Synthesis of a carbon analogue of N-acetylmannosamine via acetolysis on a relatively stable ozonide

Article abstract of DOI:10.1021/jo020362k

After a 2-methylpropenyl group was added to a carbohydrate framework through regioselective opening of a glucose-derived epoxide, hydrolysis or acetolysis of the methyl glycoside in various derivatives was problematic. Ozonolysis of the olefin followed by brief treatment with dimethyl sulfide gave a mixture of diastereomeric ozonides that proved to be stable for weeks at room temperature. Acetolysis of these ozonides at low temperature allowed selective cleavage of the methyl glycoside in the presence of the 1,2,4-trioxolane as well as selective formation of the α-acetate.

Full text of DOI:10.1021/jo020362k

Syn th esis of a Ca r bon An a logu e of
N-Acetylm a n n osa m in e via Acetolysis on a
Rela tively Sta ble Ozon id e
Liqiang Chen and David F. Wiemer*
Department of Chemistry, University of Iowa,
Iowa City, Iowa 52242-1294
david-wiemer@uiowa.edu
Received May 31, 2002
Abstr a ct: After a 2-methylpropenyl group was added to a
carbohydrate framework through regioselective opening of
a glucose-derived epoxide, hydrolysis or acetolysis of the
methyl glycoside in various derivatives was problematic.
Ozonolysis of the olefin followed by brief treatment with
dimethyl sulfide gave a mixture of diastereomeric ozonides
that proved to be stable for weeks at room temperature.
Acetolysis of these ozonides at low temperature allowed
selective cleavage of the methyl glycoside in the presence of
the 1,2,4-trioxolane as well as selective formation of the
R-acetate.
F IGURE 1.
olefin and a series of deprotections. Compound 4 in turn
might be obtained from the known epoxide 5 if an
appropriate nucleophile were used to open the epoxide
and the equatorial orientation of the C-3 hydroxyl group
in compound 4 could be secured.
In the actual synthesis, epoxide 5 was prepared by a
one-flask procedure in which commercially available
methyl glucoside 6 was treated with tosyl chloride in the
presence of base followed by cyclization under phase-
transfer catalysis conditions (Scheme 1).9 When treated
with the Grignard reagent derived from 3-chloro-2-
methylpropene, epoxide 5 was opened regioselectively in
almost quantitative yield to give methyl glycoside 7 with
the expected D-altro configuration.10 Inversion of the C-3
hydroxyl group was accomplished through an oxidation-
reduction sequence. The free hydroxyl group of compound
7 was oxidized through a Swern procedure10 to give
ketone 8 in excellent yield. The desired reduction of this
ketone would require an attack of hydride from the â face,
but previous studies have shown that in similar ketones
reduction with NaBH4 results in preferred attack from
the â face.11 However, Fraser-Reid and co-workers have
found that hydride attack might be reversed in orienta-
tion if DIBAL were used.12 When these conditions were
applied to ketone 8, the desired isomer 4 was obtained
as the major product in a 6:1 ratio along with the C-3
epimer 7.
Ozonolysis is an important method for conversion of
alkenes into ketones and aldehydes. A generally accepted
mechanism involves initial formation of an unstable
primary ozonide that undergoes cycloreversion and sub-
sequent cycloaddition to give a more stable secondary
ozonide.1 The resulting ozonides usually are reduced to
ketones or aldehydes without isolation,2 but recently,
there has been increased interest in direct transforma-
tions in which ozonides serve as precursors for com-
pounds other than carbonyl compounds.3-5 In this paper,
we wish to report isolation of unusually stable carbohy-
drate-derived ozonides and a novel acetolysis reaction to
cleave the methyl glycosidic bond in the presence of the
ozonide. 6
In connection with studies on the elasticity of sialic acid
biosynthesis, we became interested in carbon analogues
of N-acetylmannosamine (1, Figure 1). In the target
compound 2 and its peracetylated derivative 3, the ni-
trogen atom is formally replaced with a methylene group,
resulting in a ketone in place of the amide functional
group. If compound 2 or 3 could enter the sialic acid
biosynthesis pathway and be incorporated into cell sur-
face glycoconjugates, the ketone group presumably could
be detected through reaction with biotin hydrazide.7,8
In our synthetic approach, it was envisioned that the
branched sugars 2 or 3 could be obtained from the methyl
mannoside derivative 4 after oxidative cleavage of the
The olefin 4 could serve as a precursor for the needed
ketone moiety in the target compounds through a se-
quence involving cleavage of the methyl glycosidic bond
followed by ozonolysis of the alkene. Alternatively, the
double bond could be converted to a ketone group first
(6) Taken in part from the Ph.D. Thesis of Liqiang Chen, University
of Iowa, 2002.
(1) (a) Kuczkowski, R. L. Chem. Soc. Rev. 1992, 21, 79-83. (b)
Criegee, R. Angew. Chem. 1975, 87, 7937.
(7) Mahal, L. K.; Yarema, K. J .; Bertozzi, C. R. Science 1997, 276,
1125-1128.
(8) Lee, J . H.; Baker, T. J .; Mahal, L. K.; Zabner, J .; Bertozzi, C. R.;
Wiemer, D. F.; Welsh, M. J . J . Biol. Chem. 1999, 274, 21878-21884.
(9) Szeja, W. Carbohydr. Res. 1988, 183, 135-139.
(10) Wood, A. J .; Holt, D. J .; Dominguez, M.-C.; J enkins, P. R. J .
Org. Chem. 1998, 63, 8522-29.
(11) Hanessian, S.; Rancourt, G. Pure Appl. Chem. 1977, 49, 1201-
1214.
(12) Yu, K. L.; Handa, S.; Tsang, R.; Fraser-Reid, B. Tetrahedron
1991, 47, 189-204.
(2) Lee, D. G.; Chen, T. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 7, pp
544-558.
(3) Hon, Y.-S.; Lu, L.; Chang, R.-C.; Lin, S.-W.; Sun, P.-P.; Lee, C.-
F. Tetrahedron 2000, 56, 9269-9279.
(4) Fleming, F. F.; Huang, A.; Sharief, V. A.; Pu, Y. J . Org. Chem.
1999, 64, 2830-2834.
(5) Hon, Y.-S.; Lin, S.-W.; Lu, L.; Chen, Y.-J . Tetrahedron 1995, 51,
5019-5034.
10.1021/jo020362k CCC: $22.00 © 2002 American Chemical Society
Published on Web 09/25/2002
J . Org. Chem. 2002, 67, 7561-7564
7561

SCHEME 1
SCHEME 2
NMR signals at ∼108 and ∼94 ppm, values that are
consistent with literature values of similar ozonides.16
While no effort was taken to separate the two isomers,
formation of diastereomers was reasonable given the
chiral environment imposed by the carbohydrate motif.
The isolated ozonides 12 proved to be surprisingly
stable, with no apparent decomposition after 6 weeks at
room temperature, as judged by both 1H and 13C NMR
experiments, and both satisfactory HRMS and analytical
data were obtained. To compare ozonides 12 with the
analogous ketone, sugar 11 was treated with potassium
osmate and sodium periodate to give ketone 10 in almost
quantitative yield. The NMR spectra of ketone 10 were
substantially different from those of ozonides 12. Most
notably, the ketone carbonyl carbon of compound 10 was
observed at 206 ppm in the 13C NMR spectrum.
When ozonides 12 were subjected to acetolysis under
dilute conditions18 at -25 °C, the reaction proceeded
slowly. After 24 h, compound 13 was isolated in 70% yield
as a 1.5:1 mixture of two diastereomers (Scheme 3),
indicating that the 1,2,4-trioxolane was relatively stable
under these conditions while the methyl glycoside was
more reactive. Because the diastereomeric ratio did not
differ from that of compound 12, it would be reasonable
to assume that the two diastereomers originated from
the 1,2,4-trioxolane stereochemistry instead of the C-1
position of the sugar ring. For this reason, the R orienta-
tion was assigned to C-1 in compound 13. Both the
greater reactivity of the methyl glycoside and selective
formation of the R anomer could be rationalized by a
transition state19 where a trioxolane oxygen stabilizes a
positive charge at the anomeric position while shielding
the â-face from an approaching nucleophile.
and the protecting group then removed to furnish the
target compound 2. To examine the first approach,
various acetolysis conditions (Ac2O and H2SO4,13 Ac2O
and FeCl3,14 and Ac2O and Tf2O15) were applied to
attempt conversion of compound 4 into the acetylated
derivative 9. Unfortunately, each of these conditions
produced a complex mixture based on TLC analysis.
When acidic hydrolysis of methyl glycoside 4 was ex-
plored, the glycosidic methyl group could not be removed
without compromise of the olefin, based on 1H NMR
analysis of the resulting mixture.
The limited success of this approach encouraged efforts
to convert the olefin into a ketone prior to attempting
hydrolysis. Ozonolysis of olefin 4 and subsequent reduc-
tive workup gave the corresponding ketone in low yield.
When this ketone was subjected to mild acidic hydrolysis
and subsequent acetylation, the acetylated methyl gly-
coside 10 (Scheme 2) was isolated in very low yield along
with a complex mixture of other carbohydrate derivatives
including both furanose and pyranose forms of the
carbohydrate.
After these attempts at cleaving the glycosidic bond
went unrewarded, a more stepwise approach was ex-
plored. Removal of the benzylidene group in sugar 4
under mild acidic conditions followed by acetylation
produced the acetylated methyl glycoside 11 in 83%
overall yield (Scheme 2) without significant loss of the
olefin. Sugar 11 was treated with ozone and then with
dimethyl sulfide for 6 h at room temperature. Surpris-
ingly, a 1.5:1 mixture of the diastereomeric ozonides 12
was obtained after flash column chromatography, which
may be due in part to the low reactivity of dimethyl
sulfide.17 Each of these two compounds exhibited 13C
When the acetolysis of compound 12 was conducted at
0 °C, a mixture of compound 13 and the corresponding
ketone 14 was obtained in a ratio of ∼2.5:1. However,
the target compound 14 could be obtained more efficiently
(16) (a) Boddy, I. K.; Cambie, R. C.; Rutledge, P. S.; Woodgate, P.
D. Aust. J . Chem. 1986, 39, 2075-2088. (b) Griesbaum, K.; Hilss, M.;
Bosch, J . Tetrahedron 1996, 52, 14813-14826.
(17) Kostova, K.; Dimitrov, V.; Simova, S.; Hesse, M. Helv. Chim.
Acta 1999, 82, 1385-1399.
(18) Erbeck, S.; Liang, X.; Krieger, R.; Prinzbach, H. Eur. J . Org.
Chem. 1998, 481-492.
(19) McPhail, D. R.; Lee, J . R.; Fraser-Reid, B. J . Am. Chem. Soc.
1992, 114, 1905-1906.
(13) Kaczmarek, J .; Preyss, M.; Lo¨nnberg, H.; Szafranek, J . Carbo-
hydr. Res. 1995, 279, 107-16.
(14) Dasgupta, F.; Singh, P. P.; Srivastava, H. Carbohydr. Res. 1980,
80, 346-349.
(15) Angibeaud, P.; Utille, J .-P. J . Chem. Soc., Perkin Trans. 1 1990,
1490-1492.
7562 J . Org. Chem., Vol. 67, No. 21, 2002

saturated NaHCO3, and brine and then dried over Na2SO4 and
filtered. The filtrate was concentrated and purified by flash
column chromatography (15-25% EtOAc/hexanes) to give com-
pound 710 as a white solid (120 mg, 12%) and compound 4 as a
clear syrup that solidified after standing at rt (736 mg, 75%):
SCHEME 3
mp 69-71 °C; [R]24 +27.7 (c 1.02, CHCl3); 1H NMR (400 MHz,
D
CDCl3) δ 7.52-7.45 (m, 2H), 7.41-7.32 (m, 3H), 5.56 (s, 1H),
4.83 (s, 1H), 4.75 (s, 1H), 4.61 (s, 1H), 4.30-4.22 (m, 2H), 3.84-
3.74 (m, 2H), 3.63 (dd, J ) 9.4, 9.4 Hz, 1H), 3.34 (s, 3H) 2.56 (d,
J ) 14.2 Hz, 1H), 2.35 (ddd, J ) 12.0, 5.7, 1.7 Hz, 1H), 2.07 (dd,
J ) 14.3, 12.1 Hz, 1H), 1.74 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 143.7, 137.3, 129.2, 128.3 (2C), 126.2 (2C), 112.3, 102.2, 101.2,
79.7, 69.0, 67.5, 63.1, 54.9, 42.3, 32.4, 22.2. Anal. Calcd for
C18H24O5: C, 67.48; H, 7.55. Found: C, 67.24; H, 7.79.
Meth yl 3,4,6-Tr i-O-a cetyl-2-d eoxy-2-(2-m eth yla llyl)-R-D-
m a n n op yr a n osid e (11). A solution of compound 4 (1.01 g, 3.16
mmol) in a mixture of MeOH (32 mL), water (3.2 mL), and TFA
(2.1 mL) was allowed to stir at rt for 3 h. The reaction mixture
was diluted with EtOAc, washed with saturated NaHCO3, water,
and brine, and then dried (Na2SO4) and filtered. The filtrate was
concentrated and dried in vacuo to give a white solid. After the
solid was dissolved in anhydrous pyridine (20 mL), acetic
anhydride (1.80 mL, 19.1 mmol) was added dropwise. The
mixture was allowed to stir at rt for 24 h and concentrated. After
the resulting residue was dissolved in EtOAc and washed with
1 N HCl, saturated NaHCO3, and brine, the organic layer was
dried (Na2SO4) and filtered. The filtrate was concentrated, and
the resulting residue was purified by flash column chromatog-
raphy (25% EtOAc/hexanes) to give compound 11 as a clear
syrup (940 mg, 83%): [R]24D +46.2 (c 1.18, CHCl3); 1H NMR (400
MHz, CDCl3) δ 5.37 (dd, J ) 9.8, 5.5 Hz, 1H), 5.12 (dd, J ) 9.9,
9.9 Hz, 1H), 4.82 (s, 1H), 4.74 (s, 1H), 4.63 (s, 1H), 4.20 (dd, J )
12.2, 5.1 Hz, 1H), 4.14 (dd, J ) 12.1, 2.5 Hz, 1H), 3.92 (ddd, J )
10.0, 5.0, 2.5 Hz, 1H), 3.36 (s, 3H), 2.45 (dddd, J ) 11.1, 5.4,
3.6, 1.7 Hz, 1H), 2.30 (dd, J ) 14.4, 2.60 Hz, 1H), 2.17 (dd, J )
14.4, 11.2 Hz, 1H), 2.10 (s, 3H), 2.04 (s, 3H), 2.03 (s, 3H), 1.69
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.6, 169.9, 169.8, 142.4,
112.6, 100.3, 70.9, 68.1, 66.4, 62.7, 55.0, 40.4, 33.2, 22.2, 20.8,
20.7 (2C); HRFABMS calcd for C17H26O8Na (M + Na)+ 381.1525,
found 381.1530. Anal. Calcd for C17H26O8: C, 56.97; H, 7.31.
Found: C, 57.01; H, 7.38.
from ozonides 13 by reduction of the 1,2,4-trioxolane ring
to the desired ketone.2,20-23 When ozonides 13 were
treated with 3.3 equiv of dimethyl sulfide at room
temperature, only ∼50% completion was observed even
after 10 days. After an additional 13.2 equiv of dimethyl
sulfide was added, complete reaction was observed after
10 more days and the target compound 14 was obtained
as a single isomer, presumably the R isomer, in 86% yield.
In contrast, when compounds 13 were treated with zinc/
acetic acid,23 the starting material was consumed in 30
min and the target compound 14 was obtained as a single
isomer in 94% yield. The 1H NMR spectra of the products
from both reductions were identical.
In conclusion, the target ketone 14 was obtained from
the commercially available methyl glucoside 6 through
chemical transformations including regioselective open-
ing of epoxide 5, stereoselective reduction of ketone 8,
and most notably, selective acetolysis of ozonides 12. The
NMR data of the final product were in agreement with
those very recently reported by Bertozzi and co-workers
for material prepared by a different route.24 This confirms
that the product reported here is indeed the R isomer and
highlights the utility of the unusually stable ozonide 12
as a control element during acetolysis.
Met h yl 2-Acet on yl-3,4,6-t r i-O-a cet yl-2-d eoxy-R-D-m a n -
n op yr a n osid e (10). Compound 11 (305 mg, 0.85 mmol) was
dissolved in a mixture of THF (6 mL) and water (6 mL). A
solution of sodium periodate and potassium osmate dihydrate
in water (3 mL) was added dropwise, and the mixture was
allowed to stir at rt for 2 h. After addition of water (5 mL), the
mixture was extracted with EtOAc. The combined organic
extract was washed with
1 N NaHSO3, water, saturated
NaHCO3, and brine and then dried (Na2SO4) and filtered. The
filtrate was concentrated, and the residue was purified by flash
column chromatography (50% EtOAc/hexanes) to give compound
10 as a clear syrup that solidified after standing at rt (304 mg,
99%): mp 64-66 °C; [R]28D +49.3 (c 1.02, CHCl3); 1H NMR (400
MHz, CDCl3) δ 5.45 (dd, J ) 9.9, 5.5 Hz, 1H), 5.03 (dd, J ) 10.0,
10.0 Hz, 1H), 4.58 (s, 1H), 4.24 (dd, J ) 12.2, 5.1 Hz, 1H), 4.09
(dd, J ) 12.2, 2.3 Hz, 1H), 3.93 (ddd, J ) 10.0, 5.1, 2.3 Hz, 1H),
3.37 (s, 3H), 2.93-2.86 (m, 1H), 2.82 (dd, J ) 18.3, 3.9 Hz, 1H),
2.59 (dd, J ) 18.3, 9.4 Hz, 1H), 2.19 (s, 3H), 2.11 (s, 3H), 2.03
(s, 3H), 1.99 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 205.9, 170.6,
170.0, 169.5, 100.9, 69.6, 67.8, 66.6, 62.6, 55.1, 39.2, 38.1, 30.3,
20.8, 20.7, 20.6; HRFABMS calcd for C16H24O9Na (M + Na)+
383.1318, found 383.1310. Anal. Calcd for C16H24O9: C, 53.31;
H, 6.72. Found: C, 53.10; H, 6.76.
Met h yl 3,4,6-Tr i-O-a cet yl-2-d eoxy-2-C-((3-m et h yl-1,2,4-
t r ioxola n -3-yl)m et h yl)-R-D-m a n n op yr a n osid e (12). Com-
pound 11 (609 mg, 1.70 mmol) was dissolved in anhydrous
CH2Cl2 (30 mL) and cooled to -78 °C. Ozone was bubbled
through the solution for 15 min, and the resulting blue solution
was flushed with argon until it was clear. Dimethyl sulfide (0.20
mL, 2.7 mmol) was added, and the reaction mixture was allowed
to warm to rt and stirred at rt for 6 h. The mixture was diluted
with CH2Cl2, washed with 1 N HCl and then with saturated
NaHCO3, and dried (Na2SO4). After filtration, the filtrate was
Exp er im en ta l Section
Met h yl 4,6-O-Ben zylid en e-2-d eoxy-2-(2-m et h yla llyl)-R-
D-m a n n op yr a n osid e (4). To a solution of compound 810 (971
mg, 3.05 mmol) in anhydrous THF (12 mL) at 0 °C was added
DIBAL (1.0 M in THF, 18.3 mL, 18.3 mmol) over 20 min. After
the addition was complete, the mixture was allowed to warm to
rt. After the reaction mixture was stirred at rt for 2 h, the
mixture was cooled to 0 °C and water (5 mL) was added slowly.
The resulting gel was dissolved with 1 N HCl and extracted with
EtOAc. The combined organic layer was washed with 1 N HCl,
(20) Pappas, J . J .; Keaveney, W. P.; Gancher, E.; Berger, M.
Tetrahedron Lett. 1966, 4273-78.
(21) Lorenz, O.; Parks, C. R. J . Org. Chem. 1976, 30, 1976-1981.
(22) Turner, R. B.; Mattox, V. R.; McGuckin, W. F.; Kendall, E. C.
J . Am. Chem. Soc. 1976, 30, S 1952, 74, 5814-18.
(23) Iwata, C.; Takemoto, Y.; Doi, M.; Imanishi, T. J . Org. Chem.
1988, 53, 1623-1628.
(24) J acobs, C.; Goon, S.; Yarema, K. J .; Hinderlich, S.; Hang, H.
C.; Chai, D. H.; Bertozzi, C. R. Biochemistry 2001, 40, 12864-12874.
J . Org. Chem, Vol. 67, No. 21, 2002 7563

concentrated and the residue was purified by flash column
chromatography (35% EtOAc/hexanes) to give ozonide 12 as a
clear syrup (493 mg, 71%) consisting of a 1.5:1 mixture of two
diastereomers: 1H NMR (400 MHz, CDCl3) δ 5.34 (dd, J ) 10.0,
5.5 Hz, 0.6H), 5.31 (dd, J ) 9.1, 5.5 Hz, 0.4H), 5.14 (s, 0.6H),
5.12 (s, 0.4H), 5.06 (s, 0.6H), 5.05 (s, 0.4H), 4.99 (dd, J ) 10.1,
10.1 Hz, 0.4H), 4.98 (dd, J ) 10.1, 10.1 Hz, 0.6H), 4.80 (d, J )
1.1 Hz, 0.6H), 4.76 (d, J ) 1.1 Hz, 0.4H), 4.22 (dd, J ) 12.2, 5.1
Hz, 0.6H), 4.21 (dd, J ) 12.2, 5.0 Hz, 0.4H), 4.10 (dd, J ) 12.2,
2.4 Hz, 1H), 3.90 (ddd, J ) 10.0, 5.1, 2.4 Hz, 1H), 3.37 (s, 3H),
2.61-2.54 (m, 0.4H), 2.54-2.47 (m, 0.6H), 2.20-2.12 (m, 0.6H),
2.12-2.07 (m, 3.4H), 2.06-1.86 (m, 7H), 1.44 (s, 1.2 H), 1.43 (s,
1.8H); 13C NMR (100 MHz, CDCl3, major isomer) δ 170.6, 169.9,
169.8, 109.1, 101.6, 94.3, 70.2, 67.8, 66.4, 62.6, 55.1, 38.3, 31.7,
23.3, 20.9, 20.7, 20.7; HRFABMS calcd for C17H26O11Na (M +
Na)+ 429.1373, found 429.1371. Anal. Calcd for C17H26O11: C,
50.23; H, 6.45. Found: C, 50.44; H, 6.57.
1,3,4,6-Tetr a -O-a cetyl-2-d eoxy-2-C-((3-m eth yl-1,2,4-tr iox-
ola n -3-yl)m eth yl)-R-D-m a n n op yr a n ose (13). To a solution of
ozonide 12 (266 mg, 0.65 mmol) and acetic anhydride (0.10 mL,
1.1 mmol) in anhydrous CH2Cl2 (7 mL) at -25 °C was added 1
M sulfuric acid in anhydrous CH2Cl2 (0.37 mL). The resulting
mixture was allowed to stir at -25 °C for 24 h, and then
saturated NaHCO3 was added. After it had warmed to rt, the
mixture was diluted with EtOAc, washed with water and brine,
and then dried (Na2SO4). After filtration, the filtrate was
concentrated and the residue was purified by flash column
chromatography (40% EtOAc in hexanes) to give ozonide 13 as
a clear syrup (198 mg, 70%) consisting of a 1.5:1 mixture of two
diastereomers: 1H NMR (400 MHz, CDCl3) δ 6.29 (d, J ) 1.5
Hz, 0.6H), 6.19 (d, J ) 1.5 Hz, 0.4H), 5.36 (dd, J ) 10.1, 5.4 Hz,
0.6H), 5.33 (dd, J ) 10.0, 5.4 Hz, 0.4H), 5.16-5.03 (m, 3H), 4.21
(dd, J ) 12.3, 4.7 Hz, 0.6H), 4.20 (dd, J ) 12.3, 4.8 Hz, 0.4H),
4.09 (dd, J ) 12.3, 2.4 Hz, 0.4H), 4.08 (dd, J ) 12.4, 2.4 Hz,
0.6H), 4.06-3.98 (m, 1H), 2.61-2.53 (m, 1H), 2.24-1.90 (m,
14H), 1.48 (s, 1.8H), 1.46 (s, 1.2H); 13C NMR (100 MHz, CDCl3,
major isomer) δ 170.5, 169.8, 169.6, 168.6, 108.6, 94.2, 94.0, 70.2,
69.5, 65.7, 62.1, 37.3, 31.5, 23.7, 20.9, 20.7, 20.6, 20.5; HRFABMS
calcd for C18H26O12Na (M + Na)+ 457.1322, found 457.1317.
2-Aceton yl-1,3,4,6-tetr a -O-a cetyl-2-d eoxy-R-D-m a n n op y-
r a n ose (14).24 To a solution of ozonide 13 (59 mg, 0.14 mmol)
in anhydrous CH2Cl2 (3 mL) at rt were added zinc dust (95 mg,
1.4 mmol) and acetic acid (0.20 mL). The reaction mixture was
allowed to stir for 30 min and filtered. After the filtrate was
concentrated, toluene was added and the solution was concen-
trated in vacuo. The resulting residue was purified by flash
column chromatography (50% EtOAc/hexanes) to give compound
14 as a clear syrup (51 mg, 94%): [R]24 +51.7 (c 1.20, CHCl3);
D
both 1H and 13C NMR data were identical to the reported
values.24
Ack n ow led gm en t. Financial support from the NIH
(DK 54759) and the Cystic Fibrosis Foundation is
gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: General experimen-
1
tal conditions and the H and 13C NMR spectra for compound
13. This material is available free of charge via the Internet
at http://pubs.acs.org.
J O020362K
7564 J . Org. Chem., Vol. 67, No. 21, 2002