Chiron approach strategy to the bicyclic oxazolidinylpiperidine: A building block for preparing mono-and bi-cyclic iminosugars

Article abstract of DOI:10.1016/j.tetlet.2011.09.039

A chiron approach to the synthesis of bicyclic oxazolidinylpiperidine, a synthetically potential building block for preparing mono-and bi-cyclic iminosugars, is reported from D-glucose using ring closing metathesis as the key step.

Full text of DOI:10.1016/j.tetlet.2011.09.039

Tetrahedron Letters 52 (2011) 6363–6365
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Chiron approach strategy to the bicyclic oxazolidinylpiperidine: a building
block for preparing mono- and bi-cyclic iminosugars
⇑
Navnath B. Kalamkar, Dilip D. Dhavale
Department of Chemistry, Garware Research Centre, University of Pune, Pune 411 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A chiron approach to the synthesis of bicyclic oxazolidinylpiperidine, a synthetically potential building
Received 4 August 2011
Revised 7 September 2011
Accepted 9 September 2011
Available online 17 September 2011
block for preparing mono- and bi-cyclic iminosugars, is reported from
metathesis as the key step.
D-glucose using ring closing
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Piperidine
Iminosugar
Carbohydrate
Glycosidase inhibitor
Chiron approach
The enantiomerically pure bicyclic oxazolidinylpiperidine 1
(Fig. 1) is endowed with unique structural features such as (i)
hydroxylated dehydropiperidine skeleton (ii) the presence of
amine and primary hydroxyl functionality in the protected cyclic
carbamate form and (iii) endocyclic C@C bond prone for cis-/
trans-dihydroxylation. These facts render 1 to act as a versatile
building block for the preparation of a variety of mono- and bi-cyc-
lic iminosugars I–IV.1–4
Iminosugars, also known as azasugars, are the polyhydroxylated
heterocyclic compounds with structural resemblance to carbohy-
drates wherein the endocyclic ring oxygen is replaced by the basic
nitrogen atom.7 Nojirimycin and its 1-deoxy analog, deoxynojiri-
mycin I, are the earliest two examples of natural iminosugars
found to exhibit potent glycosidase inhibitory activity.7a,8 Since
then much attention has been focused to discover their use in clin-
ical applications of carbohydrate-mediated diseases such as diabe-
tes, cancer, lysosomal storage disorders, and viral infections
(including HIV).9 Recently, two derivatives of these structure-
based compounds namely N-hydroxyethyl deoxynojirimycin
(Miglitol™) and N-butyl deoxynojirimycin (Zavesca™) have been
commercialized for the treatment of type II diabetes and Gaucher’s
disease, respectively.9c,d Although, a number of chiron as well as
asymmetric approaches are known for the preparation of imino-
sugars10 the development of a simple, efficient, and practical ap-
proach is still desirable. In this respect synthesis of
oxazolidinylpiperidine 1 or its derivatives and their utility in the
synthesis of different iminosugars is well established by different
research groups.1–6 For example, Ciufolini et al.2 prepared a benzyl
ether derivative of 1 from racemic furylglycine and Katsumura3
and coworkers reported its O-TBDMS derivative from (R)-4-meth-
oxycarbonyloxazolidinone which, in turn, was prepared from glyc-
idol. Riera and coworkers described an asymmetric approach
toward both enantiomers of 1 using the Sharpless asymmetric
epoxidation of (E)-2,4-pentadienol and regioselective intramolecu-
lar epoxide ring opening as key steps1a,b while; Sato as well as Lin’s
group reported chiral pool approach to 1 from D-serine in multistep
sequences.5,6 In continuation of our interest in the syntheses of
compounds11 analogous to
1
as well as iminosugars from
OH
OH
AcHN
OH
OH
HO
OH
OH
N
N
H
H
ΙΙΙ 2-N-acetyldeoxymannojirimycin
ΙΙ Deoxymannojirimycin
Ref−4
Ref−1b,3
H
H
OH
OH
OH
HO
OH
OH
N
OH
OH
Swainsonine
N
Ref−1b
H
Ref−2
N
O
H
O
Ι Λ
⇑
Corresponding author. Tel.: +91 225691727; fax: +91 20 25691728.
E-mail addresses: ddd@chem.unipune.ac.in, ddd@chem.unipune.ernet.in (D.D.
(+) or (−) 1
Ι Deoxynojirimycin
Dhavale).
Figure 1. Iminosugars from oxazolidinylpiperidine 1.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.09.039

6364
N. B. Kalamkar, D. D. Dhavale / Tetrahedron Letters 52 (2011) 6363–6365
The requisite C3 azido derivative 2 was prepared in three steps
from
-glucose as reported earlier by us and others (Scheme 2).12
H
H
H
H
OH
OH
OH
D
The one pot Staudinger reduction of the azide functionality in 2
with PPh3 in THF/water followed by N-Cbz protection using ben-
zylchloroformate and NaHCO3 furnished 313 in 90% yield. The N-
allylation of 3 using allyl bromide and sodium hydride in the pres-
ence of catalytic TBAI in THF gave N-allylated compound 4 in 96%
yield. The regioselective hydrolysis of 5,6-acetonide in 4 using 1%
H2SO4 in methanol afforded diol 5 that on reaction with PPh3, I2,
and imidazole in toluene at 70 °C provided bisalkenyl sugar deriv-
ative 6 in 80% yield (over two steps). The RCM14 of 6 with the Grub-
N
N
O
CO2Bn
O
Α
1
6
O
H
O
O
1
4 O
3
1 O
6
O
3
D
-glucose
N
2
O
H
O
N3
CO2Bn
2
Β
bs
catalyst
(first
generation)
afforded
the
requisite
Scheme 1. Retrosynthetic analysis of 1.
dehydropiperidine ring skeleton 7.15
Hydrolysis of 1,2-acetonide group in 7 under a variety of reac-
tion conditions (60% TFA/H2O, Dowex–H+, 2 N H2SO4, 30% aq
HClO4) gave a complex mixture. Therefore, we thought of an alter-
native pathway. Thus, compound 6 on hydrolysis of the 1,2-aceto-
nide functionality using 60% TFA/H2O followed by oxidative
cleavage with NaIO4 in acetone/water gave aldehyde X which
was found to be relatively unstable, and therefore immediately re-
acted with NaBH4 in methanol/H2O to afford an inseparable mix-
ture of compounds.16 This mixture was directly reacted with the
Grubbs catalyst (first generation) in CH2Cl2 at 40 °C for 5 h to give
a separable mixture of RCM products 1 and 8 in 5:2 ratio. The spec-
tral and analytical data of compound 1 were found to be in good
carbohydrates, we describe herein a new and efficient synthesis of
(+)-1 from -glucose.
D
We envisioned that, the bicyclic ring skeleton of 1 could be con-
structed from bisalkenyl diol A by ring closing metathesis (RCM)
and intramolecular carbamate formation (Scheme 1). The diol
functionality in A could be prepared from sugar-derived bisalkene
B by the sequential reaction path of 1,2-acetonide opening, cleav-
age of anomeric carbon (C1), and reduction of aldehyde. The sugar
appended bisalkene B could be synthesized from 3-azido-
D
-allose
derivative 2, obtained from
D-glucose, by usual functional group
manipulations.
agreement with that reported; ½a D25
ꢀ
+18.2 (c 1.2, CH2Cl2) [lit1b for
the antipode ½a 2D0
ꢁ16.7 (c 1.2, CH2Cl2)]. The minor product 8
ꢀ
was characterized by spectral data13 and the structure was con-
firmed by converting it into 1 using sodium hydride in THF at
0 °C. The combined yield of 1, from 6, was found to be 61% in over-
all four steps.
D
Ref. 12
O
glucose
3−steps
60% overall
In summary, we have developed an efficient strategy for the
preparation of synthetically useful chiral bicyclic oxazolidinylpi-
peridine (+)-1. The overall synthesis is straightforward and makes
use of cheap starting material/reagents under mild reaction condi-
tions. Utility of 1 in the syntheses of deoxyazasugars and antican-
cer swainsonine is known in the literature1–4 however, exploration
of 1 to the synthesis of new iminosugars and their biological eval-
uation is in progress and will be reported separately.
6
5
O
O
O
1
O
O
H
O
O
O
a
H
3
2
O
N3
BnO2C N
R
2
3 R = H
4 R = Allyl
b
c
6
HO
HO
Acknowledgments
H
O
1
O
O
4
d
e
O
H
We are grateful to Professor M. S. Wadia for helpful discussions.
We thank the Council of Scientific and Industrial Research, New
Delhi, for financial support (Project code CSIR01(2343)/09/EMR-
II) and Senior Research Fellowship to N.B.K. (CSIR award No. 09/
137(0432)/2006-EMR-I).
N
H
O
O
BnO2C N
CO2Bn
Allyl
6
5
f
H
H
O
O
OH
CHO
O
Supplementary data
N
H
N
H
CO2Bn
Supplementary data (experimental procedures and copies of 1H
and 13C NMR spectra of compounds 3–8 and 1) associated with this
Letter can be found, in the online version, at doi:10.1016/
j.tetlet.2011.09.039.
CO2Bn
Χ
7
g, h
H
H
H
OH
OH
OH
2
References and notes
6
N
H
N
O
CO2Bn
1. (a) Martin, R.; Moyano, A.; Pericas, M. A.; Riera, A. Org. Lett. 2000, 2, 93; (b)
Martin, R.; Murruzzu, C.; Pericas, M. A.; Riera, A. J. Org. Chem. 2005, 70, 2325; (c)
Murruzzu, C.; Alonso, M.; Canales, A.; Jimenez-Barbero, J.; Riera, A. Carbohydr.
Res. 2007, 342, 1805.
O
i
1
8
Scheme 2. Synthesis of 1. Reagents and conditions: (a) Ph3P, THF/H2O, rt, 30 h then
aq NaHCO3, CbzCl, rt, 5 h, 90%; (b) allyl-Br, NaH, cat TBAI, THF, 0 °C to rt, 3 h, 96%; (c)
1% aq H2SO4, MeOH, rt, 10 h, 90%; (d) PPh3, I2, Imidazole, toluene, 70 °C, 3 h, 88%; (e)
Grubbs first generation cat (10 mol %), CH2Cl2, reflux, 10 h, 70%; (f) (i) TFA/H2O
(3:2), rt, 4 h; (ii) NaIO4, acetone/H2O, rt, 1 h; (g) NaBH4, MeOH/H2O (4:1), 0 °C to rt,
1 h; (h) Grubbs first generation cat (10 mol %), CH2Cl2, 40 °C, 5 h; (i) NaH, THF, 0 °C
to rt, 45 min, overall 61% (from 6).
2. Ciufolini, M. A.; Hermann, C. Y. W.; Dong, Q.; Shimizu, T.; Swaminathan, S.; Xi,
N. Synlett 1998, 105.
3. Asano, K.; Hakogi, T.; Iwama, S.; Katsumura, S. Chem. Commun. 1999, 41.
4. AlRawi, S.; Hinderlich, S.; Reutter, W.; Giannis, A. Angew. Chem., Int. Ed. 2004,
43, 4366.
5. Shirai, M.; Okamoto, S.; Sato, F. Tetrahedron Lett. 1999, 40, 5331.
6. Subramanian, T.; Lin, C.-C.; Lin, C.-C. Tetrahedron Lett. 2001, 42, 4079.

N. B. Kalamkar, D. D. Dhavale / Tetrahedron Letters 52 (2011) 6363–6365
6365
7. (a) Stutz, A. E. Iminosugars as Glycosidase Inhibitors: Nojirimycin and Beyond, 1st
ed.; Wiley: Weinheim, Germany, 1999. p 125; (b) Lillelund, V. H.; Jensen, H. H.;
Liang, X.; Bols, M. Chem. Rev. 2002, 102, 515.
112.5 (1,2-O-isopropylidene) 116.2, 120.0 (C6/C9), 127.9 strong, 128.3 strong
(Ar), 134.1 (C5), 135.6, 136.1 (C8/Ar-C), 156.6 (NCOO). Anal. Calcd for
C20H25NO5: C, 66.83; H, 7.01; N, 3.90. Found: C, 66.92; H, 6.95; N, 4.02. Data
8. (a) Inouye, S.; Tsuruoka, T.; Ito, T.; Niida, T. Tetrahedron 1968, 24, 2125; (b)
Ishida, N.; Kumagai, K.; Niida, T.; Tsuruoka, T.; Yumoto, H. J. Antibiot., Ser. A
1967, 20, 66; (c) Daigo, K.; Inamori, Y.; Takemoto, T. Chem. Pharm. Bull. 1986, 34,
2243; (d) Iida, H.; Yamazaki, N.; Kibayashi, C. J. Org. Chem. 1987, 52, 3337.
9. For reviews on the biological activity and therapeutic applications of
iminosugars, see: (a) Horne, G.; Wilson, F. X. Prog. Med. Chem. 2011, 50, 135;
(b) Horne, G.; Wilson, F. X.; Tinsley, J.; Williams, D. H.; Storer, R. Drug Discovery
Today 2011, 16, 107; (c) Winchester, B. G. Tetrahedron: Asymmetry 2009, 20,
645; (d) Iminosugars: From Synthesis to Therapeutic Applications; Compain, P.,
Martin, O. R., Eds.; John Wiley: Chichester, UK, 2007; (e) de Melo, E. B.; Gomes,
A. D. S.; Carvalho, D. S. Tetrahedron 2006, 62, 10277; (f) Asano, N. Curr. Top. Med.
Chem. 2003, 3, 471; (g) Watson, A. A.; Fleet, G. W. J.; Asano, N.; Molyneux, R. J.;
Nash, R. J. Phytochemistry 2001, 56, 265.
10. For reviews and recent advances on syntheses of iminosugars, see: (a) Davis, B.
G. Tetrahedron: Asymmetry 2009, 20, 652; (b) Compain, P.; Chagnault, V.;
Martin, O. R. Tetrahedron: Asymmetry 2009, 20, 672; (c) Aravind, A.; Sankar, M.
G.; Varghese, B.; Baskaran, S. J. Org. Chem. 2009, 74, 2858; (d) Pandey, G.;
Dumbre, S. G.; Khan, M. I.; Shabab, M. J. Org. Chem. 2006, 71, 8481; (e) Pearson,
M. S. M.; Mathé-Allainmat, M.; Fargeas, V.; Lebreton, J. Eur. J. Org. Chem. 2005,
2159; (f) Afarinkia, K.; Bahar, A. Tetrahedron: Asymmetry 2005, 16, 1239; (g)
Ayad, T.; Genisson, Y.; Baltas, M. Curr. Org. Chem. 2004, 8, 1211; (h) Le Merrer,
Y.; Poitout, L.; Depezay, J. C.; Dosbaa, I.; Geoffroy, S.; Foglietti, M. J. Bioorg. Med.
Chem. 1997, 5, 519.
for compound (7): white solid; mp = 130–131 °C; Rf 0.4 (n-hexane/ethyl
acetate = 7:3); ½a D25
ꢀ
+110 (c 0.7, CHCl3); IR (neat): 1612 and 1703 cmꢁ1 1H
;
NMR (CDCl3); 1.25 (3H, s, CH3), 1.56 (3H, s, CH3), 2.86 (1H, dd, J = 9.3 and 3.6,
H-7a), 3.904.15 (2H, m, H-2/H-3), 4.42–4.52 (1H, m, H-7b) 4.95–5.20 (1H, m,
H-4), 5.07 (1H, d, J = 12.1, OCH2Ph), 5.30 (1H, d, J = 12.1, OCH2Ph), 5.67–5.78
(1H, m, H-6), 5.82 (1H, d, J = 2.5, H-1), 6.24 (1H, dd, J = 8.2 and 1.9, H-5), 7.22–
7.44 (5H, m, ArH); 13C NMR (CDCl3) 26.2 (CH3), 26.3 (CH3), 46.0 (C7), 61.2 (C3),
67.7 (OCH2Ph), 73.0 (C2), 78.9 (C4), 105.4 (C1), 112.4 (1,2-O-isopropylidene)
123.6 (C5), 127.7 (C6), 128.0 strong, 128.3 strong, 136.1 (Ar), 155.6 (NCOO).
Data for compound (8): Rf 0.4 (n-hexane/ethyl acetate = 1:1); ½a D25
ꢁ7.0 (c 0.5,
ꢀ
CHCl3); IR (neat): 3100–3500, 1690 and 1625–1640 cmꢁ1. The interpretation of
1H NMR spectrum of this compound was found to be difficult because of
broadening and additional signals due to presence of rotamers (due to N-Cbz
group). However, 13C NMR spectrum showed single isomer; 13C NMR (CDCl3)
41.2 (C6), 57.5 (C2), 62.6 (C1), 68.2 (OCH2Ph), 69.4 (C3), 125.0, 126.1 (C4/C5),
128.0 strong, 128.4, 128.6 strong, 135.8 (Ar), 157.8 (NCOO). Anal. Calcd for
C
14H17NO4: C, 63.87; H, 6.51; N, 5.32. Found: C, 63.97; H, 6.41; N, 5.52. Data for
compound (1): white solid; mp 85 °C; [lit.1b 86.5 °C]; Rf 0.4 (n-hexane/ethyl
acetate, 1:1); ½a D25
ꢀ
+18.2 (c 1.2, CH2Cl2) [lit.1b for the antipode ½a 2D0
ꢁ16.7 (c 1.2,
ꢀ
CH2Cl2)]; IR (KBr): 2900–3100, 1630 and 1698 cmꢁ1 1H NMR (CDCl3); 1.98–
;
2.10 (1H, br s, exchangeable with D2O, OH), 3.49 (1H, dt, J = 8.2 and 4.1, H-2),
3.63 (1H, dd, J = 18.1 and 2.6, H-6a), 4.05 (1H, dd, J = 18.1 and 2.6, H-6b), 4.13–
4.20 (1H, m, H-1a) 4.34 (1H, dd, J = 9.1 and 4.1, H-1b) 4.54 (1H, dd, J = 9.0 and
8.0, H-3) 5.735.81 (2H, br s, H-4/H-5); 13C NMR (CDCl3) 40.8(C6), 56.4 (C2),
67.3, 67.6 (C1/C3), 124.8, 130.0 (C4/C5), 157.9 (carbamate CO). Anal. Calcd for
C7H9NO3: C, 54.19; H, 5.85; N, 9.03. Found: C, 54.25; H, 5.90; N, 8.95. The 1H
NMR spectra of compounds 4, 5, 6 and 8 showed broadening of signals while,
13C NMR spectrum of compound 4 and 6 showed doubling of signals due to
presence of N-Cbz group. In NMR data of these compounds only high intensity
signals are mentioned. For the doubling/broadening of signals in NMR spectra
due the isomerisation by restricted rotation around C–N bond, see: In
Applications of NMR Spectroscopy in Organic Chemistry; Jackman, L. M.,
Sternhell, S., Eds.; Pergamon: Elmsford, NY, 1978; p 361.
11. (a) Kalamkar, N. B.; Kasture, V. M.; Dhavale, D. D. J. Org. Chem. 2008, 73, 3619;
(b) Kalamkar, N. B.; Kasture, V. M.; Dhavale, D. D. Tetrahedron Lett. 2010, 51,
6745; (c) Kalamkar, N. B.; Kasture, V. M.; Chavan, S. T.; Sabharwal, S. G.;
Dhavale, D. D. Tetrahedron 2010, 66, 8522; (d) Jabgunde, A. M; Kalamkar, N. B.;
Chavan, S. T.; Sabharwal, S. G.; Dhavale, D. D. Bioorg. Med. Chem. in press.
doi:10.1016/j.bmc.2011.07.059.
12. (a) Chaudhari, V. D.; Ajish Kumar, K. S.; Dhavale, D. D. Org. Lett. 2005, 7, 5805;
(b) Gruner, S. A. W.; Keri, G.; Schwab, R.; Venetianer, A.; Kessler, H. Org. Lett.
2001, 3, 3723; (c) Gurjar, M. K.; Patil, V. J.; Pawar, S. M. Indian J. Chem. 1987,
26B, 1115.
13. All compounds were characterized by IR, NMR (1H and 13C) and CHN
microanalysis; data for compound (3): white solid; mp = 72–73 °C; Rf 0.5 (n-
14. (a) Deiters, A.; Martin, S. F. Chem. Rev. 2004, 104, 2199; (b) Grubbs, R. H.; Miller,
S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28, 446.
hexane/ethyl acetate = 3:2); ½a D25
ꢀ
+58.3 (c 1.5, CHCl3); IR (neat); 1685 and
15. Compound 7 was found to be highly unstable and decomposed on standing.
We characterised it by spectral methods within 1 h of its preparation as it
showed developing multiple spots on TLC after 1 h. Compound 7 is known;
however, no (spectral/analytical) data is reported for the same. See: Ghosh, S.;
Shashidhar, J.; Dutta, S. K. Tetrahedron Lett. 2006, 47, 6041. We have prepared it
by different methods and characterized independently. For data see Ref. 13.
16. In this reaction, an inseparable mixture (as evident from 1H MNR) would be
due to the formation of compounds Y and Z which can be probably explained
as follows (Scheme 3). We believe that NaBH4 reduction of an aldehyde X first
results in the formation of compound Y that concomitantly undergoes partial
conversion to the 5-membered carbamate ester Z via cyclization (of primary
alcohol and N-Cbz group) initiated by in situ-generated base NaB(OMe)4
(observed reaction pH = 8) by reaction of NaBH4 and aq MeOH. On RCM
reaction of this mixture the resulted products were found to be separated by
column chromatography. For preparation of NaB(OMe)4, its basic nature and
applications as a base, see: Campana, A. G.; Fuentes, N.; GomezBengoa, E.;
Mateo, C.; Oltra, J. E.; Echavarren, A. M.; Cuerva, J. M. J. Org. Chem. 2007, 72,
8127.
3200–3500 cmꢁ1 1H NMR (CDCl3); 1.30 (6H, s, 2CH3), 1.38 (3H, s, CH3), 1.52
;
(3H, s, CH3), 3.85 (1H, dd, J = 9.3 and 4.0, H-3), 3.92 (1H, dd, J = 12.0 and 6.1, H-
6a), 3.99–4.14 (2H, m, H-5/H-4), 4.26 (1H, dd, J = 11.5 and 6.1, H-6b), 4.60 (1H,
t, J = 4.0, H-2), 5.12 (2H, AB quartet, J = 12.0, OCH2Ph), 5.21 (1H, d, J = 9.1,
exchangeable with D2O, NH), 5.80 (1H, d, J = 3.6, H-1), 7.20–7.42 (5H, m, ArH);
13C NMR (CDCl3) 25.3 (CH3), 26.3 (strong, 2CH3), 26.4 (CH3), 55.0 (C3), 65.2 (C6)
67.1 (OCH2Ph), 75.5 (C5), 78.5 (C4) 78.9 (C2), 103.9 (C1), 109.5 (5,6-O-
isopropylidene), 112.4 (1,2-O-isopropylidene) 128.0, 128.1, 128.4, 135.9 (Ar),
155.5 (NCOO). Anal. Calcd for C20H27NO7: C, 61.06; H, 6.92; N, 3.56. Found: C,
61.15; H, 7.0; N, 3.76. Data for compound (4): Rf 0.5 (n-hexane/ethyl
acetate = 3:2); ½a D25
ꢀ
+140.0 (c 1.5, CHCl3); IR (neat); 1630 and 1685 cmꢁ1 1H
;
NMR (CDCl3); 1.30 (6H, s, 2CH3), 1.38 (3H, s, CH3), 1.59 (3H, s, CH3), 3.50–3.98
(2H, m, H-7), 3.99–4.20 (3H, m, H-3/H-6), 4.21–4.38 (1H, m, H-5), 4.39–4.52
(2H, m, H-2/H-4), 4.95–5.30 (4H, m, OCH2Ph/H-9), 5.72 (1H, br s, H-1), 5.80–
6.06 (1H, m, H-8), 7.20–7.45 (5H, m, ArH); 13C NMR (CDCl3) 25.3 (CH3), 26.3
(CH3), 26.8 (CH3), 31.0 (CH3) 48.0 (C7) 59.5 (C3), 66.5 (C6) 67.6 (OCH2Ph), 75.0
(C5), 76.2 (C4), 79.8 (C2), 103.8 (C1), 109.4 (5,6-O-isopropylidene), 112.9 (1,2-
O-isopropylidene) 116.1 (C9) 127.7, 127.8, 128.0, 128.3 (Ar) 135.2, 135.5 (C8/
Ar-C), 156.7 (NCOO). Anal. Calcd for C23H31NO7: C, 63.73; H, 7.21; N, 3.23.
Found: C, 63.80; H, 7.25; N, 3.50. Data for compound (5): Rf 0.5 (n-hexane/ethyl
acetate = 4:1)½a D25
ꢀ
+41 (c 1.0, CHCl3); IR (neat): 1632, 3000–3600 cmꢁ1 1H
;
Partial
conversion
NMR (CDCl3); 1.30 (3H, s, CH3), 1.80 (3H, s, CH3), 2.45 (2H, br s, exchangeable
with D2O, OH) 3.65 (2H, br s, H-7), 3.66–4.0 (1H, m, H-3) 4.10 (2H, dd, J = 13.5
and 6.4, H-6), 4.35 (1H, dd, J = 10.2 and 4.0, H-5), 4.42–4.58 (1H, m, H-4), 4.65
(1H, br s, H-2), 5.0–5.30 (4H, m, OCH2Ph/H-9), 5.74 (1H, d, J = 2.2, H-1), 5.80–
6.0 (1H, m, H-8), 7.20–7.42 (5H, m, ArH); 13C NMR (CDCl3) 26.2 (CH3), 26.3
(CH3), 46.0 (C7), 61.2 (strong, C3/C6), 67.6 (OCH2Ph), 73.0 (C5) 77.2 (C4), 79.0
(C2), 105.4 (C1), 112.4 (1,2-O-isopropylidene) 123.6 (C9) 127.7, 128.0 strong,
128.3 strong (Ar), 128.5 (C8), 136.1, (Ar-C), 155.5 (NCOO). Anal. Calcd for
H
H
H
OH
OH
H
NaBH4
Χ
N
N
MeOH/H2O
(pH = 8)
:Β
O H
O
O
Υ
O
OBn
C
20H27NO7: C, 61.06; H, 6.92; N, 3.56. Found: C, 59.95; H, 7.02; N, 3.65. Data for
Ζ
compound (6): Rf 0.5 (n-hexane/ethyl acetate = 7:3); ½a D25
ꢀ
+167 (c 1.0, CHCl3);
Inseperable mix
Scheme 3. Mechanism for the formation of Y and Z.
IR (neat): 1630–1640 and 1690 cmꢁ1 1H NMR (CDCl3); 1.32 (3H, s, CH3), 1.60
;
(3H, s, CH3), 4.13 (2H, br s, H-7), 4.30–4.46 (1H, m, H-3) 4.63 (1H, dd, J = 10.1
and 6.8, H-2), 4.67–4.78 (1H, m, H-4), 4.98–5.12 (2H, m, H-9a/b), 5.14 (2H, s,
OCH2Ph), 5.28 (1H, d, J = 10.2, H-6a), 5.38 (1H, br d, J = 17.3, H-6b), 5.64–5.98
(3H, m, H-1/H-5/H-8), 7.22–7.42 (5H, m, ArH); 13C NMR (CDCl3) 26.2 (CH3),
26.5 (CH3), 48.0 (C7), 61.9 (C3), 67.6 (OCH2Ph), 76.1 (C2), 79.5 (C4), 103.6 (C1),