Preparation of Aldehydo Sugars and Sugar Acids via Ozonolysis of Sugar Hydrazones

Full text of DOI:10.1021/jo970067d

J . Org. Chem. 1997, 62, 4507-4509
4507
Sch em e 1
P r ep a r a tion of Ald eh yd o Su ga r s a n d Su ga r
Acid s via Ozon olysis of Su ga r Hyd r a zon es
Roxanne P. Spencer, Hye Kyung Bae Yu,
Cullen L. Cavallaro, and J effrey Schwartz*
Department of Chemistry, Princeton University,
Princeton, New J ersey 08544-1009
Received J anuary 13, 1997X
For a recent investigation into carbon chain shortening
methodology, we required ready access to variously
substituted gluconic acids. However, although aldehydo
sugars are important intermediates in natural product
synthesis,1 no methodology existed for the preparation
of acyclic sugar acids which were appropriately protected
to avoid spontaneous lactonization. The common ap-
proach to acyclic carbohydrate derivatives, ring-opening
via the dithioacetals,2 was incompatible with protecting
groups required for our subsequent investigations, and
attempts to prepare the acid through hydrolysis of
protected gluconolactones were unsuccessful. We now
report that selectively protected gluconic acids can be
prepared from cyclic sugars via formation of an acyclic
hydrazone. It is interesting that, while sugar hydrazones
have long been used as derivatives to characterize
sugars,3,4 they have not been well examined heretofore
as synthetic intermediates in their own right.
Hydrazones are readily formed by heating a lactol with
a hydrazine in alcohol.5-7 The acyclic hydrazone (1a ; 1H
NMR for H1, ca. δ 7) and a cyclic hydrazine isomer (1b;
1H NMR for H1, ca. δ 4)8,9 exist in facile equilibrium
(Scheme 1) which is solvent dependent. Only the cyclic
hydrazine isomer 1b was observed in chloroform; in
pyridine, H1 was recorded as a sharp signal at δ 6.3,
suggesting that 1a and 1b were in fast equilibrium with
1a the dominant species. Methylation of the C-5 hy-
droxyl of 1a gave 2. Ozonolytic reactivity of hydrazone
CdN double bonds is known to be N-substituent-depend-
ent in simple cases.10 In preliminary work, C-5 OH
groups of sugar (2,5-dichlorophenyl)hydrazones 1a and
4 were protected by reaction with methyl iodide, which
resulted, as well, in N-methylation. The N-(2,5-dichlo-
rophenyl)-N-methylhydrazone of glucose (2) or of 2-de-
oxyribose (5) readily underwent ozonolysis9,10 to give
aldehydes 3 and 6, respectively (Scheme 1).
4-Deoxy compound 1112 was prepared from commer-
cially available methyl 4,6-O-benzylideneglucopyranoside
10 in straightforward fashion (Scheme 2). Benzylation13
followed by reductive ring opening of the benzylidene
acetal gave methyl 2,3,6-tri-O-benzylglucopyranoside15 in
good yield. Reduction of the 4-O-triflate by NaBH415 and
acidic hydrolysis of the methyl glycoside gave 11.12
However, extending the hydrazone ozonolysis methodol-
ogy described above to include more labile silyl ether
protecting groups at C-5 OH was only moderately suc-
cessful. In particular, silylation of (2,5-dichlorophenyl)-
hydrazone 7 gave O-silylated 8; no N-silylation was
noted, and ozonolysis gave aldehydo sugar 9 in only 36%
yield (see Scheme 1). To test the hypothesis that N,N-
disubstitution might abet ozonolysis, 13 was prepared
from 11 by reaction with ethanolic 1,1-dimethylhydrazine
followed by silylation with TBDMS triflate in pyridine.
X Abstract published in Advance ACS Abstracts, J une 1, 1997.
(1) For representative examples of acyclic sugar aldehydes in
synthesis, see (a) Lichtenthaler, F. W.; Lorenz, K.; Ma, W.-Y. Tetra-
hedron Lett. 1987, 28, 47-50. (b) Marco-Contelles, J .; Pozuelo, C.;
J imeno, M. L.; Mart´ınez, L.; Mart´ınez-Grao, A. J . Org. Chem. 1992,
57, 2625-2631. (c) Burgess, K.; Chaplin, D. A.; Henderson, I.; Pan, Y.
T.; Elbein, A. D. J . Org. Chem. 1992, 57, 1103-1109. (d) Tadano, K.;
Maeda, H.; Hoshino, M.; Iimura, Y.; Suami, T. J . Org. Chem. 1987,
52, 1946-1956. (e) Roush, W. R.; Michaelides, M. R.; Tai, D. F.; Lesur,
B. M.; Chong, W. K. M.; Harris, D. J . J . Am. Chem. Soc. 1989, 111,
2984-2995. (f) Hezczegh, P.; Kova´cs, I.; Szila´gyi, L.; Varga, T.; Dinya,
Z.; Sztarieskai, F. Tetrahedron Lett. 1993, 34, 1121-1214.
(2) Wander, J . D.; Horton, D. Adv. Carbohydr. Chem. Biochem. 1976,
32, 15-123.
(3) Simon, H.; Kraus, A. In Synthetic Methods for Carbohydrates;
El Khadem, H. S., Ed.; American Chemical Society: Washington, D.
C., 1976, pp 188-206.
(4) Mester, L.; El Khadem, H. S. In The Carbohydrates: Chemistry
and Biochemistry; 2nd ed.; Pigman, W., Horton, D., Eds.; Academic
Press: New York, 1980; Vol. 1B, pp 929-988.
(5) Stroh, H.-H.; Scharnow, H.-G. Chem. Ber. 1965, 98, 1588-1597.
(6) Newkome, G. R.; Fishel, D. L. J . Org. Chem. 1966, 31, 677-
681.
(7) For preparation of aldose hydrazones, see (a) Wright, J . A. In
Methods in Carbohydrate Chemistry; Whistler, R. L., BeMiller, J . N.,
Eds.; Academic: New York, 1972; Vol. VI; pp 201-205. (b) Williams,
J . M. Carbohydr. Res. 1983, 117, 89-94. (c) Tipson, R. S. In Nucleic
Acid Chemistry; Townsend, L. B., Tipson, R. S., Eds.; Wiley & Sons:
New York, 1986; Vol. 3, pp 33-34. (d) Koo´s, M.; Mosher, H. S. Collect.
Czech. Chem. Commun. 1985, 50, 1994-1999. (e) Blair, H. S.; Roberts,
G. A. F. J . Chem. Soc. (C) 1967, 2425-2427.
(10) Lassaletta, J .-M.; Ferna´ndez, R. Tetrahedron Lett. 1992, 33,
3691-3694.
(11) Enders, D.; Kipphardt, H.; Fey, P. Org. Synth. 1987, 65, 183-
189.
(12) Kihlberg, J .; Frejd, T.; J ansson, K.; Kitzing, S.; Magnusson, G.
Carbohydr. Res. 1989, 185, 171-190.
(13) Barrett, A. G. M.; Read, R. W.; Barton, D. H. R. J . Chem. Soc.,
Perkin Trans. 1 1980, 2184-2190.
(8) (a) Collins, P.; Ferrier, R. Monosaccharides: Their Chemistry and
Their Roles in Natural Products; Wiley & Sons: Chichester, 1995. (b)
Somogyi, L. Carbohydr. Res. 1978, 64, 289-292.
(14) (a) Garegg, P. J .; Hultberg, H. Carbohydr. Res. 1981, 93, C10-
C11. (b) Garegg, P. J .; Hultberg, H.; Wallin, S. Carbohydr. Res. 1982,
108, 97-101.
(9) Szilagyi, L.; Gyorgydeak, Z.; Duddeck, H. Carbohydr. Res. 1986,
158, 67-79.
(15) Barrette, E.-P.; Goodman, L. J . Org. Chem. 1984, 49, 176-178.
S0022-3263(97)00067-4 CCC: $14.00 © 1997 American Chemical Society

4508 J . Org. Chem., Vol. 62, No. 13, 1997
Notes
Sch em e 2
then give the protected gluconic acids; both the sugar
aldehydes and acids can be of importance for the further
synthesis of elaborated glycoside species.25
Exp er im en ta l Section
Materials were obtained from Aldrich Chemical Company and
used without further purification. Ozone was generated using
a Wellsbach Model T-408 Lab Ozonizer (100 V, 6.2 psi of O2,
flow rate ) 1.5 L/min) and was bubbled through the solutions
of the hydrazones until they were pale blue in color.
2,3-Di-O-ben zylglu cose (2,5-Dich lor op h en yl)h yd r a zon e
(1). A solution of 2.44 g (6.78 mmol) 2,3-di-O-benzylglucose
(prepared by benzylation of 10 followed by hydrolysis) and (2,5-
dichlorophenyl)hydrazine (1.44 g, 8.14 mmol) in 200 mL of
methanol was refluxed for 18 h. Workup and chromatography
gave 3.54 g (quant yield) of product. 1H NMR (CD3CN): δ 7.44-
7.27 (m, 11 H), 7.20 (d, J ) 8.6 1 H), 6.70 (dd, J ) 2.6, 8.6, 1 H),
6.45 (br s, 1 H), 4.92 (d, J ) 10.9, 1 H), 4.86 (d, J ) 11.2, 1 H),
4.81 (d, J ) 11.2, 1 H), 4.73 (d, J ) 10.9, 1 H), 4.66 (d, J ) 10.2,
1 H), 4.09 (dd, J ) 8.9, 10.2, 1 H), 3.75 (ddd, J ) 3.0, 6.9, 11.9,
1 H), 3.52 (dt, J ) 5.9, 11.8, 1 H), 3.46-3.38 (m, 3 H), 3.30 (t, J
) 8.9, 1 H), 3.23 (ddd, J ) 2.6, 5.9, 8.9, 1 H), 2.89 (dd, J ) 2.6,
11.8, 1 H); 13C (CD3COCD3): δ 147.1, 140.2, 139.6, 130.8, 128.9,
128.7, 128.6, 128.2, 128.1, 127.8, 118.8, 116.2, 114.4, 91.3, 86.6,
80.7, 78.1, 75.5, 75.4, 71.9; IR (KBr) 1596 cm-1 (CdN). Anal.
Calcd for C26H28Cl2N2O5: C, H, N.
2,3-Di-O-ben zyl-4,5,6-tr i-O-m eth ylglu cose N-(2,5-Dich lo-
r op h en yl)-N-m eth ylh yd r a zon e (2). To a KOH slurry (3.0 g;
53.6 mmol KOH in 20 mL of DMSO) were added 1 (2.23 g, 4.28
mmol) and methyl iodide (2.0 mL, 4.6 g, 32.4 mmol), and the
resulting mixture was stirred overnight at room temperature.
Workup and chromatography gave 2.42 g (98%) of the title
compound. 1H NMR (CD3COCD3): δ 7.44-7.15 (m, 13 H), 7.03
(d, J )6.9, 1 H), 4.85 (d, J ) 10.9, 1 H), 4.73 (d, J ) 12.2, 1 H),
4.62 (d, J ) 10.9, 1 H), 4.57 (d, J ) 12.1, 1 H), 4.44 (t, J ) 6.9,
1 H), 3.94 (dd, J ) 3.6, 6.9, 1 H), 3.71 (dd, J ) 2.6,10.6, 1 H),
3.65 (dd, J ) 3.6, 6.6, 1 H), 3.50 (ddd, J ) 2.6, 4.6, 6.6, 1 H),
3.43 (dd, J ) 4.6, 10.6, 1 H), 3.41 (s, 3 H), 3.33 (s, 3 H), 3.29 (s,
3 H), 3.22 (s, 3 H); 13C (CD3CN): δ 148.8, 140.0, 139.7, 138.0,
133.5, 129.3, 129.2, 129.0, 128.9, 128.5, 128.4, 126.6, 126.5, 126.3,
81.0, 80.9, 80.4, 75.1, 71.8, 71.1, 60.3, 59.1, 57.6, 39.8; IR (neat)
1605 cm-1 (CdN). For C30H36Cl2N2O5, HRMS, 574.2001 (cal-
culated), 574.1992 (measured).
2,3-Di-O-ben zyl-4,5,6-tr i-O-m eth yl-a ldeh ydo-D-glu cose (3).
A solution of 411 mg (0.71 mmol) of 2 in ethyl acetate was cooled
to -78 °C, and ozone was then bubbled through this solution (1
h). Dimethyl sulfide was added, and the mixture was concen-
trated. Chromatography (50% ether in hexanes) gave 3 (246
mg, 86%). 1H NMR (CD3COCD3): δ 9.22 (s, 1 H), 7.45-7.25
(m, 10 H), 4.88 (d, J ) 11.8, 1 H), 4.79 (d, J ) 11.2, 1 H), 4.62
(d, J ) 11.2, 1 H), 4.56 (d, J ) 11.8, 1 H), 4.25 (d, J ) 5.9, 1 H),
4.15 (dd, J ) 2.6, 5.9, 1 H), 3.73 (dd, J ) 1.6,10.2, 1 H), 3.54
(dd, J ) 2.6, 7.6, 1 H), 3.47 (m, 1 H), 3.42 (dd, J ) 3.6, 10.2, 1
H), 3.31 (s, 3 H), 3.28 (s, 3 H), 3.18 (s, 3 H); 13C (CD3CN): δ
200.7, 139.3, 139.2, 129.4, 129.2, 128.9, 128.8, 81.3, 80.8, 80.0,
79.1, 74.2, 73.7, 70.4, 59.9, 59.0, 57.4; IR (neat) 1729 cm-1 (CdO).
For C23H30O6, HRMS, 402.2042 (calculated), 402.1964 (mea-
sured).
Indeed, ozonolysis gave 9 in high yield (94%); qualita-
tively, ozonolysis of 13 proceeded about five times faster
than that of 2 or 5.16
Oxidation of 9 to gluconic acid 14 required conditions
that would tolerate the acid sensitive silyl ether protect-
ing group. Initial attempts using Cr(VI) or permanga-
nate reagents gave the desired carboxylic acid, but yields
were variable, and tedious purification steps were re-
quired. Sodium chlorite oxidation17,18 has been reported
to tolerate a broad range of functionality and is compat-
ible with carbohydrate substrates.19,20 Indeed, 14 could
be prepared (98%) simply by chlorite oxidation of 9 in
buffered media. Debenzylation of the acid required a
modified transfer hydrogenolysis procedure;21,22 incom-
plete debenzylation was often noted under normal hy-
drogenolysis conditions.
The approach described herein for the synthesis of
acyclic aldehydo sugars complements that for the prepa-
ration of sugar oximes.23 While traditional preparations
of acyclic sugars via dithioacetals involve reaction with
alkanethiols in HCl,2 hydrazones can be prepared under
mild conditions. And, because hydrazones can be syn-
thesized from variously protected aldoses,24 ozonolysis of
the hydrazone is an efficient route to a broad range of
acyclic sugar aldehydes. Subsequent mild oxidation can
2-Deoxyr ibose (2,5-Dich lor op h en yl)h yd r a zon e (4).
A
mixture of 2-deoxyribose (4.91 g, 36.6 mmol) and (2,5-dichlo-
rophenyl)hydrazine (9.00 g, 50.8 mmol) in 100 mL of methanol
was heated to reflux overnight. Workup and chromatography
gave 4 (10.63 g, 99%) as product. 1H NMR (CD3COCD3): δ 8.80
(br s, 1 H), 7.64 (t, J ) 5.6, 1 H), 7.43 (d, J ) 2.6, 1 H), 7.25 (d,
J ) 8.2, 1 H), 6.73 (dd, J ) 2.6, 8.2 1 H), 3.98-3.52 (m, 7 H),
2.71 (ddd, J ) 3.6, 5.6, 14.9, 1 H), 2.48 (ddd, J ) 5.9, 8.6, 14.9,
1 H); 13C (CD3COCD3): δ 146.6, 132.7, 130.3, 117.7, 114.8, 112.9,
(16) Enhanced rates for dioxirane oxidation of alkyl vs aryl hydra-
zones have been noted. See, Altamura, A.; Curci, R.; Edwards, J . O. J .
Org. Chem. 1993, 58, 7289-7293.
(17) (a) Kraus, G. A.; Roth, B. J . Org. Chem. 1980, 45, 4825-4830.
(b) Kraus, G. A.; Taschner, M. J . J . Org. Chem. 1980, 45, 1175-1176.
(18) Lindgren, B. O.; Nilsson, T. Acta Chem. Scand. 1973, 27, 888-
890.
(19) Bal, B. S.; W. E. Childers, J .; Pinnick, H. W. Tetrahedron 1981,
37, 2091-2096.
(25) For preparation of disaccharides by cyclization of carbohydrate-
derived side chains, see, (a) Haneda, T.; Goekjian, P. G.; Kim, S. H.;
Kishi, Y. J . Org. Chem. 1992, 57, 490-498. (b) Wang, Y.; Babirad, S.
A.; Kishi, Y. J . Org. Chem. 1992, 57, 468-481. (c) Goekjian, P. G.;
Wu, T.-C.; Kang, H.-Y.; Kishi, Y. J . Org. Chem. 1991, 56, 6422-6434.
(d) Martin, O. R.; Lai, W. J . Org. Chem. 1990, 55, 5188-5190. (e)
Carcano, M.; Nicotra, F.; Panza, L.; Russo, G. J . Chem. Soc., Chem.
Commun. 1989, 642-643. (f) Lay, L.; Nicotra, F.; Pangrazio, C.; Panza,
L.; Russo, G. J . Chem. Soc., Perkin Trans. 1 1994, 333-338.
(20) Mio, S.; Kumagawa, Y.; Sugai, S. Tetrahedron 1991, 47, 2133-
2144.
(21) Hanessian, S.; Liak, T. J .; Vanasse, B. Synthesis 1981, 396-
397.
(22) Petit, J .-M.; Sinay¨, P. Carbohydr. Res. 1978, 64, 9-16.
(23) Weitz, D. J .; Bednarski, M. D. J . Org. Chem. 1989, 54, 4957-
4959.
(24) Bae Yu, H. K. Ph.D. Thesis, Princeton University, 1992.

Notes
J . Org. Chem., Vol. 62, No. 13, 1997 4509
86.6, 67.8, 66.9, 66.8, 32.7; IR (KBr) 1597 cm-1 (CdN). Anal.
Calcd for C11H24Cl2N2O3: C, H, N.
(d, J ) 11.2, 1 H), 4.57 (d, J ) 11.87 Hz, 1 H), 4.53 (d, J ) 10.9,
1 H), 4.48 (s, 2 H), 4.40 (d, J ) 11.86, 1 H), 4.02 (dd, J ) 5.93,
6.92 1 H), 3.94-3.83 (m, 2 H), 3.40 (dd, J ) 4.45, 9.6, 1 H), 3.33
(dd, J ) 6.59, 9.6, 1 H), 2.93 (d, J ) 4.94, 1 H) 2.74 (s, 6 H),
1.62-1.52 (m, 2 H); 13C (CD3COCD3) δ 139.3, 139.1, 138.9, 133.6,
83.0, 82.2, 77.5. 73.1, 67.5, 66.2, 42.5, 42.3, 35.6; IR (neat): 1498
cm-1 (CdN). Anal. Calcd for C29H36O4N2: C, H, N. HRMS:
476.2674 (calculated); 476.2691 (measured).
2,3,6-Tr i-O-ben zyl-4-d eoxy-5-O-ter t-bu tyld im eth ylsilyl-
D-xylo-h exose N,N-Dim eth ylh yd r a zon e (13). A solution of
860 mg (1.8 mmol) of 12 in 20 mL of anhydrous pyridine was
stirred under N2 overnight with 0.5 mL (2.2 mmol, 1.2 equiv) of
TBDMSOTf. The mixture was poured into CHCl3, washed first
with 1 M HCl and then with water, and dried (MgSO4).
Concentration and chromatography (10% EtOAc in hexanes)
gave 13 (930 mg; 88%) as a thick, yellow syrup. 1H NMR
(CDCl3): δ 7.2-7.4 (m, 15 H), 6.38 (d, J ) 7.25 Hz, H1), 4.81 (d,
J ) 11.21, 1 H), 4.61 (d, J ) 11.88 Hz, 1 H), 4.52 (d, J ) 11.22,
1 H), 4.48 (d, J ) 11.88, 1 H), 4.47 (s, 2 H), 4.07 (dd, J ) 6.2,
7.26 H2), 4.06 (t, J ) 6, H5), 3.88 (q, J ) 6.2, H3), 3.36 (d, J )
4.75, 2 × H6), 2.78 (s, 6 H), 1.72-1.78 (m, 2 × H4), 0.88 (s, 3 H),
0.87 (s, 3 H), 0.83 (s, 3 H), 0.034 (s, 3 H), 0.020 (s, 3 H); IR
(neat): 1471 cm-1 (CdN). For C35H50O4NSi, HRMS: 590.3539
(calculated); 590.3528 (measured).
2,3,6-Tr i-O-ben zyl-4-d eoxy-5-O-(ter t-bu tyld im eth ylsilyl)-
D-xylo-h exon ic Acid (14). A solution of 140 mg (0.26 mmol)
of 9 in 5 mL of tert-butyl alcohol and 2 mL of water was stirred
with 60 mg (0.50 mmol, 2 equiv) of NaH2PO4 and 0.1 mL of
2-methyl-1-butene (0.93 mmol, 3.5 equiv) for 5 min. To this, 70
mg (0.77 mmol, 3 equiv) of NaOCl2 was added, and the mixture
was stirred for 3 h. The reaction was quenched by addition of
3 mL of saturated Na2SO3 solution, and the reaction mixture
was poured into 1 M HCl and extracted with CH2Cl2. The
combined organic layers were washed (water and brine) and
dried (Na2SO4). Concentration gave 14 (140 mg; 97%) as a pale
yellow syrup. 1H NMR: (C6D6): δ 7.0-7.32 (m, 15 H), 4.75 (d,
J ) 11.3 Hz, 1 H), 4.61 (d, J ) 11.6 Hz, 1 H), 4.59 (d, J ) 11.3
Hz, 1 H), 4.33 (dd, J ) 4.1, 9.2 Hz, 1 H), 4.20 (s, 2 H), 4.17 (d,
J ) 11.7 Hz, 1 H), 4.10 (d, J ) 4.2 Hz, 1 H), 3.10-3.29 (m, 3 H),
2.07 (ddd, J ) 14, 9.2, 3.3, 1 H), 1.97 (ddd, J ) 14, 9.2, 3.3, 1
H),).956 (s, 9 H), 0.081 (s, 3 H), 0.060 (s, 3 H); 13C (CDCl3): δ
174.28, 138.17, 137.89, 136.91, 128.35, 128.09, 127.98, 127.95,
127.868, 127.68, 75.05, 73.21, 72.96, 72.48, 36.16; IR (neat): 1725
cm-1 (CdO). Anal. Calcd for C33H44O6Si, C, H.
2-Deoxy-3,4,5-tr i-O-m eth yl-D-er yth r o-p en tose N-(2,5-d i-
ch lor op h en yl)-N-m eth ylh yd r a zon e (5). The title compound
was prepared as for 2 (88%). 1H NMR (CD3COCD3): δ 7.42 (d,
J ) 8.2, 1 H), 7.33 (d, J ) 2.6, 1 H), 7.13 (dd, J ) 2.6, 8.2, 1 H),
7.10 (t, J ) 4.9, 1 H), 3.59-3.51 (m, 2 H), 3.47-3.40 (m, 2 H),
3.41 (s, 3 H), 3.38 (s, 3 H), 3.31 (s, 3 H), 3.12 (s, 3 H), 2.64-2.49
(m, 2 H); 13C (CD3CN): δ 149.7, 138.9, 133.4, 132.3, 126.1,
125.84, 125.81, 82.1, 80.1, 72.6, 59.1, 58.6, 58.2, 39.8, 34.5; IR
(neat) 1582 cm-1 (CdN). For C15H22Cl2N2O3: HRMS, 348.1007
(calculated), 348.1014 (measured).
2-Deoxy-3,4,5-tr i-O-m eth yl-a ld eh yd o-D-er yth r o-p en tose
(6). Ozonolysis as for 3 gave 6 (83%). 1H NMR (CDCl3): δ 9.75
(t, J ) 2.3, 1 H), 3.83 (dt, J ) 5.6, 6.3, 1 H), 3.51 (dd, J ) 4.3,
10.5, 1 H), 3.44 (dd, J ) 4.3, 10.5, 1 H), 3.35 (dt, J ) 4.3, 5.6, 1
H), 3.41 (s, 3 H), 3.39 (s, 3 H), 3.35 (s, 3 H), 2.69 (ddd, J ) 2.3,
5.6, 16.5, 1 H), 2.60 (ddd, J ) 2.3, 5.6, 16.5, 1 H); 13C (CD3CN):
δ 202.1, 81.9, 77.4, 72.3, 59.2, 58.7, 58.0, 45.6; IR (neat) 1724
cm-1 (CdO). For C8H16O4: HRMS, (M - 1) 175.0970 (calcu-
lated), 175.0962 (measured).
2,3,6-Tr i-O-b en zyl-4-d eoxy-D-xylo-h exose (2,5-Dich lo-
r op h en yl)h yd r a zon e (7). The title compound was prepared
as for 1. 1H NMR (pyridine-d5): δ 7.86 (d, J ) 2.6, 1 H), 7.67
(d, J ) 8.2, 1 H), 7.55-7.22 (m, 15 H), 6.74 (dd, J ) 2.6, 8.2, 1
H), 6.24 (d, J ) 9.2, 1 H), 5.17 (d, J ) 10.6, 1 H), 5.03 (d, J )
10.6, 1 H), 4.96 (s, 2 H), 4.77 (d, J ) 11.9, 1 H), 4.71 (d, J )
11.9, 1 H), 4.38 (t, J ) 8.9, 1 H), 3.87-3.57 (m, 4 H), 2.23 (ddd,
J ) 1.3, 4.9, 12.2, 1 H), 1.65 (m, 1 H).
2,3,6-Tr i-O-ben zyl-4-d eoxy-5-O-(ter t-bu tyld im eth ylsilyl)-
D-xylo-h exose (2,5-Dich lor op h en yl)h yd r a zon e (8). The title
compound was prepared as for 13. 1H NMR (CDCl3) δ 7.81 (s,
1 H), 7.47 (d, J ) 1.8, 1 H), 7.4-7.2 (m, 15 H), 7.18 (d, 8.3, 1 H),
7.04 (d, J ) 7.2, 1 H), 6.77 (dd, J ) 1.8, 8.2, 1 H), 4.74 (d, J )
11.4, 1 H), 4.68 (d, J ) 12, 1 H), 4.58 (d, J ) 11.5, 1 H), 4.55 (d,
J ) 12, 1 H), 4.49 (s, 2 H), 4.23 (dd, J ) 5.8, 6.8, 1 H), 4.0-4.13
(m, 1 H), 3.96-3.91 (m, 1 H), 3.39 (d, J ) 4.6, 2 H), 1.84-1.78
(2 H), 0.91 (s, 9 H), 0.07 (s, 2 H), 0.05 (s, 3 H); 13C NMR
(CDCl3): δ 141.55, 139.14, 138.88, 138.68, 134.54, 130.54, 130.40,
129.98, 128.82, 128.76, 128.56, 128.18, 127.92 120.36, 115.46,
114.65, 90.43, 77.73, 75.87, 73.84, 73.15, 71.77, 69.46, 36.86, 1.71,
-2.26, -2.90, -3.02, -3.18, -4.03
2,3,6-Tr i-O-ben zyl-4-d eoxy-5-O-(ter t-bu tyld im eth ylsilyl)-
a ld eh yd o-D-xylo-h exose (9). From (dichlorophenyl)hydrazone
8: Ozonolysis as for 3 gave 9 (36%). From dimethylhydrazone
13: Ozonolysis of 13 (384 mg, 0.64 mmol) for 10 min gave 9
(333 mg; 94%) as a clear, colorless syrup. The aldehyde slowly
oxidizes in air to give 2,3,6-tri-O-benzyl-4-deoxygluconic acid
(14). 1H NMR: (CDCl3): δ 9.78 (d, J ) 1.4, 1 H). 7.2-7.4 (m,
15 H), 4.75 (d, J ) 11.8 Hz, 1 H), 4.61 (d, J ) 4.0 Hz, 2 H), 4.60
(d, J ) 11.8 Hz, 1 H), 4.44 (s, 2 H), 4.06-4.16 (m, 2 H), 3.96 (dd,
J ) 1.4, 4.3, 1 H) 3.42 (dd, J ) 5.5, 9.7, 1 H), 3.38 (dd, J ) 5.2,
9.7, 1 H), 1.88 (dd, J ) 4.2, 7.6 Hz, 2 H), 0.932 (s, 3 H), 0.895 (s,
3 H), 0.992 (s, 3 H), 0.060 (s, 3 H), 0.051 (s, 3 H); 13C (C6D6): δ
201.7, 138.4, 138.3, 137.6, 126.0, 125.97, 125.7, 125.6, 125.3, 76.2,
75.2, 72.9, 72.8, 72.6, 72.0, 68.8, 36.3, -4.0, -4.2, -4.9, -5.0,
-5.1; IR (neat); 1732 (C)O). For C33H44O5Si: MS (FAB): cal-
culated: m/z 548 (100.00), 549 (42.97), 550 (13.26), 551 (2.89);
found: 548 (100), 549 (42), 550 (13), 551 (2).
2,3,6-Tr i-O-b en zyl-4-d eoxy-D-xylo-h exose N,N-Dim et h -
ylh yd r a zon e (12). A solution of 880 mg (2.03 mmol) of 11 in
15 mL of ethanol was heated to reflux with 10 mg of p-
toluenesulfonic acid monohydrate and 0.25 mL (3.29 mmol, 1.6
equiv) of N,N-dimethylhydrazine for 3 h. The solution was
cooled, concentrated, and chromatographed (1:1 Et2O/hexanes)
to give 12 (678 mg; 70%) as a clear, colorless syrup. 1H NMR
(CD3CN): δ 7.2-7.4 (m, 15 H), 6.43 (d, J ) 7.2 Hz, 1 H), 4.72
4-Deoxy-5-O-(ter t-bu tyldim eth ylsilyl)-D-xylo-h exon ic Acid
(15). A solution of 225 mg (0.40 mmol) of 14 in 10 mL of EtOH
was stirred with 60 mg of 10% Pd on carbon and 500 µL of
cyclohexene under H2 for 5 days to give 15 (90 mg; 76%) as a
clear colorless oil. 1H NMR (D2O): δ 4.05 (m, 1 H), 3.94 (m, 1
H), 3.80 (d, J ) 2.58, 1 H), 3.53 (d, J ) 5, 2 H), 1.70 (ddd, J )
3.1, 10.8, 14, 1 H), 1.56 (ddd, J ) 1.8, 9, 14, 1 H), 0.82 (s, 9 H),
0.01 (s, 6 H); IR (neat): 1715 cm-1 (CdO).
Ack n ow led gm en t. The authors thank the National
Institutes of Health and the National Science Founda-
tion for support of this research.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra for
compounds 2, 3, 5-9, 13, and 15. Complete elemental analysis
data for compounds 1, 4, 12, and 14 (11 pages). This material
is contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
J O970067D