Regioselective acylation of secondary hydroxyl groups by means BOP-Cl

Article abstract of DOI:10.1081/SCC-200036630

Methyl 2-O-acyl α-D-glucopyranosides are regioselectively formed with good yields by acylation of the correspondent 6-O-trityl pyranosides with carboxylic acids and (BOP-Cl). No acyl migration was observed in the deblocking of the primary hydroxyl group w

Full text of DOI:10.1081/SCC-200036630

SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 22, pp. 4207–4217, 2004
Regioselective Acylation of Secondary
Hydroxyl Groups by Means BOP-Cl
Renato Dalpozzo, Antonio De Nino, Loredana Maiuolo,
*
Antonio Procopio, Giovanni Sindona, and Antonio Tagarelli
`
Dipartimento di Chimica, Universita della Calabria,
Arcavacata di Rende (CS), Italy
ABSTRACT
Methyl 2-O-acyl a-D-glucopyranosides are regioselectively formed with
good yields by acylation of the correspondent 6-O-trityl pyranosides with
carboxylic acids and (BOP-Cl). No acyl migration was observed in the
deblocking of the primary hydroxyl group with p-toluensulfonic acid.
Key Words: BOP-Cl; Sugar; Methyl a-D-glucopyranoside; Secondary
hydroxyl group.
Selective monoacylation of one of the many hydroxyl groups in monosac-
charides is an important step in many synthetic procedures. Partially esterified
*
`
Correspondence: Antonio Procopio, Dipartimento di Chimica, Universita della
Calabria, Ponte Bucci, I-87030 Arcavacata di Rende (CS), Italy; Fax: þ39 984
492055; E-mail: procopio@unical.it.
4207
DOI: 10.1081/SCC-200036630
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

4208
Dalpozzo et al.
carbohydrates find applications in both scientific and technological research
areas. They are widely used in food chemistry[1] and cosmetics[2] and are valu-
able intermediates in sugar chemistry.[3] They are important surfactants for
biological studies[4] and unique tools for drug delivery processes across cellu-
lar membranes.[5] The higher reactivity of primary vs. secondary hydroxyl
groups of carbohydrates has been exploited in the selective acylation[6–8] or
phosphorylation.[9]
A regioselective formation of a number of 6-O- and 50-O esters of methyl
a,D-glucopyranosides and nucleosides, respectively, has been already
achieved with a variety of carboxylic acids, aminoacids, and peptides[10–13]
by means of bis (2-oxo-3-oxazolidinyl) phosphinic chloride (BOP-Cl, 1,
Scheme 1).[14] The regiochemistry of the process has been related to the reac-
tivity of the intermediate mixed anhydride (3a–e) formed between BOP-Cl
and the acid derivative (2a–e), and to steric constrains experienced by the
approaching nucleophilic sites of the sugar substrates.
Here the effectiveness of BOP-Cl is exploited in the selective protection
of the secondary hydroxyl groups of 6-O-tritylated glucopyranosides by
means of commercially available carboxylic acids. The trityl group (Tr)
was chosen for the transient protection of the 6-OH group of methyl
a-D-glucopyranoside. This synthetic strategy was aimed at obtaining a
clean removal of the temporary protection without interfering with the anome-
ric acetal linkage. Acid deblocking of the 6-OTr function could catalyze the
thermodynamically controlled acyl migration within the secondary hydroxyl
groups, but this risk is negligible for glucopyranosides if appropriate exper-
imental conditions are chosen.[15] Tritylation of methyl a-D-glucopyranoside
with trityl chloride in pyridine at 708C, in the presence of dimethylamino pyr-
idine (DMAP) afforded the correspondent 6-O-trityl derivative 4 in good
yield.[16] It is interesting to note that the classical tritylation procedure[17] is
Scheme 1.

Regioselective Acylation of Secondary Hydroxyl
4209
unsuitable for the protection of the gluco derivative; in fact, low yields (36%)
were obtained when it was tritylated in pyridine at room temperature, whereas
at 1008C a mixture of compounds was formed. The structure of 4 was
1
easily assigned by H-NMR spectroscopy and fast-atom bombardment mass
spectrometry (FAB-MS).
The effectiveness of BOP-Cl as activating agent of carboxylic acids in the
regioselective esterification of secondary hydroxyl groups in 6-O-protected
monosaccharides was studied with the partially protected monosaccharide 4.
Although the reactions of carboxylic acids (2a–e) in the presence of BOP-
Cl (1)/DMAP in pyridine are based on a preliminary activation of the acyl
group through the formation of the mixed anhydrides 3a–e[14] (Scheme 1),
the subsequent formation of reactive symmetrical carboxylic anhydrides and
acyl pyridinium derivatives cannot be excluded.
The reaction of 4 with BOP-Cl and benzoic acid 2a affords mainly methyl
6-O-trityl-2-O-benzoyl a-D-glucopyranoside (5a), and 6a and 7a as side
products (Scheme 2).
The data reported in Table 1 show that product yield is little affected
by the ratios of substrate, reagents, and acylating agent used. Therefore,
the experimental conditions reported in row 1 represent a useful compro-
mise because a smaller excess of BOP-Cl and acid are required. The
2-O-benzoyl derivative 5a (Scheme 2) was obtained after workup and short
column chromatography. Structural assignment has been performed by
1H-NMR spectroscopy, by means of extensive decoupling experiments.
In particular, the H-2 proton of 5a showed a low field signal with respect to
the unprotected derivative 4, and it was easily identified from the correlation
with H-1 and H-3 protons. The structures of 6a and 7a were assigned similarly.
FAB-MS provided the appropriate (M-H)2 and fragment ions. When the
Scheme 2.

4210
Dalpozzo et al.
Table 1. Benzoylation of methyl 6-O-trityl a-D-glucopyranoside 4 with BOP-Cl in
different experimental conditions.
Reagent rel. ratio
Yield %
Time
(hr)
4
2a
DMAP
BOP-Cl
5a
6a
7a
1.0
1.0
1.0
1.0
1.2
1.5
2.5
3.0
1.2
1.5
2.5
3.0
2.4
3.0
3.7
4.5
15
24
2
72.6
67.1
76.7
71.7
2.5
3.4
4.2
4.5
13.8
11.9
12.7
12.3
1
acylation process was carried out with benzoyl chloride in pyridine using
the same ratio of acylating agent as for the BOP-Cl-mediated process, a
mixture of the same compounds was obtained with lower regioselectivity.
The reactivity order experienced in the above reported reaction is in agree-
ment with earlier findings[18] (i.e., the equatorial 2-OH is the more reactive
secondary group). The regioselective acylation of the secondary hydroxyl
groups of a glucopyranoside can be achieved, therefore, directly from car-
boxylic acids by chemical methods with relative yields similar to those
reported for the analogous enzymatic processes.[19]
Insights into the acylation mechanism of the BOP-Cl-mediated process
have been achieved by carrying out the same esterification with substituted
benzoic (2b–d) and 1-naphthyl acetyl (2e) acids. A lower regioselectivity
was experienced when p-nitrobenzoic acid 2b was used (Table 2). The elec-
tronic effect of the p-nitro group presumably increases the reactivity of the
activated carboxylic group lowering the selectivity of the acylating process.
It has been observed that the reactivity of the mixed anhydrides 3
(Scheme 1) is also lightly controlled by the bulkiness of the acyl moiety.[11]
The acylation reaction with 2-nitrobenzoic acid 2c (Table 2) was slower
Table 2. Acylation of methyl 6-O-trityl-a-D-glucopyranoside(4) with BOP-Cl.
Yield (%)
Carboxylic
acids
Time
(hr)
m.p.
(8C)
Entry
5(a–e)
6(a–e)
7(a–e)
1
2
3
4
5
2a
2b
2c
2d
2e
15
1
85–86
86–87
65–66
78–79
82–83
72.6
65.5
56.2
70.3
72.5
2.5
6.3
13.8
28.0
14.2
9.3
7
19.6
20.3
16.2
2
16
11.2

Regioselective Acylation of Secondary Hydroxyl
4211
than the corresponding esterification with the 4-nitro isomer showing that this
effect is particularly important when the target is a secondary sugar hydroxyl
group.
The 2-chlorobenzoic acid (2d) behaves as expected on the basis of the
results so far reported, whereas the 2,6-dichloro derivative did not react
with the same substrate even after prolonging the reaction time. It is
known that the 2,6-dichlorobenzoic acid/BOP-Cl system is effective in the
regioselective protection of the primary hydroxyl sugar moieties of gluco
and mannopyranosides.[10] The lower reactivity observed with secondary
hydroxyl groups has, therefore, to be ascribed to the steric hindrance of
the sugar secondary hydroxyl groups. Accordingly, no reaction was obtained
when 4 was treated with 2,6-dichlorobenzoyl chloride in pyridine in a clas-
sical acylating procedure. The comparison of entries 3 and 5 (Table 2)
allows the discrimination between steric and electronic effects. Both 2c
and 2e activated in situ by BOP-Cl undergo esterification with similar total
conversion, after considerably different reaction times. On the basis of the
experimental data, it can be suggested that the observed different regioselecti-
vity is directly related to the bulkiness of the nucleophile and inversely pro-
portional to the electrophilicity of the activated carboxyl group. Apart from
the effect that a bulky 6-O trityl group may exert on the selective acylation of
the secondary hydroxyl groups of pyranosides, the inversion of configuration
of one of the ring carbon atoms affects at a greater extent the relative nucleo-
philicity of the linked hydroxyl groups. Among the number of procedures
available for the detritylation process,[20] the best results were obtained
when an excess of p-toluenesulfonic acid in dichloromethane was used at
room temperature. The methyl 2-O-acyl-a-D-glucopyranosides 8a–e were
obtained with satisfactory isolated yields in only 15 min. No concomitant
acyl migration or hydrolysis of the glycosidic linkage were observed.
The data reported above clearly show that conventional chemistry can be
successfully used for the selective acylation of methyl a-D-glucopyranoside
at the C-2 through the transient protection of the primary hydroxyl group
with the trityl group.
EXPERIMENTAL
Bis (2-oxo-3-oxazolidinyl) phosphinic chloride (BOP-Cl) was prepared
as previously reported.[14] Methyl a-D-glucopyranoside and carboxylic
acids (2a–e) were purchased from Fluka or Aldrich and were used without
further purification. Pyridine was distilled from calcium hydride and stored
under nitrogen. Dimethylformamide was distilled from phosphorus pentoxide
and stored over Type 3A activated molecular sieves. Silica gel-precoated

4212
Dalpozzo et al.
plates were used for TLC, and Kieselgel 60 H without gypsum was used for
short-column chromatography. NMR spectra were obtained from WM-300
Bruker spectrometer with Me4Si as internal standard and CDCl3 or
DMSO-d6 as solvents. Decoupling experiments allowed the measurement
of the coupling constants in the case of multiplet signals; J values are
given in Hz. FAB-Mass spectra were obtained on a Micromass (VG) ZAB
2F mass spectrometer, from 2 mm3 of glycerol solution of sample by the stan-
dard gun operated with a neutral Xenon beam of 8 KeV and a neutral current
of 10 mA. Melting points have been determined by a Kofler hot stage and are
uncorrected.
Methyl 6-O-trityl-a-D-glucopyranoside (4)
A literature method[19] was followed with some modifications. A solution
of a-D-glucopyranoside (5.049 g, 0.026 mol), trityl chloride (8.085 g,
0.029 mol), triethylamine (TEA) dry (6.25 mL), and dimethylaminopyridine
DMAP (0.159 g, 0.0013 mol) in dry pyridine (120 mL) was stirred at 708C
for 12 hr, until a nearly complete conversion of substrate was achieved
[TLC, CHCl3-MeOH (90 : 10 v/v)]. The organic solution was washed with
saturated aq. NH4Cl and then with water. The dried organic layers afforded,
after solvent evaporation to dryness, a yellowish oily residue which after
recrystallization from ethanol gave 4.
m.p. 153–1548C (lit[17] 154–1558C), 70% yield. 1H-NMR (DMSO)
d (ppm): 7.49–7.18 (15 H, m, Ar), 4.92–4.75 (2H, m, 3-OH, 4-OH), 4.68
(1H, d, H1; J1,2 ¼ 3.62), 4.42–4.23 (1H, m, 2-OH), 3.68–3.59 (1H, m, H6a),
3.47 (1H, m, H3; J3,4 ¼ 9.41), 3.42 (3H, s, OCH3) 3.42–3.25 (2H, m, H2,
H4), 3.15–3.03 (2H, m, H5, H6b, J5,6b ¼ 9.63). FABMS (-) m/z 435
(42.2%, M-H)2, 193 (100).
Synthesis of Derivatives 5a–e
General procedure. A mixture of 4 (1.0 mmol), of appropriate carboxylic
acid 2a–e (1.2 mmol), BOP-Cl (2.4 mmol), and DMAP (1.2 mmol) in dry
pyridine (25 mL) was allowed to react at room temperature. The progress
of the reaction was followed by TLC [TLC, CHCl3-MeOH (95 : 5 v/v)]
(Table 2). Saturated aq. NaHCO3 was then added, and the mixture was
extracted with CH2Cl2. The organic layers were washed with saturated aq.
NH4Cl and water and evaporated to dryness, which gave yellowish oily resi-
dues that were purified by short-column chromatography [CHCl3-MeOH
(97.5 : 2.5 v/v)] to give 5a–e (Table 2).

Regioselective Acylation of Secondary Hydroxyl
4213
Methyl 2-O-benzoyl-6-O-trityl-a-D-glucopyranoside (5a)
1H-NMR (CDCl3) d (ppm): 8.15–7.21 (20H, m, Ar), 5.05 (1H, d, H-1;
J1,2 ¼ 3.65), 4.95 (1 H, dd, H-2; J2,3 ¼ 9.97), 4.10 (1H, dd, H-3;
J3,4 ¼ 8.65), 3.85–3.71 (1H, m, H-5; J5,6 ¼ 4.90), 3.65 (1H, dd, H-4;
J4,5 ¼ 9.65), 3.62–3.41 (2H, m, H-6; Jgem ¼ 9.22), 3.38 (3H, s, CH3). Anal.
calcd. for C33H32O7: C 73.32; H 5.97. Found C 73.20; H 6.00.
Methyl 2-O-4-nitrobenzoyl-6-O-trityl-a-D-glucopyranoside (5b)
1H-NMR (CDCl3) d (ppm): 8.20–7.10 (19H, m, Ar), 5.05 (1H, d, H-1;
J1,2 ¼ 3.16), 4.95 (1H, dd, H-2; J2,3 ¼ 9.90), 4.09 (1H, dd, H-3;
J3,4 ¼ 8.90), 3.75–3.64 (1H, m, H-5; J5,6 ¼ 5.00), 3.61 (1H, dd, H-4;
J4,5 ¼ 9.53), 3.59–3.40 (2H, m, H-6; Jgem ¼ 9.18), 3.38 (3H, s, CH3). Anal.
calcd. for C33H31NO9: C 67.68; H 5.33; N 2.39. Found C 67.80; H 5.30; N
2.40.
Methyl 2-O-2-nitrobenzoyl-6-O-trityl-a-D-glucopyranoside (5c)
1H-NMR (CDCl3) d (ppm): 7.92–7.24 (19 H, m, Ar), 5.05 (1 H, d, H-1;
J1,2 ¼ 3.64), 4.98 (1H, dd, H-2; J2,3 ¼ 9.83), 3.99 (1H, dd, H-3; J3,4 ¼ 9.21),
3.73–3.65 (1H, m, H-5; J5,6 ¼ 4.86), 3.62 (1H, dd, H-4; J4,5 ¼ 9.67),
3.59–3.42 (2H, m, H-6; Jgem ¼ 9.41), 3.40 (3 H, s, CH3). Anal. calcd. for
C33H31NO9: C 67.68; H 5.33; N 2.39. Found C 67.70; H 5.35; N 2.40.
Methyl 2-O-o-chlorobenzoyl-6-O-trityl-a-D-glucopyranoside (5d)
1H-NMR (CDCl3) d (ppm): 8.00–7.15 (19H, m, Ar), 5.09 (1H, d, H-1;
J1,2 ¼ 3.58), 4.91 (1H, dd, H-2; J2,3 ¼ 8.52), 4.05 (1H, dd, H-3;
J3,4 ¼ 9.58), 3.83–3.71 (1H, m, H-5; J5,6 ¼ 5.00), 3.65 (1H, dd, H-4;
J4,5 ¼ 9.78), 3.62–3.40 (2H, m, H-6; Jgem ¼ 9.21), 3.39 (3H, s, CH3). Anal.
calcd. for C33H31ClO7: C 69.93; H 5.43; Cl 6.16. Found C 70.00; H 5.45;
Cl 6.15.
Methyl 2-O-1-naphthyl acetyl-6-O-trityl-a-D-
glucopyranoside (5e)
1H-NMR (CDCl3) d (ppm): 8.00–7.12 (22 H, m, Ar), 4.89 (1H, d, H-1;
J1,2 ¼ 3.62), 4.68 (1H, dd, H-2; J2,3 ¼ 9.80), 3.90 (1H, dd, H-3;

4214
Dalpozzo et al.
J3,4 ¼ 9.04), 3.77–3.61 (1H, m, H-5; J5,6 ¼ 4.79), 3.51 (1H, dd, H-4;
J4,5 ¼ 9.77), 3.49–3.32 (2H, m, H-6; Jgem ¼ 9.56), 3.30 (3H, s, CH3). Anal.
calcd. for C38H36O7: C 78.48; H 6.00. Found C 78.60; H 5.90. Synthesis of
8a–e. General procedure. A solution of 5a–e (0.5 mmol) and p-toluensulfonic
acid (1.5 mmol) in CH2Cl2 (10 cm3) was stirred for 15–25 min. The oily resi-
dues obtained, after solvent evaporation, were purified by short-column
chromatography [CHCl3-MeOH (95 : 5 v/v)] to give 8a–e.
Methyl 2-O-benzoyl-a-D-glucopyranoside (8a)
m.p. 125–1278C, 68% yield. 1H-NMR (DMSO) d (ppm): 8.50–7.50 (5 H,
m, Ar), 5.30 (1H, d, OH, J ¼ 5.76), 5.20 (1H, d, OH, J ¼ 5.76), 4.87 (1H, d,
H-1; J1,2 ¼ 3.49), 4.67 (1H, dd, H-2; J2,3 ¼ 9.80), 4.60 (1H, t, OH, J ¼ 5.80),
3.76 (1H, ddd, H-3; J3,4 ¼ 9.57), 3.68 (1H, ddd, H-4; J4,5 ¼ 9.20), 3.61–3.48
(1H, m, H-5; J5,6 ¼ 5.85), 3.46–3.33 (2H, m, H-6; Jgem ¼ 14.01), 3.35 (3H, s,
CH3). Anal. calcd. for C14H18O7: C 56.37; H 6.08. Found C 56.50; H 6.05.
FABMS (-) m/z 297 (100%, M-H)2, 193 (22.8).
Methyl 4-O-p-nitrobenzoyl-a-D-glucopyranoside (8b)
m.p. 110–1128C, 77% yield. 1H-NMR (DMSO) d (ppm): 8.42–7.10 (4H,
m, Ar), 5.43 (1H, d, OH, J ¼ 5.32), 5.24 (1H, d, OH, J ¼ 5.05), 5.01 (1H, t, OH,
J ¼ 4.95), 4.90 (1H, d, H-1; J1,2 ¼ 3.27), 4.71 (1H, dd, H-2; J2,3 ¼ 10.00), 3.79
(1H, ddd, H-3; J3,4 ¼ 9.17), 3.73–3.61 (1H, m, H-5; J5,6 ¼ 4.91), 3.54 (1H, ddd,
H-4; J4,5 ¼ 9.28), 3.52–3.36 (2H, m, H-6; Jgem ¼ 11.21), 3.25 (3H, s, CH3).
Anal. calcd. for C14H17NO9: C 48.98; H 4.99; N 4.08. Found C 49.00; H
4.95; N 4.10. FABMS (-) m/z 343 (100%, M2), 193 (54).
Methyl 2-O-2-nitrobenzoyl-a-D-glucopyranoside (8c)
m.p. 123–1258C, 70% yield. 1H-NMR (DMSO) d (ppm): 8.15–7.10 (4H,
m, Ar), 5.41 (1H, d, OH, J ¼ 5.28), 5.32 (1H, d, OH, J ¼ 5.00), 5.06 (1H, t,
OH, J ¼ 5.12), 4.85 (1H, d, H-1; J1,2 ¼ 3.45), 4.75 (1H, dd, H-2;
J2,3 ¼ 9.90), 3.70 (1H, ddd, H-3; J3,4 ¼ 9.80), 3.50 (1H, ddd, H-4;
J4,5 ¼ 9.25), 3.48–3.37 (1H, m, H-5; J5,6 ¼ 5.25), 3.34–3.23 (2H, m, H-6,
Jgem ¼ 11.39), 3.20 (3H, s, CH3). Anal. calcd. for C14H17NO9: C 48.98; H
4.99; N 4.08. Found C 48.80; H 5.00; N 4.10. FABMS (-) m/z 343 (100%,
M2), 193 (67).

Regioselective Acylation of Secondary Hydroxyl
4215
Methyl 2-O-2-chlorobenzoyl-a-D-glucopyranoside (8d)
m.p. 154–1558C, 77% yield. 1H-NMR (DMSO) d (ppm): 7.88–7.12 (4H,
m, Ar), 5.38 (1H, d, OH, J ¼ 5.73), 5.26 (1H, d, OH, J ¼ 5.86), 4.98 (1H, d,
H-1; J1,2 ¼ 3.64), 4.71 (1H, dd, H-2; J2,3 ¼ 9.95), 4.47 (1H, t, OH, J ¼ 5.80),
3.76 (1H, ddd, H-3; J3,4 ¼ 8.79), 3.74–3.67 (1H, m, H-5; J5,6 ¼ 5.82), 3.54
(1H, ddd, H-4; J4,5 ¼ 9.57), 3.52–3.41 (2H, m, H-6, Jgem ¼ 11.75), 3.38
(3 H, s, CH3). Anal. calcd. for C14H17ClO7: C 50.38; H 5.15; Cl 10.66.
Found C 50.50; H 5.15; Cl 10.60. FABMS (-) m/z 331 (37%, M-H)2,
193 (100).
Methyl 2-O-1-naphthyl acetyl-a-D-glucopyranoside (8e)
m.p. 120–1218C, 75% yield. 1H-NMR (DMSO) d (ppm): 8.00–7.40 (7H,
m, Ar), 5.36 (1H, d, OH, J ¼ 5.40), 5.25 (1H, d, OH, J ¼ 5.32), 4.69 (1H, d,
H-1; J1,2 ¼ 3.60), 4.60 (1H, t, OH, J ¼ 5.19), 4.48 (1H, dd, H-2; J2,3 ¼ 9.73),
3.74 (1H, ddd, H-3; J3,4 ¼ 9.28), 3.70 (1H, ddd, H-4; J4,5 ¼ 9.54), 3.67–3.56
(1H, m, H-5; J5,6 ¼ 5.04), 3.51–3.41 (2H, m, H-6, Jgem ¼ 11.14), 3.36 (3H, s,
CH3). Anal. calcd. for C19H22O7: C 62.97; H 6.12. Found C 63.00; H 6.10.
FABMS (-) m/z 361 (23.5%, M-H)2, 193 (100).
ACKNOWLEDGMENTS
Grants from Consiglio Nazionale delle Ricerche (CNR) are gratefully
acknowledged.
REFERENCES
1. Hurford, J.R. Developments in Food Carbohydrates. Lee, C.K., ed.
Applied Science Publishers: Barking, UK, 1980, 327–334.
2. Attwood, D.; Florence, A.T. Surfactant Systems. Their Chemistry, Phar-
macy and Biology. Chapman and Hall: London, UK, 1983.
3. Lichtenthaler, F.W., ed. Carbohydrates as Organic Raw Materials.
VCH: Weiheim, Germany, 1991.
4. Ringsdorf, H.; Schlarb, B.; Venzmer, J. Angew. Chem. Int. Ed. Engl.
1988, 27, 113. Lawrence, M. J. Chem. Soc. Rev. 1994, 417.
5. Le Bec., C.; Huynh-Dinh, T. Synthesis of lipophilic phosphate triester
derivatives of 5-fluorouridine and arabinocytidine as anticancer prodrugs.
Tetrahedron Lett. 1991, 32, 6553.

4216
Dalpozzo et al.
6. Dasgupta, F.; Hay, G.W.; Szareck, W.A.; Shilling, W.L. Acetylation of
carbohydrates by transesterification using ethyl acetate and sodium
hydride. Carbohydr. Res. 1983, 114, 153.
7. Plusquellec, D.; Baczko, K. Sugar chemistry without protecting groups: a
novel regioselective synthesis of 6-O-acyl-D-glucopyranoses and methyl-
6-O-acyl-a-D-glucopyranosides. Tetrahedron Lett. 1987, 28, 3809.
Baczko, K.; Plusquellec, D. Sugar chemistry without protecting groups-
III. A facile chemical synthesis of 6-O-acyl-D-glycopyranoses and
methyl-6-O-acyl-d-glycopyranosides. Tetrahedron 1991, 47, 3817.
8. De Luca, D.; De Nino, A.; Liguori, A.; Procopio, A.; Sindona, G. Nonio-
nic surfactants regioselective synthesis of fatty acid esters of a- and
b-glucopyranose. Lipids 1997, 32 (5), 559.
9. De Nino, A.; Liguori, A.; Procopio, A.; Roberti, E.; Sindona, G. A novel
approach to the synthesis of lipophilic thymidinemonophosphogluco-
pyranosides as drug delivery systems. Carbohydr. Res. 1996, 286, 77.
10. Brown, J.M.; Christodolou, C.; Reese, C.B.; Sindona, G. Two new pro-
tected acyl protecting groups for alcoholic hydroxy functions. J. Chem.
Soc., Perkin Trans. 1. 1984, 1785.
11. Liguori, A.; Perri, E.; Sindona, G.; Uccella, N. Chemo and regioselec-
tive acylation of deoxyribonucleosides by means of N,N-bis-(2-oxo-
oxazolidin-3-yl) phosphorodiammidic chloride (BOPDC). Tetrahedron
1988, 44, 229–234.
12. Liguori, A.; Procopio, A.; Romeo, G.; Sindona, G.; Uccella, N.
Regioselective acylation of methyl a-D-glucopyranoside and methyl
a-D-mannopyranoside by means of bis(2-oxooxazolidin-3-yl)phosphinic
chloride (BOP-Cl). J. Chem. Soc. Perkin Trans. 1. 1993, 1783.
13. De Nino, A.; Leggio, A.; Liguori, A.; Maiuolo, L.; Napoli, A.; Procopio, A.;
Roberti, E.; Siciliano, C.; Sindona, G. Regioselective synthesis of amino-
acylthymidines by direct esterification with bis (2-oxooxazolidin-3-yl)
phosphinic chloride (BOP-Cl). Gazz. Chim. Ital. 1996, 126, 605.
`
14. Cabre, J.; Palomo, A.L. New experimental strategies in amide syn-
thesis using N,N-Bis[2-oxo-3-oxazolidinyl]phosphorodiamidic chloride.
Synthesis 1984, 413.
15. Ohle, H.; Tessmar, K. Syntheses with 5,6-anhydroacetoneglucose. (VI).
6-alkyl ethers of glucose. Ber. 1938, 71B, 1843 (Chem. Abst. 32: 9043).
16. Chaudhary, S.K.; Hernandez, O. A simplified procedure for the prep-
aration of triphenylmethylethers. Tetrahedron Lett. 1979, 20, 95.
17. Weinmann, G.; Khorana, H.G. Studies on polynucleotides. XIII.1 Stepwise
synthesis of deoxyribo-oligonucleotides. An alternative general approach
and the synthesis of thymidine di-, tri- and tetranucleotides bearing
300-posphomonoester end groups2. J. Am. Chem. Soc. 1962, 84, 419.

Regioselective Acylation of Secondary Hydroxyl
4217
18. Williams, J.M.; Richardson, A.C. Selective acylation of pyranoside—I.
Benzoylation of methyl a-D-glycopyranosides of mannose, glucose and
galactose. Tetrahedron 1967, 23, 1369. Peri, F.; Cipolla, L.; Nicotra, F.
Tin-mediated regioselective acylation of unprotected sugars on solid
phase. Tetrahedron Lett. 2000, 41, 8587.
19. Therisold, M.; Klibanov, A.M. Facile enzymatic preparation of monoacy-
lated sugars in pyridine. J. Am. Chem. Soc. 1986, 108, 5638.
Therisold, M.; Klibanov, A.M. Regioselective acylation of secondary
hydroxyl groups in sugars catalyzed by lipases in organic solvents.
J. Am. Chem. Soc. 1987, 109, 3977. MacManus, D.A.; Vulfson, E.N.
Substituent effects on the regioselectivity of enzymatic acylation of
6-O-alkylglycopyranosides using Pseudomonas cepacia lipase. Carbo-
hydr. Res. 1995, 279, 281.
20. Bessodes, N.; Komiotis, D.; Antonakis, K. Rapid and selective detrityla-
tion of primary alcohols using formic acid. Tetrahedron Lett. 1986, (27),
¨
579. Koster, H.; Sinha, N.D. Dialkyl aluminium chloride: a reagent for
removal of trityl group from trityl ethers of deoxynucleosides, deoxynu-
cleotides, and oligodeoxynucleotides. Tetrahedron Lett. 1982, 23, 2641.
Jackson, A.E.; Johnstone, R.A.W. Rapid, selective removal of benzylox-
ycarbonyl groups from peptides by catalytic transfer hydrogenation.
Synthesis 1976, 685; (d) Brieger, G.; Nestrick, T. J. Catalytic transfer
hydrogenation. Chem. Rev. 1974, 74, 567.
Received in the UK January 19, 2004