Synthesis of 3-deoxy-α-D-manno-oct-2-ulosonic acid glycoside (Kdo) and its 2-deoxy analogue: A Horner-Emmons approach

Article abstract of DOI:10.1021/ol990931j

(formula presented) A very simple and potentially valuable synthetic approach to 3-deoxy-α-D-manno-oct-2-ulosonic acid glycoside is described. The key reaction in the synthesis is the construction of ketene dithioacetal from the corresponding 2-deoxy-D-ma

Full text of DOI:10.1021/ol990931j

ORGANIC
LETTERS
1999
Vol. 1, No. 11
1709-1711
Synthesis of
3-Deoxy-r-D-manno-oct-2-ulosonic Acid
Glycoside (Kdo) and Its 2-Deoxy
Analogue: A Horner−Emmons
Approach†
Jacek Młynarski and Anna Banaszek*
Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Warsaw, Poland
mlynar@ichf.edu.pl
Received August 11, 1999
ABSTRACT
A very simple and potentially valuable synthetic approach to 3-deoxy-r-D-manno-oct-2-ulosonic acid glycoside is described. The key reaction
in the synthesis is the construction of ketene dithioacetal from the corresponding 2-deoxy-D-manno-heptono-1,5-lactone and 1,3-dithianyl
anion. The synthesis ends with a tandem oxidative hydrolysis of the dithianyl group/glycosylation process.
3-Deoxy-R-D-manno-oct-2-ulosonic acid glycoside (Kdo) is
a component of all lipopolysaccharides (LPS) of Gram-
negative bacteria playing a central role in their growth.1 It
occours also in many acidic exopolysaccharides (K-antigens)
located at the cell surface of the bacteria2 as well as in cell
walls of plants.3 Therefore, Kdo has generated considerable
interest in its synthesis,1,4 and it is still a current topic of
research investigations.5
During the course of our synthetic studies toward ulosonic
acids6 we have reported on a unique stereocontrolled
approach to the isomeric 3-deoxy-hept-2-ulosonic acids based
on the reaction of sugar lactones with the 1,3-dithianyl anion
(l) Haudrechy, A.; Sinay¨, P. Tetrahedron Lett. 1990, 31, 5765. (m) Frick,
W.; Kru¨lle, T.; Schmidt, R. R. Liebigs Ann. Chem. 1991, 435. (n) Giese.
B.; Carboni, B.; Go¨bel, T.; Muhn, R.; Wetterich, F. Tetrahedron Lett. 1992,
33, 2673. (o) Houdrechy, A.; Sinay¨, P. J. Org. Chem. 1992, 57, 4142. (p)
Giese, B.; Linker, T. Synthesis 1992, 46. (q) Sugai, T.; Shen, G.-J.; Ichikawa,
Y.; Wong, Ch.-H. J. Am. Chem. Soc. 1993, 115, 5, 413. (r) Lubineau, A.;
Auge´, J.; Lubin, N.; Tetrahedron 1993, 49, 4639. (s) Coutrot, Ph.; Grison,
C.; Tabyaoui, M. Tetrahedron Lett. 1993, 34, 5089. (t) Dondoni, A.; Marra,
A.; Merino, P.; J. Am. Chem. Soc. 1994, 116, 3324. (u) Sato, K.; Miyata,
T.; Tanai, I.; Yonezawa, Y. Chem. Lett. 1994, 129. (v) Gao, J.; Ha¨rter, R.;
Gordon, D. M.; Whitesides, G. M. J. Org. Chem. 1994, 59, 3714. (w) Lo´pez-
Herrera, F. J.; Sarabia-Garcia, F.; Tetrahedron Lett. 1994, 35, 6705. (x)
Craig, D.; Pennington, M. W.; Warner, P. Tetrahedron Lett. 1995, 36, 5815.
(5) (a) Coutrot, P.; Grison, C.; Lecouvey, M. Tetrahedron Lett. 1996,
37, 1595. (b) Barton, D. H. R.; Jaszberenyi, J. C.; Liu, W.; Shinada, T.
Tetrahedron 1996, 52, 2717. (c) Du, S.; Plat, D.; Baasov, T. Tetrahedron
Lett. 1996, 37, 3545. (d) Tsukamoto, H.; Takahashi, T. Tetrahedron Lett.
1997, 38, 6415. (e) Pakulski, Z.; Zamojski, A. Tetrahedron 1997, 53, 3723.
(f) Bra¨uer, N.; Kirsching, A.; Schaumann, E. Eur. J. Org. Chem. 1998,
2729. (g) Schlessinger, R. H.; Pettus, L. H.; J. Org. Chem. 1998, 63, 9089.
(h) Hu, Y.-J.; Huang, X.-D.; Yao, Z.-J.; Wu, Y.-L. J. Org. Chem. 1998,
63, 2456. (i) Jiang, S.; Rycroft, A. D.; Singh, G.; Wang, X.-Z.; Wu, Y.-L.
Tetrahedron Lett. 1998, 39, 3809. (j) Burke, S. D.; Sametz, G. M. Org.
Lett. 1999, 1, 71.
† This work was presented at the 10th European Carbohydrate Sympo-
sium, Galway, July 11-16, 1999, Abstract PA069.
(1) Unger, F. M. AdV. Carbohydr. Chem. Biochem. 1981, 38, 323 and
references therein cited.
(2) Holst, O.; Brade, H. In Bacterial Endotoxic Lipopolysaccharides;
Morrison, D. C., Ryan, J. L., Eds.; CRC Press: Boca Raton, FL, 1992;
Vol. 1, p 135.
(3) York, W. S.; Darvill, A. G.; McNeil, M.; Albersheim, P. Carbohydr.
Res. 1985, 138, 109.
(4) (a) Danishefsky, S. J.; Pearson, W.H.; Segmuller, B. E. J. Am. Chem.
Soc. 1985, 107, 1280. (b) Imoto, M.; Kasumoto, S.; Shiba, T. Tetrahedron
Lett. 1987, 28, 6235. (c) Ramage, R.; Rose, G. W. Tetrahedron Lett. 1988,
29, 4877. (d) Bednarski, M. D.; Crans, D. C.; DiCosimo, R.; Simon, E. S.;
Stein, P. D.; Whitesides, G. M. Tetrahedron Lett. 1988, 29, 427. (e)
Branchaud, B. P.; Meier, M. S. Tetrahedron Lett. 1988, 29, 3191. (f) Itoh,
H.; Kaneko, T.; Tanami, K.; Yoda, K. Bull. Chem. Soc. Jpn. 1988, 61,
3356. (g) Harito, S.; Amano, M.; Hashimoto, H. J. Carbohydr. Chem. 1989,
8, 681. (h) van der Klein, P. A. M.; Boons, G. J. P. H.; Veeneman, G. A.;
van der Marel, G. A.; van Boom, J. H. Tetrahedron Lett. 1989, 30, 5477.
(i) Martin, S. F.; Zinke, P. W. J. Am. Chem. Soc. 1989, 111, 2311. (j)
Branchaud, B. P.; Meier, M. S. J. Org. Chem. 1989, 54, 1320. (k) Dondoni,
A.; Fantin, G.; Fogagnolo, M.; Merino, P. Tetrahedron Lett. 1990, 31, 4513.
(6) (a) Banaszek, A. Tetrahedron 1995, 51, 4231. (b) Młynarski, J.;
Banaszek, A. Carbohydr. Res. 1996, 295, 69. (c) Młynarski, J.; Banaszek,
A. Tetrahedron 1997, 53, 10643.
10.1021/ol990931j CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/02/1999

was succeeded by the standard reaction with 9-BBN to give
the alcohol 3.11 Attempted direct conversion of 3 into 4 was
unsuccessful. Therefore, 3 was first acetylated and then 5-OH
was regioselectively deprotected using a TES-TFA mix-
ture.12 Subsequent hydrolysis of the acetyl residue furnished
the diol 4.13 Finally, 4 was cyclized to the lactone 5 in nearly
quantitative yield, employing PCC as a reagent.14
Scheme 1a
The elaboration of the O-benzyl-protected lactone 5 into
the required Kdo 7 is shown in Scheme 2. Formation of the
Scheme 2a
a (a) Me2PhSiCH2MgCl, THF, 90 °C; (b) KH, THF, 60 °C, then
BnBr, rt; (c) 9-BBN, THF, then, H2O2 30%, NaOHaq; (d) Ac2O,
Py; (e) TES, TFA, CH2Cl2, rt; (f) K2CO3, MeOH, rt; (g) PCC,
dichloroethane, 60 °C.
to create ketene thioacetals as key intermediates.7 In this
Letter, we describe our synthetic design for the glycoside of
3-deoxy-R-D-manno-oct-2-ulosonic acid (Kdo) and its 2-deoxy
analogue. A major problem for this synthesis is the efficient
construction of the O-benzyl-protected 2-deoxy-D-manno-
heptono-1,5-lactone moiety. The known 3,4:6,7-di-O-iso-
propylidene derivative4o was not suitable for the reaction with
the 1,3-dithianyl anion due to its steric rigidity.7
a (h) KHMDS, THF, -78 °C/rt; (i) NBS, MeOH, CH2Cl2, rt; (j)
Pd-C, H2, EtOH; (k) LiBH4, TMSCl, THF, 50 °C; (l) NBS, THFaq,
rt, then CH2N2, Et2O.
Scheme 1 illustrates the synthesis of the required lactone
5 from the mannose 18 using for the elongation reaction a
protocol similar to that developed by Nicotra et al.9 Modify-
ing their procedure we applied Me2PhSiCH2MgCl as the
most convenient Grignard reagent. Addition of this reagent
to 1 gave the intermediate silyl derivative as a mixture of
two separable isomers. These, without separation, underwent
an elimination reaction with KH to afford the sole product.
Its sequential benzylation provided the terminal olefin 2.10
The stage was now set for a terminal hydroxylation. This
ketene dithioacetal 6 was best achieved using a Horner-
Emmons reaction, with 2-[bis(2,2,2-trifluoroethoxy)phos-
phoryl]-1,3-dithiane15 as a reagent.
Presumably, the strong electron-withdrawing character of
the trifluoroethoxy substituent enhances the elimination step
of the Horner-Emmons reaction, thus avoiding a compara-
tive elimination process in the carbohydrate ring.7 To
generate the dithianyl anion, potassium bis(trimethylsilyl)-
amide was used, according to the previously described
procedure.7 Addition of 5 at -78 °C (1.0 mmol scale), then
(7) (a) Młynarski, J.; Banaszek, A. Tetrahedron Lett. 1998, 39, 5425.
(b) Młynarski, J.; Banaszek, A. Tetrahedron 1999, 55, 2785.
(8) Vasella, A.; Witzig, Ch.; Waldraff, Ch.; Uhlmann, P.; Briner, K.;
Bernet, B.; Panza, L.; Husi, R. HelV. Chim. Acta 1993, 76, 2847.
(9) Lay, L.; Nicotra, F.; Panza, L.; Gusso, G.; Sello, G. J. Carbohydr.
Chem. 1998, 17, 1269.
chromatography (hexane-ether, 5:1) afforded 2 (1.75 g, 62%) as a colorless
1
syrup: [R]D -30.3 (c 1.08); H NMR (200 MHz, CDCl3) δ 3.64 (t, 1H, J
) 10.3 Hz), 3.90 (m, 1H), 4.10-4.50 (m, 4H), 4.50-4.80 (3 × ABq, 3 ×
2H, CH2Ph), 5.24-5.56 (m, 2H, H-1a, H-1b), 5.35 (s, 1H, benzylidene),
5.80-6.06 (m, 1H, H-2), 7.15-7.50 (m, 20H, Ar); HR-MS (LSIMS) calcd
for C35H36O5 [M + Na]+ 559.2460, found 559.2476.
(10) To a stirred suspension of magnesium (390 mg, 16.05 mmol) with
a few crystals of sublimate in dry tetrahydrofuran (25 mL) was added
dropwise (chloromethyl)dimethylphenylsilane (2.96 mL, 16.05 mmol) under
reflux. After the Grignard reagent formation was complete (the appearance
of the dark-graphite color of the mixture), a solution of mannose 1 (2.4 g,
5.35 mmol) in dry THF was added and the mixture was refluxed for 3-4
h. The reaction mixture was diluted with ethyl ether and quenched with a
saturated aqueous solution of NH4Cl and brine. After drying and evaporation
of the solvents, column chromatography (hexane-ether, 1:1) gave an
intermediate silyl derivative (two separable isomers; HR-MS (LSIMS) calcd
for C36H42O6Si [M + Na]+ 621.2648 found 621.2654). Both addition
products (∼2 g) were dissolved in dry THF (20 mL) and treated with an
excess of potassium hydride (∼13.4 mmol suspension in mineral oil) at 0
°C. The solution was stirred for 1 h at 50 °C (TLC). The reaction mixture
was then recooled to 0 °C, and benzyl bromide (0.83 mL, 7 mmol) was
added dropwise. After 1 h at room temperature the mixture was diluted
with ethyl ether, and methanol was cautiously added, followed by washing
with brine. Evaporation of solvents left a syrup which after column
(11) To a solution of 2 (1.7 g, 3.17 mmol) in dry THF (20 mL) was
added dropwise 9-BBN (20 mL, ∼0.5 M solution in THF, 9.5 mmol) at
room temperature. The mixture was stirred for 5 h at room temperature
and then diluted with tetrahydrofuran (30 mL); 30% H2O2 was then added
(30 mL) at 0 °C, followed by aqueous NaOH 4% (30 mL). The reaction
mixture was warmed to room temperature and stirred for 1 h, then diluted
with CHCl3, washed with water, and dried. Removal of the solvents under
reduced pressure and chromatography of the residue (hexane-ether, 1:1)
afforded 3 (1.0 g, 57%) as a colorless syrup: [R]D -11.5 (c 1.60); 1H NMR
(200 MHz, CDCl3) δ 1.85-2.15 (m, 2H, H-2a, H-2b), 3.64 (t, 1H, J ) 9.9
Hz), 3.75 (m, 1H), 3.82-4.10 (m, 6H), 4.42-4.85 (3 × ABq, 3 × 2H,
CH2Ph), 5.42 (s, 1H, benzylidene), 7.20-7.50 (m, 20H, Ar). Anal. Calcd
for C35H38O6 [554.68]: C, 75.79; H, 6.91. Found: C, 75.69; H, 6.90.
(12) DeNinno, M. P.; Etienne, J. B.; Duplantier, K. C. Tetrahedron Lett.
1995, 36, 669.
1710
Org. Lett., Vol. 1, No. 11, 1999

mainting the reaction mixture at room temperature for about
3 h afforded, after usual workup ketene dithioacetal 6 in 71%
yield.16
A tandem oxidative hydrolysis of the dithianyl group/
glycosylation reaction by NBS-MeOH in CH2Cl2 provided
the glycoside of the Kdo derivative 7 in 91% yield, with
full stereoselectivity.17 The benzyl residues were readily
removed by hydrogenolysis to give 8.18 The NMR spectra
of O-acetyl derivative 919 were similar to those reported by
Unger.20
Conversion of 6 to the 2-deoxy-Kdo derivative 10 required
three operations: (i) reduction of the olefinic linkage in 6
(LiBH4-TMSCl), (ii) oxidative hydrolysis of the 1,3-
dithianyl residue (NBS-THF-H2O), (iii) esterification of
the resulting carboxyl function (CH2N2 in Et2O). The
2-deoxy-Kdo derivative 1021 was isolated as the sole product.
Its structure was confirmed by NMR data comparable to
those of an analogous benzyl derivative of 2-deoxy-D-lyxo-
heptulosonic acid methyl ester.7
In summary, we have succeeded in the preparation of a
fully protected O-benzyl 2-deoxy-D-manno-heptono-1,5-
lactone, utilized in the unique two-step synthesis of the
methyl glycoside of Kdo. This approach may have value for
the synthesis of disaccharides and other more complex
glycosides by analogy to the preparation of R-glycosides/
disaccharides of 3-deoxy-D-lyxo-hept-2-ulosonic acid.22
(13) Compound 3 (1.5 g, 2.70 mmol) was acetylated in the usual way at
room temperature with an Ac2O-Py system. After evaporation of the
reagents with toluene, the resulting acetate was dissolved in CH2Cl2 (10
mL). Triethylsilane (2.0 mL, 12.55 mmol) and then trifluoroacetic acid (0.86
mL, 11.3 mmol) were added dropwise at 0 °C. The temperature was allowed
to rise to room temperature during 1 h, with stirring (TLC). The mixture
was diluted with ethyl ether and washed with NaHCO3 and water. The
solvents were evaporated, and the residue was filtered through a short
column of silica gel. The crude product dissolved in methanol (10 mL)
was stirred with an excess of K2CO3 at room temperature for 30 min. The
reaction mixture was filtered through Celite and then through a column of
silica gel to give 4 (780 mg, 52%): mp 49 °C; [R]D -20.3 (c 0.62); 1H
NMR (200 MHz, CDCl3) δ 1.90-2.10 (m, 3H, H-2a, H-2b, OH), 3.12 (d,
1H, J ) 5.9 Hz, OH), 3.60-3.98 (m, 8H), 4.32-4.79 (4 × ABq, 4 × 2H,
CH2Ph), 7.20-7.50 (m, 20H, Ar); HR-MS (LSIMS) calcd for C35H40O6
[M + Na]+ 579.2723, found 579.2743.
Acknowledgment. This work was supported by a re-
search grant from KBN (3TO 9A 09312).
OL990931J
(14) A mixture of PCC (700 mg, 3.24 mmol) and heptitol 5 (450 mg,
0.81 mmol) was stirred in 1,2-dichloroethane (20 mL) at 60 °C for 1 h and
then poured onto a column of silica gel prepared in hexane. Elution with
hexane-ether (3:2) gave lactone 5 in almost quantitative yield (440 mg)
as an oil: [R]D -4.2 (c 1.09); 1H NMR (500 MHz, CDCl3) δ 2.90 (dd, 1H,
J ) 7.17, 17.8 Hz, H-2eq), 2.96 (dd, 1H, J ) 10.8, 17.7 Hz, H-2ax), 3.70
(dd, 1H, J ) 3.5, 10.8 Hz, H-7a), 3.85 (dd 1H, J ) 2.01, 10.9 Hz, H-7b),
3.89-3.94 (m, 2H, H-3, H-6), 4.36 (dd, 1H, J ) 1.5, 9.3 Hz, H-5), 4.39
(bs, 1H, H-4), 4.35-5.07 (4 × ABq, 4 × 2H, CH2Ph), 7.23-7.36 (m, 20H,
Ar); 13C NMR (CDCl3) δ 33.1, 67.4, 70.3, 70.8, 71.8, 73.5, 74.0, 74.8,
75.5, 76.3, 127.3-128.6 and 137.3-138.3 (Ar), 169.0; HR-MS (LSIMS)
calcd for C35H36O6 [M + Na]+ 575.2410, found 575.2455.
(18) After hydrogenolysis of 7 with H2 on Pd-C catalyst in an EtOH
solution, 8 was obtained as an oil: 1H NMR (500 MHz, D2O) δ 1.98 (dd,
1H, J ) 11.3, 12.9 Hz, H-3ax), 2.12 (ddd, 1H, J ) 0.8, 5.1, 12.9 Hz, H-3eq),
3.28 (s, 3H, OMe), 3.71 (dd, 1H, J ) 1.0, 9.0 Hz, H-6), 3.73 (dd, 1H, J )
6.1, 11.8 Hz, H-8a), 3.92 (s, 3H, CO2Me), 3.97 (dd, 1H, J ) 2.9, 11.8 Hz,
H-8b), 4.02 (ddd, 1H, J ) 3.2, 6.1, 9.0 Hz, H-7), 4.12 (m, 1H, H-5), 4.14
(ddd, 1H, J ) 2.9, 5.1, 11.6 Hz, H-4); 13C NMR (D2O) δ 33.4, 51.1, 53.4,
62.8, 65.3, 65.7, 68.9, 71.6, 99.3, 170.3.
(19) Acetylation of 8 with acetic anhydride and pyridine gave 9: [R]D
1
(15) Mikołajczyk, M.; Graczyk, P. P.; Wieczorek, M. W. J. Org. Chem.
1994, 59, 1672.
+65.7 (c 1.04); (lit.20 +76.8, c 0.62); H NMR (500 MHz, C6D6) δ 1.63,
1.67, 1.75, 1.80 (4s, 4 × 3H, 4Ac), 2.25 (dd, 1H, J ) 11.9, 12.6 Hz, H-3ax),
2.30 (ddd, 1H, J ) 0.8, 5.4, 12.6 Hz, H-3eq), 3.10 (s, 3H, OMe), 3.27 (s,
3H, CO2Me), 3.90 (dd, 1H, J )1.4, 9.8 Hz, H-6), 4.16 (dd, 1H, J ) 4.9,
12.2 Hz, H-8a), 4.66 (dd, 1H, J )2.4, 12.2 Hz, H-8b), 5.51 (ddd, 1H, J )
2.4, 4.8, 9.8 Hz, H-7), 5.56 (ddd, 1H, J ) 3.0, 5.4, 11.9 Hz, H-4), 5.62 (m,
1H, H-5); 13C NMR (C6D6) δ 20.1, 20.2, 20.3, 20.3, 32.5, 51.1, 51.9, 62.6,
64.7, 66.7, 67.9, 69.1, 99.6, 167.4, 169.3, 169.4, 169.7, 170.2.
(16) A solution of potassium bis(trimethylsilyl)amide (1.8 mL, 0.90 mmol
∼0.5 M solution in toluene) was added dropwise to 2-[bis(2,2,2-trifluoro-
ethoxy)phosphoryl]-1,3-dithiane (330 mg, 0.9 mmol) dissolved in anhydrous
THF (5 mL) at -78 °C under Ar. The temperature was maintained at -78
°C for 1 h, and then a solution of 5 (250 mg, 0.45 mmol) in THF (1-2
mL) was added dropwise. The reaction was stirred for ∼3 h while the
temperature was allowed to rise to room temperature. The reaction was
neutralized with TFA, and the crude product was purified by flash
chromatography (hexane-ether, 4:1) to give 215 mg of 6 (72%): [R]D
+61.4 (c 0.70); 1H NMR (500 MHz, CDCl3) δ 2.12-2.17 (m, 2H, H-2′ax,
H-2′eq), 2.63 (dd, 1H, J ) 11.0, 13.9 Hz, H-3ax), 2.75-2.90 (m, 4H, H-1′ax,
H-1′eq, H-3′ax, H-3′eq), 3.37 (ddd, 1H, J ) 0.8, 5.0, 14.0 Hz, H-3eq),
3.69 (ddd, 1H, J ) 2.1, 5.0, 11.9 Hz, H-4), 3.74 (d 1H, J ) 9.5 Hz, H-6),
3.84 (dd, 1H, J ) 4.2, 10.7 Hz, H-8a), 4.00-4.05 (m, 2H, H-7, H-8b),
4.27 (bs, 1H, H-5), 4.41-5.11 (4×ABq, 4 × 2H, CH2Ph), 7.25-7.40 (m,
20H, Ar); 13C NMR (CDCl3) δ 25.58, 27.9, 29.6, 30.2, 69.1, 70.4, 72.0,
72.1, 73.5, 74.0, 76, 0, 76.7, 77.5, 77.7, 127.3-128.4 and 138.1-139.0
(Ar), 150.3; HR-MS (LSIMS) calcd for C39H42O5S2 [M]+ 654.2474, found
654.2490.
(17) A solution of 6 (160 mg, 0.24 mmol) in CH2Cl2 (2 mL) was treated
with methanol (0.5 mL) and NBS (88 mg, 0.50 mmol). The mixture was
stirred at room temperature for ∼0.5 h and then filtered through a short
column of silica gel and evaporated. The residue was purified by
chromatography (hexane-ether, 4:1) on silica to give the desired ester 7
as a colorless oil (140 mg, 91%): [R]D +12.8 (c 1.00); 1H NMR (500 MHz,
CDCl3) δ 2.23-2.27 (m, 2H, H-3ax, H-3eq), 3.18 (s, 3H, OMe), 3.74 (dd,
1H, J ) 3.4, 10.7 Hz), 3.77 (s, 3H, CO2Me), 3.83-3-87 (m, 2H), 3.96-
4.02 (m, 2H), 4.16 (bs, 1H, H-5), 4.33-5.04 (4 × ABq, 4 × 2H, CH2Ph),
7.21-7.34 (m, 20H, Ar); 13C NMR (CDCl3) δ 32.9, 50.9, 52.4, 67.7, 70.5,
71.0, 71.7, 72.1, 73.3, 74.0, 75.5, 75.9, 99.3, 127.2-128.3 and 138.2-
139.2 (Ar), 168.6; HR-MS (LSIMS) calcd for C38H42O8 [M + Na]+
649.2777, found 649.2778.
(20) Unger, F. M.; Stix, D.; Schulz, G. Carbohydr. Res. 1980, 80, 191.
(21) To a mixture of LiBH4 (11 mg, 0.5 mmol) in dry THF (2 mL) was
added TMSCl (160 µL, 1.25 mmol) at room temperature under Ar, and the
reaction was stirred for 1 h at room temperature. Then a solution of ketene
dithioacetal 7 (65 mg, 0.1 mmol) in THF (2 mL) was added dropwise. The
mixture was slowly warmed to 40-50 °C (TLC). Then methanol was
cautiously added, followed by neutralization with saturated aqueous
NaHCO3. The aqueous layer was extracted with ether. After concentration,
the crude product was redissolved in a mixture of THF-water (9:1, 3 mL)
and NBS (178 mg, 1 mmol) was added in one portion at room temperature.
The mixture was stirred until TLC showed disappearance of the substrate.
The reaction was washed with saturated aqueous Na2SO3 and extracted with
AcOEt. The organic layers were washed with brine, dried, and concentrated.
The resulting crystals were redissolved in ether (with an excess of AcOEt)
and treated with a solution of CH2N2 in ether. After evaporation, the residue
was chromatographed on silica gel to give the desired 2-deoxy ester 10
(60%): [R]D +3.6 (c 0.80); 1H NMR (500 MHz, C6D6) δ 2.10 (m, 1H,
H-3eq), 2.40 (dd, 1H, J ) 12.6 Hz, H-3ax), 3.24 (ddd, 1H, J ) 2.5, 4.4,
11.8 Hz, H-4), 3.32 (s, 3H, CO2Me), 3.55 (dd, 1H, J ) 1.0, 9.0 Hz, H-6),
3.73 (dd, 1H, J ) 2.4, 12.1 Hz, H-2), 3.86 (m, 2H, H-8a, H-8b), 4.14 (dt,
1H, J ) 2.9, 6.0, 8.9 Hz, H-7), 4.17 (m, 1H, H-5), 4.19-5.20 (4 × ABq,
4 × 2H, CH2Ph), 7.05-7.24 (m, 20H, Ar); 13C NMR (C6D6) δ 29.8, 51.3,
69.2, 70.2, 72.0, 73.0, 73.5, 74.7, 75.3, 77.5, 79.1, 96.4, 127.3-128.5 and
139.4-139.9 (Ar), 170.2; HR-MS (LSIMS) calcd for C37H40O7 [M]+
619.2672, found 619.2680.
(22) Młynarski, J.; Banaszek, A. Pol. J. Chem. 1999, 73, 973.
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