, J. P. Nat. Prod. Rep. 1993, 51; (d) Michael, J. P. Nat.
Prod. Rep. 1997, 14, 21; (e) Mitchinson, A.; Nadin, A. J. Chem. Soc., Perkin Trans. 1
2000, 2862; (f) Michael, J. P. Nat. Prod. Rep. 2008, 25, 139.
3. For the racemic syntheses of lasubine I, see: (a) Iida, H.; Tanaka, M.; Kibayashi,
C. J. Chem. Soc., Chem.Commun. 1983, 1143; (b) Iida, H.; Tanaka, M.; Kibayashi,
C. J. Org. Chem. 1984, 49, 1909; (c) Ent, H.; De Koning, H.; Speckamp, W. N.
Heterocycles 1988, 27, 237; (d) Beckwith, A. L. J.; Joseph, S. P.; Mayadunne, R. T.
A. J. Org. Chem. 1993, 58, 4198; (e) Bardot, V.; Gardette, D.; Gelas-Mialhe, Y.;
Gramain, J.-C.; Remuson, R. Heterocycles 1998, 48, 507.
13. Compound 5 was reduced to its alcohol using NaBH4 in MeOH at 0 °C as shown
below. Enantiomeric excess of this stable alcohol was determined by HPLC
chiral pak IC (250 ꢂ 4.6 mm), flow rate 1.2 mL/min (12% isopropanol in n-
hexane), retention time 34.36 (99.06%), 39.61 (0.93%).16
Boc
Boc
NH
O
NH
4. For the racemic syntheses of lasubine II, see: (a) Narasaka, K.; Yamazaki, S.; Ukaji,
Y. Chem. Lett. 1985, 1177; (b) Hoffmann, R. W.; Endesfelder, A. Liebigs Ann. Chem.
1986, 1823; (c) Narasaka, K.; Ukaji, Y.; Yamazaki, S. Bull. Chem. Soc. Jpn. 1986, 59,
525; (d) Brown, J. D.; Foley, M. A.; Comins, D. L. J. Am. Chem. Soc. 1988, 110, 7445;
(e)Pilli, R. A.;Dias, L. C.; Maldaner, A. O. TetrahedronLett. 1993, 34, 2729;(f)Pilli, R.
A.; Dias, L. C.; Maldaner, A. O. J. Org. Chem. 1995, 60, 717.
H
OH
NaBH4, MeOH
oC, 30 min.,
98%
MeO
MeO
5
5a
0
OMe
OMe
5. For enantioselective syntheses of (ꢀ)-lasubine I, see: (a) Comins, D. L.;
LaMunyon, D. H. J. Org. Chem. 1992, 57, 5807; (b) Chalard, P.; Remuson, R.;
Gelas-Mialhe, Y.; Gramain, J.-C. Tetrahedron: Asymmetry 1998, 9, 4361; (c)
14. Felpin, F. X.; Lebreton, J. J. Org. Chem. 2002, 67, 9192.
15. NOE experiment has been carried out on TBS-protected compound (9) and key
NOE enhancements are shown below.

5688
S. Chandrasekhar et al. / Tetrahedron Letters 50 (2009) 5686–5688
Ethyl-2-((4S,6S)-4-(tert-butyldimethylsilyloxy)-6-(3,4-dimethoxyphenyl)piperidin-2-yl)
acetate (9): ½a 2D6
ꢁ
ꢀ34.5 (c 0.3, CHCl3); IR (KBr):
mmax 3448, 2927, 2858, 1729, 1636,
nOe enhancement
1221, 1101, 765 cmꢀ1
;
1H NMR (CDCl3, 300 MHz): d 6.93 (s, 1H), 6.88 (d, J = 8.2 Hz,
H
OTBS
H
1H), 6.80 (d, J = 8.2 Hz, 1H), 4.11 (q, J = 7.1 Hz, 2H), 3.88 (s, 3H), 3.85 (s, 3H), 3.82–
3.72 (m, 1H), 3.63 (d, J = 11.3 Hz, 1H), 3.18–3.08 (m, 1H), 2.45 (d, J = 5.9 Hz, 2H),
1.98–1.90 (m, 2H), 1.87–1.80 (m, 1H), 1.57–1.45 (m, 1H), 1.23 (t, J = 7.1 Hz, 3H),
0.87 (s, 9H), 0.06 (s, 3H), 0.05 (s, 3H); 13C NMR (CDCl3, 75 MHz): d 172.3, 148.9,
148.1, 136.9, 118.9, 110.9, 110.0, 69.9, 60.4, 59.3, 55.9, 51.6, 43.8, 41.6, 41.1, 25.8,
18.1, 14.2, ꢀ4.6; ESIMS: m/z 438 (M+H)+; HRMS: calcd for C23H40NO5Si (M+H)+:
438.2675, found: 438.2662.
HN
COOEt
MeO
OMe
16. Spectral data of selected new compounds: (S)-tert-butyl 1-(3,4-dimeth-
oxyphenyl)-3-hydroxypropylcarbamate (5a):
ꢀ27.9 (c 0.42, CHCl3); IR
(E)-Ethyl-4-((4S,6S)-4-(tert-butyldimethylsilyloxy)-6-(3,4-dimethoxyphenyl)piperidin-
½ ꢁ
a 2D7
2-yl)but-2-enoate (10): ½a D26
ꢁ
ꢀ37.9 (c 0.5, CHCl3); IR (KBr):
mmax 3423, 2928, 2854,
(KBr): mmax 3458, 2933, 1644, 1493, 1453, 1366, 1261, 1156, 1028, 768 cmꢀ1
;
1722, 1514, 1461, 1261, 1099, 840, 774 cmꢀ1
;
1H NMR (CDCl3, 300 MHz): d 6.99–
1H NMR (CDCl3, 300 MHz): d 6.81 (s, 1H), 6.79 (s, 1H), 6.76 (s, 1H), 5.76–5.48 (m,
1H), 4.04 (d, J = 5.5 Hz, 1H), 3.85 (s, 3H), 3.83 (s, 3H), 3.70–3.58 (m, 2H), 2.47 (t,
J = 5.8 Hz, 1H), 2.12–1.93 (m, 1H), 1.41 (s, 9H); 13C NMR (CDCl3, 75 MHz): d 156.3,
148.9, 148.0, 132.5, 118.2, 111.1, 109.7, 79.9, 63.1, 58.9, 55.8, 51.3, 39.5, 28.3;
ESIMS: m/z 334 (M+Na)+; HRMS calcd for C16H25NNaO5 (M+Na)+: 334.1625,
found: 334.1640.
6.77 (m, 4H), 5.89 (d, J = 15.7 Hz, 1H), 4.18 (q, J = 7.2 Hz, 2H), 3.90 (s, 3H), 3.87 (s,
3H), 3.82–3.70 (m, 1H), 3.68–3.53 (m, 1H), 2.90–2.77 (m, 1H), 2.51–2.26 (m, 2H),
1.99–1.80 (m, 1H), 1.77–1.67 (s, 2H), 1.59–1.43 (m, 1H), 1.28 (t, J = 7.0 Hz, 3H), 0.88
(s, 9H), 0.07 (s, 3H), 0.06 (s, 3H); 13C NMR (CDCl3, 75 MHz): d 162.9, 155.6, 149.9,
148.9, 145.5, 136.8, 123.8, 118.9, 110.9, 110.1, 70.1, 60.3, 59.5, 55.9, 54.0, 51.6, 44.1,
41.8, 39.5, 29.7, 25.8, 14.2, 13.9, ꢀ4.5; ESIMS: m/z 464 (M+H)+.
Tert-butyl (1S,3S)-1-(3,4-dimethoxyphenyl)-3-hydroxy hex-5-enylcarbamate (6):
4-((4S,6S)-4-(tert-butyldimethylsilyloxy)-6-(3,4-dimethoxyphenyl)piperidin-2-
a 2D5
ꢁ
ꢀ23.3 (c 0.4, CHCl3); IR (KBr): mmax 3366, 2926, 2853, 1693, 1513, 1259,
yl)butan-1-ol (12): ½a D26
ꢁ
ꢀ38.5 (c 0.2, CHCl3); IR (KBr): mmax 3384, 2925, 2855,
½
1166, 1028, 759 cmꢀ1 1H NMR (CDCl3, 300 MHz): d 6.80 (s, 2H), 6.78 (d,
;
1642, 1366, 1263, 1105, 840 cmꢀ1
;
1H NMR (CDCl3, 300 MHz); d 7.18 (d, J = 3.6 Hz,
J = 0.9 Hz, 1H), 5.91–5.73 (m, 1H), 5.13–5.01 (m, 3H), 4.84 (t, J = 7.4 Hz, 1H), 3.88
(s, 3H), 3.86 (s, 3H), 3.74–3.63 (m, 1H), 3.55 (br s, 1H), 2.31–2.18 (m, 2H), 1.83–
1.75 (m, 2H), 1.45 (s, 9H); 13C NMR (CDCl3, 75 MHz): d 156.3, 149.4, 148.6, 138.8,
135.1, 118.2, 117.5, 111.6, 111.4, 79.8, 67.3, 55.9, 51.7, 44.4, 41.8, 28.5; ESIMS: m/
z 374 (M+Na)+; HRMS: calcd for C19H29NNaO5 (M+Na)+: 374.1938, found:
374.1934.
1H), 6.99 (s, 1H), 6.91 (dd, J = 8.1, 1.9 Hz, 1H), 6.81 (d, J = 8.3 Hz, 1H), 3.91 (s, 3H),
3.87 (s, 3H), 3.82–3.70 (m, 1H), 3.61 (t, J = 6.0 Hz, 3H), 2.77–2.66 (m, 1H), 2.00–1.84
(m, 2H), 1.65–1.36 (m, 7H), 1.33–1.19 (m, 1H), 0.88 (s, 9H), 0.07 (s, 3H), 0.06 (s,
3H); 13C NMR (CDCl3, 75 MHz): d 148.9, 148.2, 136.2, 119.1, 111.0, 110.2, 70.1,
62.6, 59.6, 55.9, 55.4, 43.7, 41.7, 36.2, 32.5, 25.8, 22.1, 18.1, ꢀ4.6; ESIMS: m/z 424
(M+H)+; HRMS: calcd for C23H42NO4Si (M+H)+: 424.2878, found: 424.2878.
(2S,4S)-2-(3,4-dimethoxyphenyl)-6-(4-hydroxybutyl) piperidin-4-ol (13): ½a D27
ꢁ
ꢀ57 (c
(5S, 7S, E)-ethyl-7-(tert-butoxycarbonylamino)-7-(3,4-dimethoxyphenyl)-5-hydroxyhept-
2-enoate (7): ½a D26
ꢁ
ꢀ57 (c0.4, CHCl3); IR (KBr):
mmax 3365, 2925, 1710, 1513, 1262, 1166,
0.2, MeOH); IR (KBr): mmax 3145, 3045, 1521, 1406, 1264, 1147, 1022 cmꢀ1
;
1H
1031, 760 cmꢀ1
;
1H NMR (CDCl3, 300 MHz): d 7.03–6.90 (m, 1H), 6.80 (s, 2H), 6.76 (s,
NMR (CD3OD, 300 MHz): d 7.16 (s, 1H), 7.11–6.98 (m, 2H), 4.28 (d, J = 13.8 Hz, 1H),
4.13 (br s, 1H), 4.08–3.92 (m, 1H), 3.89 (s, 3H), 3.85 (s, 3H), 3.59 (t, J = 4.5 Hz, 2H),
2.41–2.19 (m, 2H), 1.99–1.74 (m, 2H), 1.73–1.22 (m, 6H); 13C NMR (CD3OD,
75 MHz): d 151.5, 150.8, 135.7, 121.5, 113.1, 112.5, 67.1, 62.4, 60.8, 58.0, 56.6, 46.1,
40.9, 40.3, 38.1, 33.9, 33.2, 30.9, 23.0; ESIMS: m/z 310 (M+H)+; HRMS: calcd for
C17H28NO4 (M+H)+: 310.2013, found: 310.2011.
1H), 5.86 (d, J = 15.7 Hz, 1H), 4.85(s, 2H), 4.17(q, J = 7.2 Hz, 2H), 4.10 (s, 1H), 3.88(s, 3H),
3.86 (s, 3H), 3.83–3.74 (m, 1H), 2.54–2.28 (m, 2H), 1.83–1.72 (m, 2H), 1.45 (s, 9H), 1.29
(t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 75 MHz): d 165.9, 156.6, 149.5, 145.2, 134.6, 123.7,
118.2, 111.7, 110.5, 80.2, 66.7, 60.7, 60.1, 56.0, 51.5, 45.1, 39.9, 28.6, 14.5; ESIMS: m/z
446 (M+Na)+; HRMS: calcd for C22H33NNaO7 (M+Na)+: 446.2149, found: 446.2157.
Ethyl-2-((4S,6S)-6-(3,4-dimethoxyphenyl)-4-hydroxy-piperidin-2-yl) acetate (8): ½a D26
ꢁ
:
(ꢀ)-Lasubine II (2): ½a D27
ꢁ
ꢀ41.5 (c 0.15, MeOH); IR (KBr): mmax 3356, 2924, 2854,
-31.2 (c0.3, CHCl3); IR (KBr): m ;
max 3321, 2931, 2847, 1727, 1515, 1264, 1028, 808 cmꢀ1
1736, 1461, 1370, 1266, 1150, 1026, 769 cmꢀ1
;
1H NMR (CD3OD, 300 MHz): d
1HNMR(CDCl3,300 MHz):d6.97 (s, 1H), 6.87 (d, J = 6.8 Hz,1H),6.74(d,J = 8.2 Hz, 1H),
4.57–4.52(m, 2H), 4.19(s, 1H), 4.11(q, J = 7.0 Hz, 2H), 3.87(brs, 1H), 3.86(s, 3H), 3.83(s,
3H), 3.74–3.61(m, 1H), 2.44–2.14(m, 2H), 2.07–1.77(m, 2H), 1.67–1.51 (m, 2H), 1.25(t,
J = 7.0 Hz, 3H); 13C NMR: (CDCl3, 75 MHz): d 171.8, 149.2, 148.4, 136.7, 118.9, 111.2,
110.2, 69.3, 60.4, 59.3, 55.9, 55.8, 51.6, 43.8, 41.3, 41.2, 41.0, 14.4; ESIMS: m/z 324
(M+H)+; HRMS: calcd for C17H26NO5 (M+H)+: 324.1805, found: 324.1818.
7.22–6.78 (m, 3H), 4.02 (br s,1H), 3.86 (s, 3H), 3.84 (s, 3H), 3.69–3.50 (m, 2H), 2.83
(d, J = 11.5 Hz, 1H), 2.41–2.21 (m, 1H), 1.95–1.21 (m, 12 H); 13C NMR (CD3OD,
75 MHz): d 151.8, 150.6, 137.8, 117.2, 111.8, 111.4, 65.3, 63.1, 56.5, 56.2, 55.5, 42.9,
40.1, 33.2, 26.6, 22.1; ESIMS: m/z 292 (M+H)+; HRMS: calcd for C17H25NO3 (M+H)+:
292.1907, found: 292.1918.