Practical synthesis of 2,6-dideoxy-D-lyxo-hexose ('2-deoxy-d-fucose') from D-galactose

Article abstract of DOI:10.1016/S0008-6215(98)00160-8

2,6-Dideoxy-D-lyxo-hexose was prepared efficiently from D-galactose in eight steps (25% overall yield). The synthesis is amenable to multigram scale-up. Copyright (C) 1998 Elsevier Science Ltd.

Full text of DOI:10.1016/S0008-6215(98)00160-8

Carbohydrate Research 310 (1998) 223±228
Practical synthesis of 2,6-dideoxy-d-lyxo-hexose
(``2-deoxy-d-fucose'') from d-galactose
Cynthia M. Shafer, Tadeusz F. Molinski *
Department of Chemistry, University of California, Davis, California, 95616, USA
Received 4 February 1998; accepted 10 June 1998
Abstract
2,6-Dideoxy-d-lyxo-hexose was prepared eciently from d-galactose in eight steps (25% overall
yield). The synthesis is amenable to multigram scale-up. # 1998 Elsevier Science Ltd. All rights
reserved
Keywords: 2-Deoxy-d-fucose; Synthesis; d-Galactose; d-Fucose; Oliose
1. Introduction
yield) [14] and now required the d- form 2 for nat-
ural product synthesis. While the common natu-
rally occurring form of fucose is l- (derived from
kelp polysaccharide [15]), d-fucose is rare and pro-
hibitively expensive as a starting material for pre-
paration of 2.1 We describe here a convenient
preparation of 1 from d-galactose (3, ꢀ$80/kg)
that takes place by two-step protection of C-1,3,4
OH groups, sequential deoxygenation of the 2,6-
OH groups, and deprotection (Scheme 1). The
procedure is economical, amenable to multigram
scale-up and proceeds through the useful di€eren-
tially-protected 2-deoxy-d-fucose derivative, 2.
2,6-Dideoxy-d-lyxo-hexose (1, 2-deoxy-d-fucose,
oliose) and its methyl ethers occur as glycosides in
natural products; for example the olivomycin anti-
tumor-antibiotics [1±7], the cardenolide glycoside
adigoside [8], and polyketide glycosides, phenelfa-
mycins [9]. Sugar 1 is not commercially available,
despite the desirability for its incorporation into
natural product syntheses. Syntheses have been
reported for dl-1 [10], and 1 [11±13], but in general
they involve starting materials or reagents that are
not amenable to large-scale preparation. For
example, the Roush synthesis, beginning with 6-
hepten-3-yn-2-ol, required kinetic resolution by
Sharpless asymmetric epoxidation and gave 1 in
seven steps (overall yield, 18±20%) [12]. Recently,
we reported a short synthesis of the 2-deoxy-l-
fucose derivative, ent-2, from l-fucose (3 steps, 59%
2. Results and discussion
Conversion of d-galactose (3) into the benzyl
glycopyranoside 4 (8:1 ꢀ:ꢁ anomers) was achieved
in two steps (BnOH, HCl [16]; 2,2-dimethoxy-
propane, p-TSA [17], 69% overall yield, Scheme 1
(for 1H NMR data, see Table 1). Deoxygenation of
the C-6 hydroxyl could be e€ected by standard
methods (selective 6-O-tosylation followed by
* Corresponding author. Fax:+1-530-752-8995; e-mail:
tfmolinski@ucdavis.edu
1
l- and d-Fucose are priced at $350/500 g and $4500/
100 g, respectively (Pfanstiehl Laboratories, Inc.).
0008-6215/98/$Ðsee front matter # 1998 Elsevier Science Ltd. All rights reserved
PII S0008-6215(98)00160-8

224
C.M. Shafer, T.F. Molinski/Carbohydrate Research 310 (1998) 223±228
Scheme 1. (a), i BnOH, HCl 4, 72%, ii 2,2-dimethoxypropane, p-TSA, then Et3N, MeOH: H2O, 96%; (b), PhSSPh, n-Bu3P, THF,
Á, 86% (73% a anomer); (c), Ra-Ni, EtOH, Á, 91%; (d), NaH, CS2, CH3l, imidazole, THF, 96%; (e), H3PO2, Et3N, AlBN Á,
diox, 77%; (f), Na, NH3 (l), THF, 33, 92%; (g), Ca, NH3 (l), THF, 33, 70%; (h), Dowex 50X (H+), THF-H2O, 90%.
Table 1
1H NMR data of compounds 1, 2, 6±8
1
300 MHz H NMR, CDCl3 (ꢀ-pyranose): ppm (mult., J Hz)
Compound
i-Pr
H-1
H-2
H-3
H-4
H-5
H-6
1.19
(d, 6.5)
1.26
1a
2
Ð
5.34 (bd, 3.5)
1.81 (bdd, 14.0, 5.5)
1.87 (ddd, 14.0, 12.0, 3.5) (ddd, 12.0, 5.5, 3.5) (bd, 3.5)
1.80 (ddd, 14.9, 6.3, 4.0)
2.22 (ddd, 14.9, 5.1, 4.9)
3.82 (ddd, 7.0b, 6.5, 3.9)
4.07
3.68
4.12
(bq, 6.5)
3.92
1.34 (s) 5.02 (dd, 6.3, 5.1)
1.49 (s)
1.36 (s) 4.94 (d, 3.9)
1.52 (s)
1.36 (s) 5.17 (d, 3.6)
1.54 (s)
1.35 (s) 5.34 (ddd, 7.1, 5.3) 1.72 (ddd, 15.1, 7.1, 3.5)
1.48 (s) 2.25 (ddd, 15.1, 5.3, 4.4)
4.48
(ddd, 7.1, 4.9, 4.0)
4.23
(dd, 6.5, 6.0)
4.55
(dd, (8.1, 5.2)
4.46
(ddd, 7.2, 4.4, 3.5)
3.98
(dd, 7.1, 2.0) (qd, 6.5, 2.0) (d, 6.5)
4.06 4.16 1.31
(dd, 6.0, 2.2) (qd 6.7, 2.2) (d, 6.7)
4.13 4.21 1.37
(dd, 5.2, 2.5) (qd 6.6, 2.5) (d, 6.6)
3.96 3.84 1.26
(dd, 7.2, 2.0) (qd, 6.3, 2.0) (d, 6.3)
6
7
5.76 (dd, 8.1, 3.6)
8
a
Recorded in D2O, 500 MHz, mixture of pyranose and furanose anomers, ꢂ given for ꢀ-pyranose.
Coupling to OH.
b
iodide displacement and catalytic hydrogenolysis)
[18], however, attempts to remove both C-2 and C-
6 hydroxyl groups simultaneously using this
method gave poor yields due to sluggish rates of
displacement reactions at the more-hindered C-2
position. It was found that C-2,6 deoxygenation
was more conveniently adapted to large-scale
throughput (ꢀ50 g) by stepwise reductive cleavage.
Compound 4 was converted into the anomeric 6-S-
phenyl-6-thio glycosides 5a,b (PhSSPh, n-Bu3P,
THF, re¯ux, 86%, 5:1 ratio, respectively) from
which the major ꢀ anomer 5a could be isolated by
fractional crystallization and chromatography
(73%). We have carried out the latter transformation
on scales of up to ꢀ70 g without diculty.
Although the 5a,b mixture was successfully con-
verted into 2, it was more convenient to carry
through with crystalline 5a. Compound 5a was
desulfurized with Raney-Ni (EtOH, re¯ux, 91%) to
give the d-fucose derivative 6. Conversion of 6 into
the corresponding 2-xanthate ester 7 (NaH, CS2,
cat. imidazole, then MeI, 96%) and subsequent
reduction was achieved by the Barton±McCombie
reaction, using bu€ered hypophosphorous acid
(AIBN, H3PO2, aqueous, Et3N, dioxane, re¯ux)
[19] to a€ord 2 in 77% yield from 7. The use of the
inexpensive, aqueous soluble hydrogen donor
H3PO2 gave an improved yield over standard

C.M. Shafer, T.F. Molinski/Carbohydrate Research 310 (1998) 223±228
225
reducing conditions (n-Bu3SnH in re¯uxing
toluene) and avoided the dicult and often tedious
removal of Sn byproducts associated with stannane
reductions [19].
alternative when Naꢁ±NH3 (l) and catalytic
hydrogenation are unsuitable.
Deprotection of the 1-O-benzyl group of 2
proved to be dicult without incurring over-
reduction. Attempts at debenzylation by catalytic
hydrogenolysis (Pearlman's catalyst, Pd(OH)2±C,
EtOH, 1 or 4 atm; Pd-C, EtOH, 1±4 atm; Pd-C,
NH4HCOO±MeOH) were sluggish or gave
variable, low yields of 8, perhaps due to poisoning
of catalyst by trace sulfur impurities in 2. Heating
the substrate in the presence of Raney-Ni (EtOH,
re¯ux) prior to attempted debenzylation improved
the yield of 8 only slightly, while dissolving alkali
metalꢁ reduction (Liꢁ or Naꢁ in liquid ammonia,
33 C) gave the over-reduced alditol 9 (92%).
While debenzylation of benzyl hexopyranosides
with Naꢁ±NH3 has been reported [20], the 2-deoxy
sugar 8 appeared to be particularly sensitive to
overreduction. We were pleased to ®nd that
replacement of Naꢁ with Caꢁ (5 equiv, NH3 (l),
33ꢁ, 0.75 h) allowed ecient cleavage of the O-Bn
group to a€ord 8 (4.5:1 ꢀ:ꢁ anomers) in good yield
(70%), with little over-reduction. Although of Caꢁ-
NH3(l) has been used for reductive removal of pri-
mary O-Bn ethers [21], to our knowledge, this is
the ®rst application to debenzylation of anomeric
1-O-Bn sugar derivatives.
Completion of the synthesis was achieved by
hydrolysis of the acetonide group in 8 (Dowex
50X2, H+ form, THF±H2O) to give pure 2,6-
dideoxy-d-lyxo-hexopyranose (1, 90%, [ꢀ]d +55ꢁ,
c 0.61, H2O, equil).2 The 1H and 13C NMR spectra
of 1 (D2O) were in excellent agreement with
published values [10] [12] and con®rmed that 1
exists mainly in the pyranose form (ꢀ90%, ꢀ:ꢁ
anomers 1:1.2 ratio) with about 10% of the fur-
anose tautomers.
In summary, we have completed an ecient
synthesis of 1 from galactose in eight steps, with a
25% overall yield (21% from 5a) and an average
yield per step of 85%. The synthesis is amenable to
large-scale throughput using relatively inexpensive
reagents. Finally, ecient hydrogenolytic cleavage
of the benzyl glycoside 2 in high yield with Caꢁ in
liquid NH3 allows debenzylation without over-
reduction and demonstrates the latter as a useful
3. Experimental
General procedures.ÐAll solvents were dried and
distilled from glass prior to use. In particular, THF
and 1,4-dioxane were dried and distilled from Naꢁ±
benzophenone ketyl. Melting points are uncor-
rected. Optical rotations were measured on a Jasco
DIP 370 polarimeter and H NMR and 13C NMR
1
spectra were recorded on a General Electric QE
300 (300 MHz and 75 MHz, respectively) or GE
Omega 500 NMR spectrometers (500 and 125 MHz
respectively). Unless otherwise stated, chemical
1
shifts are referenced as follows. H; ꢂ 0.00 ppm,
(Me4Si in CDCl3 or sodium 4,4-dimethy-4-sila-
pentanoate in D2O), and 13C; ꢂ 77.00 ppm for the
center peak of CDCl3 or ꢂ 66.5 ppm for 1,4-diox-
ane in D2O. 13C multiplicities (CH3, CH2, CH and
C) were deduced from DEPT experiments. Mass
spectra were obtained on several instruments at the
University of California, Riverside, Mass
Spectrometry facility and elemental analyses were
provided by Midwest Microlabs (Indianapolis,
IN). Chromatography was carried out on silica gel
(43±63 mm, EM Merck).
Benzyl 6-deoxy-3,4-O-isopropylidene-6-S-phenyl-
6-thio-d-galactopyranoside (5).ÐCompound 4 [23]
(31.43 g, 0.10 mol) in THF (300 mL) was added to a
solution of tri-n-butylphosphine (64 mL, 0.26 mol)
and diphenyl disul®de (48.03 g, 0.26 mol) in THF
ꢁ
at 0 C. After stirring at room temperature for
27.5 h, the solvent was remove in vacuo to give a
yellow oil that was puri®ed by vacuum ¯ash chro-
matography (silica gel; hexane to 3:7 ethyl acetate±
hexane) to give a white solid (35.17 g, 86%). The ꢀ
anomer 5a was puri®ed by crystallization (EtOAc±
hexane) and silica gel chromatography (73%), mp
ꢁ
103±104 C; [ꢀ]d+80.6ꢁ (c 5.03, CHCl3); Rf0.35
(1:1 EtOAc±hexane); UV (MeCN) 257 (" 8767),
1
328 nm (" 49); H NMR (300 MHz, CDCl3) ꢂ 1.31
(s, 3 H), 1.49 (s, 3 H), 2.45 (bs, 1 H), 3.24 (m, 2 H,
H-6), 3.83 (m, 1 H), 4.15 (m, 1 H), 4.23 (m, 2 H),
4.48 (d, 1 H, J 11.5 Hz, CH2Ph), 4.74 (d, 1 H, J
11.5 Hz, CH2Ph), 4.94 (d, 1 H, J 3.8 Hz, H-1), 7.29
(m, 10 H); 13C NMR (CDCl3) ꢂ 25.7 (CH3), 27.5
(CH3), 34.2 (CH2), 67.3 (CH), 69.0 (CH), 69.4
(CH2), 73.6 (CH), 75.8 (CH), 96.4 (CH), 109.5 (C),
126.1 (CH), 127.9 (CH), 128.2 (2ÂCH), 128.4
(2ÂCH), 129.0 (2ÂCH), 129.1 (2ÂCH), 136.0 (C),
Lit. values [ꢀ]d+48.8ꢁ, c 1.0, H2O, equil) [12], +55.5ꢁ
2
(no solvent given) [11], +51ꢁ (c 0.9, H2O) [3]. For ent-1,
[ꢀ]d 51.5ꢁ (c, 1.0, H2O, equil) [22].

226
C.M. Shafer, T.F. Molinski/Carbohydrate Research 310 (1998) 223±228
136.8 (C); HREIMS found m/z 402.1505 (M+),
C22H26O5S requires 402.1501; Anal. Calcd for
C22H26O5S: C, 65.65; H, 6.52; S, 7.95. Found: C,
65.57; H, 6.42; S, 7.97; ꢁ anomer (5b) Rf 0.31 (1:1
evaporated in vacuo to give 7 as a yellow oil
(4.3774 g, 96%). ꢀ anomer: mp 67±68 ꢁC; 1H NMR
(see Table 1): 13C NMR (CDCl3) ꢂ 16.0 (CH3), 18.7
(CH3), 26.3 (CH3), 27.8 (CH3), 63.6 (CH), 69.8
(CH2), 73.2 (CH), 76.3 (CH), 80.0 (CH), 94.7
(CH), 109.2 (C), 127.4 (2ÂCH), 127.6 (CH), 128.2
(2ÂCH), 137.2 (C), 215.8 (C); ꢁ anomer: 13C NMR
(CDCl3) ꢂ 16.4, 19.2, 26.3, 27.5, 68.8, 69.7, 76.5,
76.9, 80.9, 98.4, 110.2, 127.3, 127.5, 128.2, 137.0,
215.7. HRCIMS found m/z 385.1150 (MH+),
C18H25O5S2 requires 385.1177; Anal. Calcd for
C18H24O5S2: C, 56.23; H, 6.29; S, 16.68. Found: C,
55.92; H, 6.25; S, 16.51.
1
EtOAc±hexane); H NMR (300 MHz, CDCl3) ꢂ
1.29 (s, 3 H), 1.51 (s, 3 H), 2.24 (bs, 1 H, OH),
3.34 (dd, 1 H, J 13.4, 6.7 Hz, H-6), 3.38 (dd, 1 H, J
13.4, 6.7 Hz, H-6), 3.60 (dd, 1 H, J 8.5, 7.2 Hz, H-
2), 3.79 (ddd, 1 H, J 6.7, 6.7, 2.1 Hz, H-5), 4.00
(dd, 1 H, J 7.2, 5.5 Hz, H-3), 4.16 (d, 1 H, J
8.5 Hz, H-1), 4.19 (dd, 1 H, J 5.5, 2.1 Hz, H-4),
4.58 (d, 1 H, J 11.6 Hz, CH2Ph), 4.88 (d, 1 H, J
11.6 Hz, CH2Ph), 7.34 (m, 10 H).
Benzyl
6-deoxy-3,4-O-isopropylidene-6-d-gal-
Benzyl 2-deoxy-3,4-O-isopropylidene-a-d-lyxo-
hexo-pyranoside (2).ÐBenzyl 3,4-O-isopropyl-
idene-2-O-[(S-methylthio)thiocarbonyl]-ꢀ-d-galacto-
pyranoside (7, 1.5160 g, 3.95 mmol) was dissolved
in 1,4-dioxane (20 mL). Freshly distilled Et3N
(5.4 mL, 38.7 mmol) was added, and the solution
was deoxygenated by passage of a ®ne stream of
N2 for 10 min. Hypophosphorous acid (2.0 mL of a
50% aqueous solution, 19.3 mmol) was deox-
ygenated separately and then added to the above
solution. An aliquot of degassed AIBN (0.1 eq, in
1,4-dioxane) was added to the solution, and the
actopyranoside (6).ÐRaney nickel (W-2, Acros,
aqueous suspension) was resuspended and
decanted from absolute EtOH (3Â) before use.
Portions of the Raney Ni±EtOH suspension were
added to a stirred solution of benzyl 6-deoxy-
3,4-O-isopropylidene-6-S-phenyl-6-thio-ꢀ-d-galacto-
pyranoside (5, 23.78 g, 59.2 mmol) in absolute
EtOH (200 mL) at re¯ux over a period of 7 h until
the reduction was complete (TLC). The suspension
was cooled, ®ltered through Celite, the ®lter pad
washed with EtOH and combined ®ltrates con-
centrated in vacuo to a yellow oil (17.2 g). The
crude material was puri®ed by column chromato-
graphy (4.5 cmÂ15 cm, 2:3 to 3:7 EtOAc±hexane)
to give 6 as a clear oil (15.79 g, 91%). Rf 0.62
(EtOAc); HRCIMS found m/z 295.1546 (MH+),
ꢁ
¯ask was immersed in a 100 C oil bath. After 1 h,
TLC indicated that the starting material had been
consumed. The reaction was cooled, and H2O
(15 mL) was added. The aqueous layer was extrac-
ted with CH2Cl2, dried over MgSO4, and evapo-
rated in vacuo to a yellow oil. The crude material
was puri®ed by column chromatography (silica gel;
4.5Â25 cm; 1:19 to 2:3 EtOAc±hexane) to give the
product 2 as a yellow oil (0.8501 g, 77%); ꢀ
anomer: [ꢀ]d +80.2ꢁ (c 1.0, CHCl3); Rf 0.45 (3:7
EtOAc±hexane); 1H NMR (see Table 1); 13C NMR
(CDCl3) ꢂ 16.0 (CH3), 25.3 (CH3), 26.7 (CH3), 30.5
(CH2), 64.5 (CH), 68.9 (CH2), 70.6 (CH), 75.1
(CH), 95.7 (CH), 108.6 (C), 127.4 (CH), 127.6
(2ÂCH), 128.3 (2ÂCH), 138.2 (C); HREIMS
found m/z 278.1524 (M+), C16H22O4 requires
278.1518. ꢁ anomer: [ꢀ]d 41.3ꢁ (c 1.0, CHCl3);
13C NMR (CDCl3) ꢂ 16.9 (CH3), 26.4 (CH3), 28.2
(CH3), 35.3 (CH2), 68.8 (CH), 69.9 (CH2), 72.3
(CH), 74.0 (CH), 98.0 (CH), 109.1 (C), 127.6 (CH),
127.9 (CH), 128.2 (CH), 137.4 (C).
1
C16H22O5 requires 295.1545; ꢀ anomer: H NMR
(see Table 1). 13C NMR (CDCl3) ꢂ 16.0 (CH3), 25.7
(CH3), 27.5 (CH3), 64.0 (CH), 69.2 (CH), 69.5
(CH2), 75.5 (CH), 75.9 (CH), 96.9 (CH), 108.9 (C),
127.7 (CH), 128.2 (CH), 137.3 (C); ꢁ anomer: 13C
NMR (CDCl3) ꢂ 16.5 (CH3), 26.3 (CH3), 28.2
(CH3), 69.3 (CH), 70.7 (CH2), 73.7 (CH), 76.4
(CH), 79.0 (CH), 101.2 (CH), 109.8 (C), 127.9
(CH), 128.2 (CH), 128.4 (CH), 137.2 (C).
Benzyl 3,4-O-isopropylidene-2-O-[(S-methylthio)-
thiocarbonyl]-a-d-galactopyranoside (7).ÐBenzyl
3,4-O-isopropylidene-6-deoxy-6-phenylthio-ꢀ-d-
galactopyranoside (6, 3.493 g, 11.9 mmol) was dis-
solved in THF (30 mL) and added to hexane-
washed NaH (0.53 g±80% dispersion in oil,
17.7 mmol) in THF (30 mL). Imidazole (0.0122 g,
0.18 mmol) was added, and then after 2 h, CS2
(3.0 mL, 49.9 mmol) was added. After another 2 h,
MeI (3.0 mL, 48.2 mmol) was added. Forty-®ve
min later the mixture was poured into 10 mL of
H2O. The aqueous layer was extracted three
times with CH2Cl2, dried through MgSO4, and
2,6-Dideoxy-3,4-O-isopropylidene-d-lyxo-hexose
(8).ÐCalcium turnings (0.0806 g, 2.01 mmol) were
added to anhydrous liquid NH3 (200 mL, distilled
from NaNH2). A solution of benzyl 2-deoxy-3,4-
O-isopropylidene-ꢀ-d-lyxo-hexopyranoside (2,
0.1121 g, 0.40 mmol) in THF (1±0 mL) was added

C.M. Shafer, T.F. Molinski/Carbohydrate Research 310 (1998) 223±228
227
to the blue solution. After 40 min, reaction quen-
ched by addition of solid NH4Cl. The mixture was
diluted with THF and stirred while immersed in a
warm water bath until the NH3 had evaporated.
Filtration through MgSO4 and concentration in
vacuo gave a yellow oil (0.1135 g). Column chro-
matography (1.5Â15 cm; 3:7 EtOAc±hexane) gave
8 as a clear oil (52.5 mg; 70%) consisting of a mix-
ture of anomers (4.5:1 ꢀ:ꢁ). [ꢀ]d +10.3ꢁ (c 3.5,
CHCl3); Rf 0.20 (1:1 EtOAc±hexane); IR (NaCl,
neat) 3440 (OH), 1460 cm ; ꢀ anomer: H NMR,
(see Table 1); 13C NMR (CDCl3) ꢂ 16.1 (CH3), 25.1
(CH3), 26.5 (CH3), 30.8 (CH2), 64.9 (CH), 70.6
(CH), 75.1 (CH), 90.4 (CH), 108.7 (C), ꢁ anomer ꢂ
16.5 (CH3), 25.1 (CH3), 26.5 (CH3), 33.8 (CH2),
and passed through a syringe ®lter (Nalgene,
0.2 mm, 25 mm cellulose acetate) with subsequent
removal of water to a€ord 1 as clear glass (31.2 mg,
90%); [ꢀ]d +55ꢁ (c 0.61, H2O, equil); Rf 0.05 (1:9
EtOH±CH2Cl2); 1H NMR (500 MHz, D2O)
showed a mixture of tautomeric forms: pyranose
(90%, ꢀ:ꢁ 1:1.2) and furanose (10%), ꢂ were
identical with literature values [11] [12]; ꢀ pyr-
1
anose; H NMR, (see Table 1); 13C NMR (D2O,
ꢀ/ꢁ pyranose, only) ꢂ 15.8/16.0 (CH3), 31.6/34.5
(CH2), 64.7/66.4 (CH), 68.0/69.4 (CH), 70.4/70.8
(CH), 91.3/93.5 (CH); HRCIMS found m/z
166.1084 (M+NH4+), C6H16NO4 requires
166.1079.
1
1
68.3 (CH), 72.0 (CH), 74.9 (CH), 93.2 (CH), 108.7
+
(C); HRCIMS found m/z 188.1284 [(M+NH4
H2O)+], C9H18O3N requires 188.1287.
±
Acknowledgements
2,6-Dideoxy-3,4-O-isopropylidene-d-lyxo-hexitol
(9).ÐHexane-washed lithium (0.270 g, 38.9 mmol)
was added to anhydrous liquid NH3 (300 mL, dis-
tilled from NaNH2). A solution of benzyl 2-deoxy-
3,4-O-isopropylidene-ꢀ-d-lyxo-hexopyranoside (2,
0.9707 g, 3.48 mmol) in 20 mL THF was added and
after 40 min the reaction was quenched by addition
of solid NH4Cl. The mixture was diluted with THF
and stirred while the ¯ask was immersed in a warm
water bath until the NH3 had evaporated. Filtra-
tion of the mixture through MgSO4 and con-
centration in vacuo gave a yellow oil (0.8303 g).
Column chromatography (4.5Â18 cm; 1:1 EtOAc±
hexane to EtOAc) gave 9 as a clear oil (0.6077 g;
92%); [ꢀ]d +16.9ꢁ (c 0.55, CHCl3); Rf 0.09 (1:1
The authors thank Je€ DeRopp for 500 MHz 1H
NMR measurements on 1. This research was fun-
ded by the National Institutes of Health (AI 31660
and AI 39987). The 500 MHz NMR spectrometer
was partially funded through NIH ISIO-RR04795
and NSF BBS88-04739.
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1
EtOAc±hexane); IR (NaCl, neat) 3420 (OH) cm ;
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6.2 Hz, H-6), 1.38 (s, 3 H), 1.50 (s, 3 H), 1.69 (m, 1
H, H-2), 1.90 (m, 1 H, H-2), 2.59 (bs, 2 H, OH),
3.82 (m, 3 H), 3.90 (dd, 1 H, J 6.3, 5.9 Hz), 4.33
(ddd, 1 H, J 10.9, 5.9, 2.8 Hz); 13C NMR (CDCl3) ꢂ
19.6 (CH3), 25.4 (CH3), 27.8 (CH3), 31.9 (CH2),
60.6 (CH2), 65.6 (CH), 75.5 (CH), 81.6 (CH), 108.3
(C); HRCIMS found m/z 191.1287 (MH+),
C9H19O4 requires 191.1283.
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water. Volatile solvent was removed by rotary
evaporation and the remaining aqueous solution
was lyophilized. The residue was dissolved in H2O
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