A stereodivergent approach to 1-deoxynojirimycin, 1-deoxygalactonojirimycin and 1-deoxymannojirimycin derivatives

Article abstract of DOI:10.1016/j.tetlet.2006.02.157

A stereodivergent synthesis of N-alkylated 1-deoxygalactonojirimycin and 1-deoxymannojirimycin derivatives has been achieved from a protected 1-deoxynojirimycin intermediate having two free OH groups tactically positioned at C-2 and C-4. The inversion of

Full text of DOI:10.1016/j.tetlet.2006.02.157

Tetrahedron Letters 47 (2006) 3081–3084
A stereodivergent approach to 1-deoxynojirimycin,
1-deoxygalactonojirimycin and 1-deoxymannojirimycin derivatives
Charlotte Boucheron, Philippe Compain* and Olivier R. Martin*
Institut de Chimie Organique et Analytique, UMR CNRS 6005, Universite´ d’Orle´ans, BP 6759, 45067 Orle´ans Cedex 2, France
Received 2 December 2005; revised 27 February 2006; accepted 28 February 2006
Abstract—A stereodivergent synthesis of N-alkylated 1-deoxygalactonojirimycin and 1-deoxymannojirimycin derivatives has been
achieved from a protected 1-deoxynojirimycin intermediate having two free OH groups tactically positioned at C-2 and C-4. The
inversion of configuration of the secondary alcohols was performed by way of a Swern oxidation followed by a highly diastereo-
selective reduction using NaBH4 or L-Selectride.
Ó 2006 Elsevier Ltd. All rights reserved.
Iminosugars are historically known as potent inhibitors
of glycosidases.1 Since the commercialization of the first
iminosugar-based drug in 1996 (GlysetTM, 1),2 the rate of
discoveries in the field of sugar mimetics with nitrogen
replacing the ring oxygen has increased dramatically
(Fig. 1). The scope of their biological activity has been
recently extended to the inhibition of a number of
enzymes of medicinal interest such as glycosyltrans-
ferases,3 metalloproteinases,4 a sugar nucleotide mutase,5
or nucleoside-processing enzymes.6 Consequently, a
number of potential therapeutic applications can be
envisioned.7 Iminosugars constitute promising leads
for the development of immunosuppressive,8 antiviral,9
antipsoriatic,4 antidiabetic10 and antitumour agents.7
N-Butyl 1-deoxynojirimycin (NB-DNJ, ZavescaTM, 2),
which has been approved in 2003 for the treatment of
Gaucher disease, is currently the only orally adminis-
tered drug for lysosomal glycosphingolipidoses, a rare
group of about 40 inherited diseases.11
The scope of action of iminosugars is further expanding
towards new unexpected applications: N-alkylated
derivatives of 1-deoxynojirimycin have been found
recently to reversibly induce infertility in male mice.12
In view of these recent exciting developments, efficient
approaches to iminosugar derivatives are still needed to
facilitate and accelerate the finding of new therapeutic
agents.13 We recently described a general access to noji-
rimycin C-glycosides and analogues.14 In this letter,
we wish to report the extension of this strategy to the
synthesis of N-alkyl 1-deoxyiminosugars of other confi-
gurations (D-galacto, D-manno). Since a N-alkyl chain of
at least eight carbon atoms seems to be critical for anti-
viral activity,9c,15 we first focussed on the synthesis of
N-nonyl 1-deoxygalactonojirimycin (NN-DGJ) and
N-nonyl 1-deoxymannojirimycin (NN-DMJ). Our stereo-
divergent approach hinges on the 1-deoxynojirimycin
derivative 5 having two OH groups tactically positioned
at C-2 and C-4.
The synthesis of the key diol 5 began with the nucleo-
philic substitution of mesylate 314b using neat nonyl-
amine (Scheme 1). The resulting aminosorbofuranose
derivative 4 was directly engaged in the next step
without purification. The one-pot sequence of acetal
deprotection and intramolecular reductive amination
provided the properly protected piperidine 5 with two
free OH groups at C-2 and C-4. At this stage, our syn-
thetic strategy required differentiation of the two hydr-
oxyl groups. After various attempts, highly regioselective
protection of the less hindered OH group at C-2 was
achieved using an excess of TBDMSCl and imidazole.
OH
OH
N
N
OH
HO
HO
HO
HO
OH
OH
1
2
Figure 1.
*
Corresponding authors. Tel.: +33 (0) 2 38 49 48 55; fax: +33 (0) 2 38
41 72 81; e-mail addresses: philippe.compain@univ-orleans.fr; olivier.
martin@univ-orleans.fr
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.02.157

3082
C. Boucheron et al. / Tetrahedron Letters 47 (2006) 3081–3084
O
O
O
7 steps
a
OH
( )n
L-sorbose
( )n
OBn
OBn
a
41%
N
N
MsO
b, c
OBn
OBn
HO
Ref. 14
BnO
OBn
BnO
OTBDMS
OTBDMS
3
8
6
O
O
( )n
O
4
N
c,d
b
( )n
HO
BnO
2
N
H
OBn
OH
OH
( )n
N
OBn
( )n
N
5
OH
OBn
4
BnO
BnO
HO
( )n
( )n
OBn
OH
OBn
OH
d
N
N
9
10
TBDMSO
BnO
+
HO
BnO
OTBDMS
OTBDMS
n = 7
e
7
6
n = 7
OH
OH
( )n
N
( )n
OBn
OH
Scheme 1. Reagents and conditions: (a) neat nonylamine, 90 °C, 16 h;
(b) TFA/H2O (9/1), 28 h; (c) NaBH3CN (5 equiv), AcOH (1 equiv),
MeOH, 48 h, 42% (three steps); (d) TBDMSCl (2.5 equiv), imidazole
(4 equiv), DMF, 22 h, 76% (6), 5% (7).
b
N
BnO
BnO
HO
HO
12
11
Scheme 2. Reagents and conditions: (a) (i) (COCl)2 (2.5 equiv),
DMSO (4.5 equiv), Et3N (10 equiv), CH2Cl2, ꢀ78 °C to rt, 2 h; (ii)
NaBH4 (10 equiv), MeOH, 0 °C to rt, 16 h, 77%; (b) (i) H2, Pd/C,
MeOH/HCl 5 N (10/1), 48–72 h, quant; (ii) Dowex 1-X2 (OHꢀ form);
(c) BnBr (2 equiv), NaH (3 equiv), n-Bu4NI (0.1 equiv), THF, 0 °C to
D, 6 h, 94%; (d) n-Bu4NF (3.3 equiv), THF, 7 h, 79%; (e) (i) (COCl)2
(2.5 equiv), DMSO (4.5 equiv), Et3N (10 equiv), CH2Cl2, ꢀ78 °C to rt,
2 h, brief aqueous work-up; (ii) L-Selectride (1.5 equiv), THF, ꢀ78 °C,
3 h, 64%.
After 1 day, piperidinol 6 and disilylated derivative 7
were isolated in 76% and 5% yield, respectively, after
purification on silica gel.
With iminosugar 6 in hand, we first explored the inver-
sion of configuration at C-4. The best strategy found16
was based on the two-step sequence: oxidation followed
by diastereoselective reduction.17 Under Swern condi-
tions, the tertiary amine function was not affected and
oxidation of alcohol 6 afforded the corresponding ke-
tone which was reduced in situ with sodium borohydride
(Scheme 2). This highly diastereoselective one-pot pro-
cedure18 provided alcohol 819 in 77% yield from com-
carries only one vicinal substituent (as shown, e.g., in
the NaBH4 reduction of piperidone derivatives17), and
that a larger reagent is necessary to achieve high stereo-
selectivity. Removal of the benzyl groups by hydrogen-
olysis provided the desired NN-DMJ (12).15a,25
1
pound 6 (de >98%). The H and 13C NMR parameters
established unambiguously the galacto configuration of
8. The one-step removal of the benzyl and silyl protect-
ing groups in 8 was conducted using hydrogen over pal-
ladium on carbon in MeOH/HCl 5 N (10/1) to yield
NN-DGJ (9).9c,15a,20 The high stereoselectivity of the
reduction of the intermediate 4-keto 1-deoxynojirimycin
was expected on the basis of precedents in the carbohy-
drate field. Although small hydride donors are known to
reduce simple cyclohexanone derivatives by an axial
attack as a result of fine stereoelectronic effects,21 the
reduction of cyclic hexosulosides in which the carbonyl
is flanked by two equatorial substituents has generally
given predominantly or exclusively the axial alcohol.22,23
The stereoselectivity appears here to be controlled
mainly by steric effects, which favour an equatorial
attack. By contrast, the stereoselective reduction of the
ketone derived from alcohol 10 required the use of a more
hindered hydride donor. After benzylation of the
hydroxyl group at C-4 of 6, the TBDMS group was
removed under classical conditions to provide piperidi-
nol 10 in 74% yield for the two steps. Swern oxidation
of alcohol 10 followed by reduction using L-Selectride
afforded the expected mannonojirimycin derivative
1124 in high diastereoselectivity (de >98%) (Scheme 2).
These observations are consistent with the fact that elec-
tronic factors play a more important role if the ketone
In connection with our recent studies on glycosylcer-
amide synthase inhibitors,14b we also applied this strategy
to the synthesis of original ‘iminoglycolipids’ in the
D-galacto and D-manno series. We took advantage of a
nonregioselective approach that led to the obtention of
di-alkylated iminosugars with a free hydroxyl group at
C-2 or C-4 (Schemes 3 and 4).14b We were pleased to
find that the two-step one-pot conversion of 1-deoxyno-
jirimycin derivatives 13 to their corresponding C-4
epimers 14 proceeded in high yield and high diastereo-
selectivity (Scheme 3). The benzyl groups were removed
by hydrogenolysis over palladium on carbon to afford
the 2-O,N-dialkylated 1-deoxygalactonojirimycin deriv-
atives 15 in very good yields after purification on silica
gel.
In the series of DMJ derivatives carrying a free 2-OH
group, Swern oxidation followed by L-Selectride
reduction of the crude ketone provided the expected
1-deoxymannojirimycin derivatives 17 with high diaste-
reoselectivity but in modest yields (42–45%) after purifi-
cation on silica gel.
It is noteworthy that the use of NaBH4 as a hydride
source resulted in a complete loss of stereoselectivity at

C. Boucheron et al. / Tetrahedron Letters 47 (2006) 3081–3084
3083
Acknowledgements
( )n
OBn
Financial support of this study by grants from CNRS,
from the association ‘Vaincre les Maladies Lysosomales’
and from the Agence Nationale de Recherche sur le Sida
(ANRS) is gratefully acknowledged. C.B. thanks the
French department of research for a fellowship. The
authors express their gratitude to Professor N. Asano,
for optical activity and spectral data measurements.
4 steps
a
N
O
3
HO
18-12%
BnO
Ref. 14b
( )n
n = 2 13a
n = 6 13b
OH
OH
( )n
OH
OBn
( )n
N
O
b
N
O
HO
BnO
References and notes
( )n
( )n
1. (a) Iminosugars as Glycosidase Inhibitors: Nojirimycin and
n = 2 15a
n = 6 15b
n = 2 14a
n = 6 14b
Beyond; Stutz, A. E., Ed.; Wiley-VCH: New York, 1999;
¨
(b) Asano, N.; Nash, R. J.; Molyneux, R. J.; Fleet, G. W.
J. Tetrahedron: Asymmetry 2000, 11, 1645; (c) Bols, M.;
Lillelund, V. H.; Jensen, H. H.; Liang, X. Chem. Rev.
2002, 102, 515.
Scheme 3. Reagents and conditions: (a) (i) (COCl)2 (2.5 equiv),
DMSO (4.5 equiv), Et3N (10 equiv), CH2Cl2, ꢀ78 °C to rt,
2 h 30 min; (ii) NaBH4 (10 equiv), MeOH, 0 °C to rt, 2 h, 82% (14a),
82% (14b); (b) (i) H2, Pd/C, MeOH/HCl 5N (10/1), 48 h, quant, (15a),
87% (15b); (ii) Dowex 1-X2 (OHꢀ form).
2. Mitrakou, A.; Tountas, N.; Raptis, A. E.; Bauer, R. J.;
Schulz, H.; Raptis, S. A. Diab. Med. 1998, 15, 657.
3. (a) Compain, P.; Martin, O. R. Bioorg. Med. Chem. 2001,
9, 3077; (b) Compain, P.; Martin, O. R. Curr. Top. Med.
Chem. 2003, 3, 541.
4. (a) Moriyama, H.; Tsukida, T.; Inoue, Y.; Kondo, H.;
Yoshino, K.; Nishimura, S.-I. Bioorg. Med. Chem. Lett.
2003, 13, 2737; (b) Moriyama, H.; Tsukida, T.; Inoue, Y.;
Yokota, K.; Yoshino, K.; Kondo, H.; Miura, N.;
Nishimura, S.-I. J. Med. Chem. 2004, 47, 1930.
5. (a) Lee, R. E.; Smith, M. D.; Pickering, L.; Fleet, G. W. J.
Tetrahedron Lett. 1999, 39, 8689; (b) Lee, R. E.; Smith, M.
D.; Nash, R. J.; Griffiths, R. C.; McNeil, M.; Grewal, R.
K.; Yan, W.; Besra, G. S.; Brennan, P. J.; Fleet, G. W. J.
Tetrahedron Lett. 1997, 38, 6733.
( )n
( )n
OBn
4 steps
N
a
O
BnO
3
14-8%
Ref. 14b
OH
n = 2 16a
n = 6 16b
( )n
( )n
( )
OH
N
OH
N
( )n
n
6. Schramm, V. L.; Tyler, P. C. Curr. Top. Med. Chem. 2003,
3, 525.
OH
OBn
b
O
HO
O
BnO
7. Iminosugars: Recent Insights into their Bioactivity and
Potential as Therapeutic Agents; Martin, O. R., Compain,
P., Eds.; Current Topics in Medicinal Chemistry; Ben-
tham: Hilversum, Netherlands, 2003; Vol. 3, issue 5.
8. Ye, X.-S.; Sun, F.; Liu, M.; Li, Q.; Wang, Y.; Zhang, G.;
Zhang, L.-H.; Zhang, X.-L. J. Med. Chem. 2005, 48, 3688.
n = 2 18a
n = 6 18b
n = 2 17a
n = 6 17b
Scheme 4. Reagents and conditions: (a) (i) (COCl)2 (2.5 equiv),
DMSO (4.5 equiv), Et3N (10 equiv), CH2Cl2, ꢀ78 °C to rt, 3 h, brief
aqueous work-up; (ii) L-Selectride (2 equiv), THF, ꢀ78 °C, 2 h, 45%
(17a), 42% (17b); (b) (i) H2, Pd/C, MeOH/HCl 5 N (10/1), 48 h, 34%
(18a), 62% (18b); (ii) Dowex 1-X2 (OHꢀ form).
9. See, for example: (a) Greimel, P.; Spreitz, J.; Stutz, A. E.;
¨
Wrodnigg, T. M. Curr. Top. Med. Chem. 2003, 3, 513; (b)
Robina, I.; Moreno-Vargas, A. J.; Carmona, A. T.; Vogel,
P. Curr. Drug. Metab. 2004, 5, 329; (c) Durantel, D.;
´
Branza-Nichita; Carrouee-Durantel, S.; Butters, T. D.;
Dwek, R. A.; Zitzmann, N. J. Virol. 2001, 75, 8987, and
references cited.
10. Somsak, L.; Nagy, V.; Hadazy, Z.; Docsa, T.; Gergely, P.
Curr. Pharm. Design 2003, 9, 1177.
11. (a) Butters, T. D.; Dwek, R. A.; Platt, F. M. Chem. Rev.
2000, 100, 4683; (b) Butters, T. D.; Dwek, R. A.; Platt, F.
M. Glycobiology 2005, 10, 43R.
12. (a) Van der Spoel, A. C.; Jeyakumar, M.; Butters, T. D.;
Charlton, H. M.; Moore, H. D.; Dwek, R. A.; Platt, F. M.
Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 17173; (b)
Suganuma, R.; Walden, C. M.; Butters, T. D.; Platt, F.
M.; Dwek, R. A.; Yanagimachi, R.; Van der Spoel, A. C.
Biol. Reprod. 2005, 72, 805.
C-2, the D-gluco and D-manno products 16 and 17 being
obtained as an equimolar mixture after the reaction. In
this case, the carbonyl group, which has only one vicinal
equatorial substituent, is less hindered than at C-4 and
axial attack of NaBH4 is not prevented. Deprotection
of 17 by hydrogenolysis under acidic conditions afforded
the free 4-O,N-dialkylated 1-deoxymannojirimycin
derivatives 18.
In conclusion, we have described a practical stereodiver-
gent approach for the preparation of iminohexitols
related to DNJ of biological interest by way of the
highly stereoselective reduction of piperidones. Future
work will focus on the extension of this strategy to other
series such as D-allo or D-talo to prepare rare iminosu-
gars. Investigations on the activity of the synthesized
glycomimetics as carbohydrate-processing enzyme
inhibitors are in progress and will be reported in due
course.
13. For recent reviews on the synthesis of iminosugars, see: (a)
Afarinkia, K.; Bahar, A. Tetrahedron: Asymmetry 2005,
´
16, 1239; (b) Pearson, M. S. M.; Mathe-Allainmat, M.;
Fargeas, V.; Lebreton, J. Eur. J. Org. Chem. 2005, 2159;
(c) Cipolla, L.; La Ferla, B.; Nicotra, F. Curr. Top. Med.
Chem. 2003, 3, 485.
14. (a) Godin, G.; Compain, P.; Masson, G.; Martin, O. R. J.
Org. Chem. 2002, 67, 6960; (b) Boucheron, C.; Desver-

3084
C. Boucheron et al. / Tetrahedron Letters 47 (2006) 3081–3084
HRMS (ESI) m/z 584.4133 [M+H]+ (C35H58NO4Si
gnes, V.; Compain, P.; Martin, O. R.; Lavi, A.; Mackeen,
M.; Wormald, M. R.; Dwek, R. A.; Butters, T. D.
Tetrahedron: Asymmetry 2005, 16, 1747.
requires 584.4135).
20. Selected data for iminoalditol 9: 1H NMR (500 MHz,
CD3OD): d 0.90 (br t, 3H); 1.22–1.36 (m, 12H); 1.49 (m,
2H); 2.11 (t, 1H, J = 10.5 Hz, H-1ax.); 2.37 (br t, 1H, H-
5); 2.48 (m, 1H, NCH2); 2.70 (m, 1H, NCH2); 2.98 (dd,
1H, J = 5.5, 10.5 Hz, H-1eq); 3.20 (dd, 1H, J = 4.0,
10.0 Hz, H-3); 3.80 (m, 3H, H-6, H-2); 3.97 (m, 1H, H-
4); 13C NMR (125 MHz, CD3OD): d 14.5; 23.8; 25.1; 28.7;
30.5; 30.7; 30.8; 33.1; 54.1; 58.1; 62.4; 65.3; 69.1; 72.2; 77.3;
15. (a) Mehta, A.; Conyers, B.; Tyrrell, D. L. J.; Walters, K.-A.;
Tipples, G. A.; Dwek, R. A.; Block, T. M. Antimicrob.
Agents Chemother. 2002, 46, 4004; (b) Pavlovic, D.; Neville,
D. C. A.; Argaud, O.; Blumberg, B.; Dwek, R. A.; Fischer,
W.; Zitzmann, N. Proc. Natl. Acad. Sci. U.S.A. 2003, 100,
6104.
16. Displacement of a triflate leaving group via SN2 reaction
led to untractable mixtures of products. These results may
be due to the nucleophilic character of the endocyclic
amine, which causes side reactions.
20
½aꢁD +5.0 (c 0.16, MeOH); HRMS (FAB) m/z 290.2328
[M+H]+ (C15H32NO4 requires 290.2331).
21. For a discussion of the general preference for axial or
equatorial hydride delivery to cyclohexanones, see: (a) Wu,
Y.-D.; Tucker, J. A.; Houk, K. N. J. Am. Chem. Soc. 1991,
113, 5018, and references cited; (b) Carey, F. A.; Sundberg,
R. A. In Advanced Organic Chemistry. Part A: Structure
and Mechanisms, 4th ed.; Springer: New York, 2000.
22. Chang et al. have recently reported a systematic study
concerning the stereoselective reduction of ketosugars
(hexosuloses): Chang, C.-W. T.; Hui, Y.; Elchert, B.
Tetrahedron Lett. 2001, 42, 7019, and references cited.
23. See, for example: Kondo, Y.; Kashimura, N.; Onodera, K.
Agric. Biol. Chem. 1974, 38, 2553.
17. (a) Jourdant, A.; Zhu, J. Tetrahedron Lett. 2000, 41, 7033;
(b) Ciufolini, M. A.; Hermann, C. W.; Whitmire, K. H.;
Byrne, N. E. J. Am. Chem. Soc. 1989, 111, 3473; (c)
´
Badorrey, R.; Cativila, C.; Dıaz-de-Villegas, M. D.;
´
Galvez, J. A. Tetrahedron 2002, 58, 341; (d) Shirude, P.
S.; Kumar, V. A.; Ganesh, K. N. Tetrahedron 2004, 60,
9485.
18. Typical experimental procedure: To a solution of oxalyl
chloride (74 lL, 0.85 mmol) in anhydrous dichlorometh-
ane (2 mL) was added DMSO (107 lL, 1.5 mmol) under
argon. The solution was stirred at ꢀ78 °C for 30 min. A
solution of alcohol 6 (195 mg, 0.33 mmol) in anhydrous
dichloromethane (5 mL) was then added. After 3 h at
ꢀ78 °C, Et3N (467 lL, 3.35 mmol) was added and the
reaction mixture was warmed to room temperature and
stirred for 2 h. A solution of NaBH4 (127 mg, 3.35 mmol)
in MeOH (6 mL) was then added at 0 °C and the reaction
mixture was stirred at room temperature for 16 h. The
crude mixture was evaporated to dryness and then taken
into AcOEt (20 mL). The solution was washed with water
(20 mL) and saturated aqueous NaCl (20 mL). The
organic layer was dried (MgSO4) and concentrated under
reduced pressure. Purification on silica gel (petroleum
ether/ethyl acetate 6/1) afforded the secondary alcohol 8 as
a colourless oil (151 mg, 77%).
24. Selected data for iminoalditol 11: 1H NMR (250 MHz,
CDCl3): d 0.88 (br t, 3H); 1.24–1.41 (m, 14H); 2.37 (br d,
2H, H-1ax., H-5); 2.57 (m, 1H, NCH2); 2.72 (m, 1H,
NCH2); 2.97 (dd, 1H, J = 4.4, 12.2 Hz, H-1eq.); 3.41 (dd,
1H, J = 3.1, 8.8 Hz, H-3); 3.62 (dd, 1H, J = 2.2, 10.4 Hz,
H-6A); 3.68 (dd, 1H, J = 3.1, 10.4 Hz, H-6B); 3.81 (t, 1H,
J = 8.8, H-4); 3.99 (m, 1H, H-2); 4.45 (m, 3H, OCH2Ph);
4.64 (d, 1H, J = 11.6 Hz, OCH2Ph); 4.73 (d, 1H,
J = 11.9 Hz, OCH2Ph); 4.90 (d, 1H, J = 11.0 Hz,
OCH2Ph); 7.20–7.37 (m, 15H, 3 C6H5); 13C NMR
(62.9 MHz, CDCl3): d 14.2; 22.8; 24.8; 27.6; 29.4; 29.6;
29.7; 32.0; 52.7; 55.1; 64.0; 65.4; 66.6; 71.5; 73.3; 75.2; 76.1;
83.7; 127.6; 127.7; 127.8; 128.0; 128.1; 128.4; 128.5; 138.2;
20
138.4; 138.8; ½aꢁD ꢀ9.0 (c 0.7, CHCl3); HRMS (ESI) m/z
19. Selected data for iminoalditol 8: 1H NMR (250 MHz,
CDCl3): d 0.09 (s, 6H); 0.90 (m, 12H); 1.14–1.43 (m, 14H);
2.14 (t, 1H, J = 10.7 Hz, H-1ax.); 2.44 (m, 2H, H-5,
NCH2); 2.66 (m, 1H, NCH2); 2.89 (dd, 1H, J = 5.0,
11.3 Hz, H-1eq.); 3.12 (dd, 1H, J = 3.1, 8.8 Hz, H-3); 3.69
(m, 2H, H-6); 4.00 (m, 2H, H-2, H-4); 4.46 (d, 1H,
J = 11.6 Hz, OCH2Ph); 4.53 (d, 1H, J = 11.9 Hz,
OCH2Ph); 4.68 (s, 2H, OCH2Ph); 7.24–7.38 (m, 10H,
2C6H5); 13C NMR (62.9 MHz, CDCl3): d ꢀ4.7; ꢀ4.5;
14.2; 18.1; 22.7; 24.2; 25.9; 27.5; 29.3; 29.6; 29.7; 31.9; 52.9;
57.7; 62.3; 68.9; 70.4; 72.2; 73.5; 83.5; 127.6; 127.7; 127.8;
560.3740 [M+H]+ (C36H50NO4 requires 560.3740).
25. Selected data for iminoalditol 12: 1H NMR (500 MHz,
CD3OD): d 0.89 (br t, 3H); 1.24–1.36 (m, 12H); 1.47 (m,
2H); 2.11 (m, 1H, H-5); 2.48 (dd, 1H, J = 1.5, 12.5 Hz, H-
1ax); 2.58 (m, 1H, NCH2); 2.74 (m, 1H, NCH2); 2.97 (dd,
1H, J = 4.0, 12.5 Hz, H-1eq.); 3.29 (dd partly masked by
the signal of methanol, 1H, J = 4.0 Hz, H-3); 3.65 (t, 1H,
J = 9.5 Hz, H-4); 3.82 (m, 1H, H-2); 3.87 (m, 2H, H-6);
13C NMR (125 MHz, CD3OD): d 14.5; 23.8; 25.3; 28.7;
30.4; 30.74; 30.77; 33.1; 54.0; 56.6; 59.2; 67.0; 69.66; 69.71;
20
76.7; ½aꢁD ꢀ40.5 (c 0.5, MeOH); HRMS (FAB) m/z
20
128.3; 128.4; 137.9; 138.5; ½aꢁD +6.5 (c 0.6, CHCl3);
290.2333 [M+H]+ (C15H32NO4 requires 290.2331).