A stereoselective synthesis of 1,6-deoxynojirimycin by double-reductive amination of dicarbonyl sugar

Full text of DOI:10.1021/jo970826s

7482
J . Org. Chem. 1997, 62, 7482-7484
Sch em e 1
A Ster eoselective Syn th esis of
1,6-Did eoxyn ojir im ycin by
Dou ble-Red u ctive Am in a tion of Dica r bon yl
Su ga r †
Dilip D. Dhavale,* Nabendu N. Saha, and
Vijaya N. Desai
Department of Chemistry, Garware Research Center,
University of Pune, Pune 411 007, India
Received May 7, 1997
Polyhydroxylated piperidine alkaloids manifest prom-
ising therapeutic applications as antiviral agents1 and
in regulation of carbohydrate metabolic disorders.2 In
view of the particular attention on anti-HIV activity in
the AIDS area, a number of chemical and enzymatic
syntheses of deoxy aza sugars,3 in particular, 1-deoxy-
nojirimycin4 (1a ), have been reported in recent years.
However, 1,6-dideoxynojirimycin (1b) is still a somewhat
unexplored class of aza sugars in spite of their interesting
glycosidase inhibitory activity.4b Only two syntheses are
so far reported, the first approach4b involves preparation
of azido keto sugar 11 via enzymatic aldol condensation
of 3-azido-2-hydroxypropanal and dihydroxyacetone phos-
phate followed by ring closure using a palladium-
catalyzed stereocontrolled reductive amination reaction,
while the second sequence5 makes use of an asymmetric
Diels-Alder reaction of hexa-2,4-dienal O-methyloxime
with a chiral chloronitroso derivative of D-mannose
followed by osmylation to diol and nucleophilic ring
opening of cyclic sulfate. Recent efforts6 in our laboratory
directed toward the synthesis of 6-deoxynojirimycin (1c)
have led us to the development of a practical route to
1,6-dideoxynojirimycin (1b). Our approach hinges on the
double-reductive amination of suitably protected 6-deoxy-
5-keto-D-glucose, a dicarbonyl sugar, using simple reac-
tions that allow good reproducibility on a multigram scale
(Scheme 1). We have adopted this strategy because of
the vital role played by the 5-keto sugars in the biogen-
esis of nojirimycin and analogs, wherein the carbon chain
comes from D-glucose and the amino group in aza sugars
has been introduced probably using the 5-keto function-
ality.7
† Dedicated to Prof. M. S. Wadia on the occasion of his 60th birthday.
* To whom correspondence should be addressed. Fax: 0091-212-
353 899. E-mail: ddd@chem.unipune.ernet.in.
(1) (a) Karpus, A.; Fleet, G. W. J .; Dwek, R. A.; Petursson, S.;
Namgoong, S.; Ramsden, N. G.; J acob, G. S.; Rademacher, T. W. Proc.
Natl. Acad. Sci. U.S.A. 1988, 85, 9229-9233. (b) Fleet, G. W. J .;
Karpus, A.; Dwek, R. A.; Fellows, L. E.; Tyms, A. S.; Petursson, S.;
Namgoong, S. K.; Ramsden, N. G.; Smith, P. W.; Son, J . C.; Wilson,
F.; Witty, D. R.; J acob, G. S.; Rademacher, T. W. FEBS Lett. 1988,
237, 128-132. (c) Walker, B. D.; Kowalski, M.; Goh, W. C.; Kozarsky,
K.; Krieger, M.; Rosen, C.; Rohrschneider, L.; Haseltine, W. A.;
Sodroski, J . Proc. Natl. Acad. Sci. U.S.A. 1987, 84, 8120-8124. (d)
Winkler, D. A.; Holan, G. J . Med. Chem. 1989, 32, 2084-2089.
(2) (a) Paulsen, H.; Todt, K. Adv. Carbohydr. Chem. 1968, 23, 115-
232. (b) Fellows, L. E. Chem. Ber. 1987, 23, 842-844. (c) Truscheit,
E.; Frommer, W.; J unge, B.; Muller, L.; Schmith, D. D.; Wingender,
W. Angew. Chem., Int. Ed. Engl. 1981, 20, 744-761. (d) Inouye, S.;
Tsuruoka, T.; Ito, A.; Niida, T. Tetrahedron 1968, 24, 2125-2144.
(e) Muller, L. In Biotechnology; Rehn, H.-J ., Reed, G., Eds.; VCH
Verlagsgesellschaft: Weinheim, 1985; Vol. 4, Chapter 18. (f) Sinnott,
L. M. Chem. Rev. 1990, 90, 1171-1202. (g) Winchester, B.; Fleet, G.
W. J . Glycobiology 1992, 2, 199-210. (h) Wong, C.-H.; Halcomb, R.
L.; Ichikawa, Y.; Kajimoto, T. Angew. Chem., Int. Ed. Engl. 1995, 34,
412-432. (i) Wong, C.-H.; Halcomb, R. L.; Ichikawa, Y.; Kajimoto, T.
Angew. Chem., Int. Ed. Engl. 1995, 34, 521-546 and references cited
therein.
(3) For preparation of 1,5-dideoxy-1,5-imino-L-fucitol, see: (a) Ta-
kahashi, S.; Kuzuhara, H. J . Chem. Soc. Perkin Trans. I 1997, 607-
612 and references cited therein. (b) Fleet, G. W. J .; Shaw, A. N.;
Evans, S. V.; Fellows, L. E. J . Chem. Soc., Chem. Commun. 1985, 841-
842. (c) Fleet, G. W. J .; Ramsden, N. G.; Dwek, R. A.; Rademacher, T.
W.; Fellows, L. E.; Nash, R. J .; Green, D. St. C.; Winchester, B. J .
Chem. Soc., Chem. Commun. 1988, 483-485. (d) Ermet, P.; Vasella,
A. Helv. Chim. Acta 1991, 74, 2043-2047. (e) Defoin, A.; Sarazin, H.;
Streith, J . Synlett 1995, 11, 1187-1188. (f) Hammann, P. In Organic
Synthesis Highlights II; Waldmann, H., Ed.; VCH: Weinheim, 1995;
pp 323-334.
Resu lts a n d Discu ssion
Our previous report8 describes a synthesis of sugar
â-keto ester 3 by the reaction of 1,2-O-isopropylidene-3-
O-benzyl-R-D-xylo-pentodialdose (2) with ethyl diazoace-
tate in the presence of BF3-OEt2. Decarbalkoxylation9
of 3 using sodium chloride in wet DMSO afforded 5-keto
sugar 4 in good yield10 (Scheme 2). Hydrolysis of the 1,2-
O-isopropylidine functionality in 4 gave 6-deoxy-3-O-
benzyl-R-D-xylo-hexofuran-5-ulose (5). The critical double-
reductive amination reaction with benzhydrylamine,
NaCNBH3, and acetic acid in methanol at -78 °C
afforded a diastereomeric mixture of piperidines 6a ,b
corresponding to D-gluco and L-ido configurations in the
ratio 86:14, respectively. The separation of diastereomers
(4) For the preparation of 1-deoxynojirimycin, see: (a) Baxter, E.
W.; Reitz, A. B. J . Org. Chem. 1994, 59, 3175-3185 and references
cited therein. (b) Kajimoto, T.; Liu, K. K.-C.; Pederson, R. L.; Zhong,
Z.; Ichikawa, Y.; Porco, J . A., J r.; Wong, C.-H. J . Am. Chem. Soc. 1991,
113, 6187-6196 and references cited therein. (c) Kajimoto, T.; Chen,
L.; Liu, K. K.-C.; Wong, C.-H. J . Am. Chem. Soc. 1991, 113, 6678-
6680. (d) Ermet, P.; Vasella, A. Helv. Chim. Acta 1991, 74, 2043-
2047. (e) Iida, H.; Yamazaki, N.; Kibayashi, C. J . Org. Chem. 1987,
52, 3337-3342. (f) Qiao, L.; Murray, B. W.; Shimakazi, M.; Schultz,
J .; Wong, C.-H. J . Am. Chem. Soc. 1996, 118, 7653-7662. (g) Igarashi,
Y.; Ichikawa, M.; Ichikawa, Y. Bioorg. Med. Chem. Lett. 1996, 6, 553-
558. (h) Brandstetter, T. W.; Davis, B.; Hyett, D.; Smith, C.; Hackett,
L.; Winchester, B. G.; Fleet, G. W. J . Tetrahedron Lett. 1995, 36, 7511-
7514. (i) Legler, G.; Stuetz, A. E.; Immich, H. Carbohydr. Res. 1995,
272, 17-30. (j) Takahashi, S.; Kuzuhara, H. Chem. Lett. 1992, 21-
24. (k) Wong, C.-H.; Krach, T.; Narvor, C. G. L.; Ichikawa, Y.; Look,
G. C.; Gaeta, F.; Thompson, D.; Nicolau, K. C. Tetrahedron Lett. 1991,
32, 4867-4870. (l) Wong, C.-H.; Ichikawa, Y.; Krach, T.; Narvor, C.
G. L.; Dumas, D. P.; Look, G. C. J . Am. Chem. Soc. 1991, 113, 8137-
8145. (m) Liu, K. K.-C.; Kajimoto, T.; Chen, L.; Zhong, Z.; Ichikawa,
Y.; Wong, C.-H. J . Org. Chem. 1991, 56, 6280-6289.
(5) Defoin, A.; Sarazin, H.; Streith, J . Helv. Chim. Acta 1996, 79,
560-567.
(6) Dhavale, D. D.; Desai, V. N.; Sindkhedkar, M. D.; Mali, R. S.;
Castellari, C.; Trombini, C. Tetrahedron: Asymmetry 1997, 8, 1475-
1486.
(7) Hardick, D. J .; Hutchinson, D. W.; Trew, S. J .; Wellington, E.
M. H. Tetrahedron 1992, 48, 6285-6296.
(8) Dhavale, D. D.; Bhujbal, N. N.; J oshi, P.; Desai, S. G. Carbohydr.
Res. 1994, 263, 303-307.
(9) Krapcho, A. P.; J ahngen, E. G. E., J r.; Lovey, A. J . Tetrahedron
Lett. 1974, 1091-1094.
(10) Conversion of 2 to 4 via Grignard reaction using CH3MgI
followed by oxidation with PCC or J ones reagent is reported in ∼46%
overall yield; see: (a) Kiely, D. E.; Morris, P. E., J r.; J . Carbohydr.
Chem. 1990, 9, 661-673. (b) Wolfrom, M. L.; Hanessian, S. J . Org.
Chem. 1962, 27, 2107-2109. (c) Kraus, G. A.; Shi, J . J . Org. Chem.
1990, 55, 4922-4925; whereas our method, which is biomimetic, gives
68% yield. Surprisingly 4, which is the logical precursor to 1b, has
not been earlier exploited for the synthesis of aza sugars.
S0022-3263(97)00826-8 CCC: $14.00 © 1997 American Chemical Society

Notes
J . Org. Chem., Vol. 62, No. 21, 1997 7483
Sch em e 2a
Ch a r t 1
â-face attack on 10 giving information of L-ido-piperidine
(6b) still as a minor product (14%). Our results are found
to be parallel to those reported by Wong and co-workers,4b
wherein the piperidine ring closure in azido keto sugar
11 is achieved by hydrogenation under palladium-
catalyzed conditions resulting in a ∼90:10 mixture of C-5
epimers.
a
Reagents and conditions: (i) ref 8; (ii) DMSO, H2O, NaCl, 135
°C, 2 h; (iii) 3 N HCl, THF, 70 °C, 2 h; (iv) H2NCHPh2, NaCNBH3,
AcOH, MeOH, -78 °C to 20 °C, 22 h; (v) NaH, BnBr, nBu4NI, 0
to 20 °C, 5 h; (vi) HCOONH4, 10% Pd/C, MeOH, 70 °C, 30 min.
In conclusion, we have demonstrated a concise and
practical approach for the synthesis of 1,6-dideoxynojiri-
mycin (1b) by exploiting dicarbonyl sugar 4. In addition
it has been demonstrated that, in the reductive amination
process of cyclic iminium ion intermediate 10, the pres-
ence of a -CH3 group at C-5 reduces the stereodirecting
effect of hydride delivery, thus indicating that the com-
plexation with both C-4 hydroxy and C-5 methylenehy-
droxy groups is responsible for stereoselectivity in such
types of reductive amination processes.
at this stage, by flash chromatography, was troublesome
due to the close Rf values. However, benzylation of this
diastereomeric mixture with benzyl bromide and NaH
in THF afforded an easy access for purification, and the
required diastereomer 7a was isolated in good yield by
chromatography. One-pot removal of -CHPh2 and -Bn
groups in the D-gluco isomer 7a by hydrogenolysis with
ammonium formate, 10% Pd/C in methanol at 70 °C for
30 min gave 1,6-dideoxynojirimycin (1b) as a colorless
1
resin. The H- and 13C-NMR data and specific rotation
of 1b are known4b,5 and were found to be parallel with
those of the compound synthesized by us.
Exp er im en ta l Section
The observed diastereoselectivity in the double-reduc-
tive amination of 5 (86:14 D-gluco:L-ido) is intriguing in
light of results reported by Reitz and co-workers4a with
the substrate 5-keto-D-glucose (8) under identical reaction
conditions, wherein the ratio of the product obtained is
>95:5 for D-gluco and L-ido isomers, respectively. The
substrates 5 and 8, however, differ in two structural
aspects: presence of -CH3 instead of -CH2OH at C-5 and
-OBn rather than -OH at C-3 (Chart 1). It is evident that
the NaCNBH3 reductive amination reaction of cyclic
iminium ion intermediate 9 is hydroxyl directed in which
the -OH group at C-4 plays a significant stereodirecting
effect.4a The substituent at C-3 is far away from the
reactive site and therefore presumably has a lesser role
in determining the stereoselectivity of hydride addition.
Now we feel that the presence of -CH2OH at C-5, instead
of CH3, also has a stereodirecting effect of hydride
delivery. This difference in the stereoselectivity could
be ascribed to -CH2OH functionality which is oriented
in a particular fashion, probably due to intramolecular
hydrogen bonding as shown in the stereodetermining key
intermediate 9. This favors the attack of hydride from
the R-face (axial orientation) due to the complexation of
the reagent with -CH2OH and C-4 hydroxyl groups. Such
type of additional complexation effect is absent in cyclic
iminium ion 10, due to the presence of a -CH3 instead of
a CH2OH group, which might result in small access for
Gen er a l. 1H NMR (300 MHz) and 13C NMR (75 MHz) spectra
were recorded on a Varian VXR 300S spectrometer using CDCl3
and D2O as solvents. Chemical shifts are reported in ppm (δ)
relative to internal standard Me4Si, TSP. FT IR spectra were
obtained with a Perkin-Elmer 1600 spectrophotometer. Optical
rotations were measured at 25 °C with a J ASCO DIP 181
polarimeter. Elemental analyses were performed on a Hosli
carbon-hydrogen analyzer. Melting points were measured with
a Thomas Hoover capillary melting point apparatus and are
uncorrected. Whenever required the reactions were conducted
in oven-dried glassware under dry N2. On workup, the solvents
were evaporated at reduced pressure with
a Buchi rotary
evaporator. Thin layer chromatography was performed on 0.25
mm precoated silica gel polygram Sil G/UV 254. Flash chro-
matography was carried out on silica gel 230-400 mesh. All
the solvents, n-hexane, THF, diethyl ether, chloroform, metha-
nol, petroleum ether (60-80 °C), and ethyl acetate, were purified
and dried before use. Ethyl 3-O-benzyl-6-deoxy-1,2-O-isopro-
pylidene-R-D-xylo-hepto-5-ulo-furanuronate (sugar â-keto ester)
(3) was prepared from 2 in 85% yield as reported earlier.8
Benzhydrylamine, NaCNBH3, and 10% Pd/C were purchased
from Fluka.
3-O-Ben zyl-6-d eoxy-1,2-O-isop r op ylid en e-r-D-xylo-h exo-
fu r a n -5-u lose (4). A solution of sugar â-keto ester 3 (5.0 g,
13.7 mmol) and sodium chloride (0.8 g, 13.7 mmol) in DMSO
(15 mL) and water (0.5 mL) was heated at 135 °C for 2 h. After
being cooled, the reaction mixture was poured into ice-water
and extracted with ether (20 mL × 6). The combined extract
was washed with water and brine and dried over anhyd Na2-
SO4. Removal of the solvent left a residue which was purified
by chromatography using petroleum ether:ether acetate ) 19:1

7484 J . Org. Chem., Vol. 62, No. 21, 1997
Notes
to give a white solid (3.21 g, 80%): mp 54-55 °C (lit.10 mp 55-
56 °C); [R]D ) -48.0 (c 1.2, MeOH); IR (Nujol, cm-1) ν 1735,
over anhyd Na2SO4. Removal of ether gave an oil which was
purified by chromatography. Elution first with petroleum ether:
ethyl acetate ) 19:1 gave major diastereomer 7a as a pale yellow
1
1365, 1225, 1170; H NMR (CDCl3) δ 1.30 (s, 3H), 1.46 (s, 3H),
2.21 (s, 3H), 4.26 (d, J ) 2.7 Hz, 1H), 4.47 (d, J ) 11.7 Hz, 1H),
4.58 (d, J ) 13.8 Hz, 1H), 4.56-4.63 (m, 2H), 6.07 (d, J ) 2.7
Hz, 1H), 7.20-7.34 (m, 5H); 13C NMR (CDCl3) δ 26.5, 27.1, 28.5,
72.6, 82.0, 83.9, 85.7, 106.1, 112.0, 127.9, 128.3, 128.7, 137.1,
206.9. Anal. Calcd for C16H20O5: C, 65.74; H, 6.90. Found: C,
65.70; H, 6.87.
oil (1.7 g, 75%): Rf 0.70 (n-hexane:ethyl acetate ) 7:3); [R]D )
-12.56 (c 0.2, CHCl3); IR (neat, cm-1) ν 1601, 1494, 1367, 1178,
1
1069; H NMR (CDCl3) δ 1.41 (d, J ) 6.04 Hz, 3H), 1.78 (dd, J
) 11.3, 10.62 Hz, 1H), 2.38 (dq, J ) 8.79, 6.04 Hz, 1H), 3.04
(dd, J ) 11.3, 4.49 Hz, 1H), 3.22 (t, J ) 8.79 Hz, 1H), 3.39 (t, J
) 8.79 Hz, 1H), 3.63 (ddd, J ) 10.62, 8.79, 4.49 Hz, 1H), 4.53
(d, J ) 11.8 Hz, 1H), 4.58 (d, J ) 11.8 Hz, 1H), 4.61 (d, J ) 10.9
Hz, 1H), 4.76 (d, J ) 11.05 Hz, 1H), 4.94 (d, J ) 11.05 Hz, 1H),
3-O-Ben zyl-6-d eoxy-r-D-xylo-h exofu r a n -5-u lose (5).
A
solution of 4 (2.7 g, 9.2 mmol) in 3 N HCl (10 mL) and THF (20
mL) was heated at 70 °C for 2 h. After being cooled, the reaction
mixture was neutralized with saturated Na2CO3 solution to pH
7 and concentrated, and the residue was extracted with ethyl
acetate (20 mL × 5). The combined extract was dried over anhyd
Na2SO4 (twice) and ethyl acetate evaporated to give 5 as an oil
(2.1 g, 90%) which was immediately used for the next reaction.
1,5-Im in o-1,5,6-tr id eoxy-N-ben zh yd r yl-3-O-ben zyl-D-glu -
citol (6a ). To a solution of benzhydrylamine (1.22 g, 6.7 mmol)
and acetic acid (0.4 g, 6.7 mmol) in MeOH (60 mL) at -78 °C
was added 5 (2.1 g, 8.33 mmol) in MeOH (60 mL) over a period
of 30 min followed by addition of NaCNBH3 (1.05 g, 16.64 mmol)
in three portions (10 min). The mixture was stirred at -78 °C
for 2 h, allowed to warm at room temperature, and concentrated
after 20 h. Saturated aqueous Na2CO3 solution was added to
the residue, solution was extracted with CHCl3 (20 mL × 3),
and combined extract was dried over anhyd Na2SO4. Removal
of chloroform afforded a liquid that was purified by chromatog-
raphy using petroleum ether:ethyl acetate ) 9:1 to give a
diastereomeric mixture of 6a ,b as a thick oil (2.02 g, 60%). The
1H NMR indicated percentage composition of 6a :6b ) 86:14; Rf
0.66 (n-hexane:ethyl acetate ) 1:1). Diastereomer 6a : 1H NMR
δ 1.30 (d, J ) 6.4 Hz, 3H), 1.64 (bs, 1H), 2.14 (dd, J ) 11.9, 7.7
Hz, 1H), 2.52 (bs, 1H), 2.62 (dq, J ) 6.4, 6.2 Hz, 1H), 2.95 (dd,
J ) 11.9, 3.7 Hz, 1H), 3.22 (dd, J ) 6.8, 6.6 Hz, 1H), 3.46 (dd, J
) 6.6, 6.4 Hz, 1H), 3.78 (ddd, J ) 7.7, 6.8, 3.7 Hz, 1H); 4.72 (AB
4.96 (d, J ) 10.9 Hz, 1H), 5.42 (s, 1H), 7.05-7.48 (m, 25H); 13
C
NMR (CDCl3) δ 16.4, 49.31, 58.1, 64.1, 72.1, 75.1, 78.8, 79.0,
84.9, 86.7, 126.51, 127.43, 127.54, 127.59, 127.65, 127.70, 127.76,
127.86, 127.92, 127.97, 128.03, 128.08, 128.14, 128.19, 128.24,
128.30, 128.35, 128.41, 128.46, 128.51, 129.17, 130.03, 133.89,
135.11, 135.72, 141.81. Anal. Calcd for C40H41NO3; C, 82.30;
H, 7.08. Found: C, 82.08; H, 6.90.
Further elution with petroleum ether:ethyl acetate ) 17:3
afforded a mixture of diastereomer 7b and different di-O-
1
benzylated derivatives as an oil (0.31 g). The H-NMR spectrum
indicated the presence of three diastereomers as evidenced by
three methyl doublets at δ 0.98 (d, J ) 6.7 Hz, 3H), 1.18 (d, J )
6.7 Hz, 3H), 1.25 (d, J ) 6.4 Hz, 3H) in the ratio 1:1.3:1.1. Our
attempt to separate this mixture was unsuccessful.
1,5-Im in o-1,5,6-tr id eoxy-D-glu citol (1b). A solution of 7a
(1.4 g, 2.4 mmol), 10% Pd/C (3.3 g), and ammonium formate (1.06
g, 16.8 mmol) in MeOH (35 mL) was heated at 70 °C for 30 min.
The reaction mixture was brought to room temperature, the
suspension was filtered through Celite and washed with 95%
aqueous MeOH (70 mL), and the filtrate was concentrated to
give a thick viscous liquid. The residue was dissolved in water
(25 mL) and the water layer washed with CHCl3 (20 mL × 3) to
remove diphenylmethane. Lyophilization of water solution
afforded a colorless resin (0.31 g, 87%): [R]D ) +12.7 (c 0.8, H2O):
[lit.4b [R]D ) +12 (c 2.5, H2O), lit.5 [R]D ) +13 (c 1, H2O)], [R]D
)
quartet, J ) 11.7 Hz, 2H), 5.16 (s, 1H), 7.05-7.45 (m, 15H); 13
C
+10.46 (c 0.77, MeOH) [lit.5 [R]D ) +11 (c 1, MeOH)]; H NMR
(D2O) δ 1.19 (d, J ) 6.4 Hz, 3H), 2.54 (t, J ) 11.8 Hz, 1H), 2.64
(dq, J ) 9.4, 6.4 Hz, 1H), 3.07 (dd, J ) 9.9, 9.4 Hz, 1H), 3.14
(dd, J ) 11.8, 5.0 Hz, 1H), 3.30 (dd, J ) 9.9, 9.4 Hz, 1H), 3.55
(ddd, J ) 11.8, 9.4, 5.0 Hz, 1H); 13C NMR (D2O) δ 17.6, 48.9,
57.9, 70.2, 75.6, 78.9.
1
NMR (CDCl3) δ 13.6, 49.6, 57.2, 66.5, 70.1, 73.7, 74.8, 84.2, 126.8,
127.0, 127.1, 127.2, 127.3, 127.7, 127.9, 128.3, 128.6, 128.7, 129.5,
138.7, 142.6.
For diastereomer 6b, additional and detectable signals: 1H
NMR δ 0.97 (d, J ) 6.7 Hz, 3H), 2.41 (dd, J ) 1.7, 11.95 Hz,
1H), 2.78 (dd, J ) 5.5, 11.7 Hz, 1H), 4.76 (AB quartet J ) 11.0
Hz, 2H); 13C NMR δ 29.7, 48.5, 53.5, 59.8, 70.9, 71.5, 72.7, 83.9.
1,5-Im in o-1,5,6-tr ideoxy-N-ben zh ydr yl-2,3,4-tr i-O-ben zyl-
D-glu citol (7a ). A mixture of 6a ,b (1.57 g, 3.89 mmol) in THF
(12 mL) was added to NaH (0.47 g, 11.69 mmol) at 0 °C under
N2. After 10 min benzyl bromide (1.67 g, 9.74 mmol) in THF (5
mL) followed by tetrabutylammonium iodide (0.072 g, 0.195
mmol) was added. The reaction mixture was stirred at room
temperature for 5 h and poured into ice-water. Evaporation
of THF left a residue which was extracted with ether (20 mL ×
3); combined extract was washed with water and brine and dried
Ack n ow led gm en t. We are grateful to the Regional
Sophisticated Instrumentation Center, Indian Institute
of Technology, Powai, Bombay, for high-resolution NMR
spectra and to the Council of Scientific and Industrial
Research, New Delhi, for financial support. We are also
thankful to Prof. N. S. Narasimhan, Pune, for helpful
discussion.
J O970826S