Synthesis of 3-C-(6-O-acetyl-2,3,4-tri-O-benzyl-α-D-mannopyranosyl)-1-propene: A caveat

Article abstract of DOI:10.1016/S0008-6215(02)00206-9

During the preparation of 3-C-(6-O-acetyl-2,3,4-tri-O-benzyl-α-D-mannopyranosyl)-1-propene, using a published Sakurai-type reaction on the parent methyl glycoside, some observations were made on the sensitivity to reaction conditions that were not previously reported. This Note presents the study of this allylation reaction followed by acetolysis, which ultimately led to the best conditions to obtain the C-glycoside, and on further transformations to yield the corresponding aldehydic and acidic derivatives.

Full text of DOI:10.1016/S0008-6215(02)00206-9

Carbohydrate Research 337 (2002) 1769–1774
www.elsevier.com/locate/carres
Note
Synthesis of
3-C-(6-O-acetyl-2,3,4-tri-O-benzyl-a-
D
-mannopyranosyl)-1-propene:
a caveatꢀ
Christian Girard,* Marie-Laure Miramon, Tanguy de Solminihac, Jean Herscovici
Laboratoire de Chimie Bioorganique et de Biotechnologie Mole´culaire et Cellulaire, UMR 7001 CNRS, Ecole Nationale Supe´rieure de Chimie de
Paris, F-75005 Paris, France
Received 16 April 2002; accepted 8 July 2002
Abstract
During the preparation of 3-C-(6-O-acetyl-2,3,4-tri-O-benzyl-a-D-mannopyranosyl)-1-propene, using a published Sakurai-type
reaction on the parent methyl glycoside, some observations were made on the sensitivity to reaction conditions that were not
previously reported. This Note presents the study of this allylation reaction followed by acetolysis, which ultimately led to the best
conditions to obtain the C-glycoside, and on further transformations to yield the corresponding aldehydic and acidic derivatives.
© 2002 Elsevier Science Ltd. All rights reserved.
Keywords: Silayl Lewisx analogs; C-Glycosylic compound, synthesis; Sakurai allylation; Acetolysis
C-Glycosylic compounds, commonly referred to as
C-glycosides, are the 1-deoxy analogues of natural
products1 and have shown high potencies in biological
pathways involving sugars showing various activities.2
For other purposes, C-glycosides have also been used
as scaffolds to synthesize analogues of more complex
sugars (oligosaccharides). As an example, C-glycosides
The synthesis started with a classical benzylation of
-mannopyran-
the commercially available methyl a-
D
oside (1) in moderate yield (Scheme 1).4,5 A better
procedure was the treatment of the sugar with sodium
hydride (1.5 equiv per hydroxyl group), followed by
benzylation with benzyl bromide (1.1 equiv per hy-
droxyl) in the presence of a catalytic amount of tetra-
of D-mannose were a key structure for the development
butylammonium iodide (0.1 equiv).
workup procedure gave the desired methyl 2,3,4,6-tetra-
-mannopyranoside (2) in an excellent yield
A simplified
of several sialyl Lewisx (sLex) analogs with high affinity
for human E-selectin.3 During the course of our studies
on interactions between sLex mimics and E-selectin, we
needed to prepare model compounds that were already
known for their activity in order to ascertain the re-
quired approaches and tests. We selected derivatives of
C-mannose with a chemical differentiation between the
C-6 position of the original sugar and its C-1 chain.
The preparation of these derivatives involved a key
intermediate; the 3-C-(6-O-acetyl-2,3,4-tri-O-benzyl-a-
O-benzyl-a-
D
(97%), even on a 20-g scale.
The following step implied the formation of the
desired C-mannoside by a Sakurai-type general allyla-
tion reaction on the methyl glycoside 2 (Scheme 2).6,7
Literature precedents reported that treatment of the
methyl glycoside 2 with allyltrimethylsilane in acetoni-
trile in the presence of trimethylsilyl triflate gave access
to the a-allylated C-mannoside 3 in 87% yield. When
acetic anhydride was added before workup, an in situ
D
-mannopyranosyl)propene (4).
ꢀ IUPAC name: 9-O-acetyl-4,8-anhydro-5,6,7-tri-O-benzyl-
1,2,3-trideoxy-D-glycero-D-galacto-non-1-enitol.
* Corresponding author. Tel.: +33-1-44276722; fax: +33-
1-53101292
E-mail address: cgirard@ext.jussieu.fr (C. Girard).
Scheme 1. Benzylation of methyl a-D-mannopyranoside (1).
0008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(02)00206-9

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C. Girard et al. / Carbohydrate Research 337 (2002) 1769–1774
Scheme 2. Sakurai-type reaction on the methyl glycoside 2 to
obtain the C-allyl mannosides 3 or 4.
acetolysis took place to generate the 3-C-(6-O-acetyl-
2,3,4-tri-O-benzyl-a- -mannopyranosyl)propene (4) in
D
83% yield.8,9
However, in our hands this reaction was found to be
quite delicate and sensitive. Our first attempt using the
described procedure led to two products, having only a
small Rf difference on silica gel. The two compounds
were obtained in 76 and 22% isolated yields and iden-
tified as the desired 6%-O-acetyl derivative 4, together
with the 6%-O-benzyl analogue 3.
The initial reaction conditions (Entry 1, Table 1),
using 2.1 equiv of allyltrimethylsilane and 0.5 equiv of
trimetylsilyl triflate at 4 °C, gave 3:4 in a ratio of 3.5:1,
in 98% yield. Adding more allyltrimethylsilane (2.7
equiv) at room temperature dropped the ratio of 3:4 to
1.8:1 (88% yield). When the reactions were conducted
on larger scale (Entries 3 and 4), the ratios showed the
same relation as a function of temperature. In these
cases, the 3:4 ratios were 5.3:1 and 3.3:1, for 4 °C and
room temperature, respectively (76 and 82% yields,
respectively).
Acetolysis, selective to primary benzyl ethers, is usu-
ally successfully conducted by acetic anhydride in con-
junction with strong protic or Lewis acids,10 or iodine,11
or with alkylating agents like trimethylsilyl triflate.12
This is similar to the deprotection techniques of these
ethers.13–15 Based on the fact that acetylations or ace-
tolysis can be performed with acetic anhydride in the
presence of catalytic trimethylsilyl triflate (2 mol%),16
Scheme 3. Three-step sequence for the transformation of the
C-allyl mannoside 4 into the acetic acid derivative 7.
the presence of the catalyst was thus mandatory for the
reaction to occur properly. If somehow the amount of
catalyst is reduced, or if it is in part decomposed, this
could reduce the efficiency of the acetolysis.
As a matter of fact, when we performed the allylation
reaction at 4 °C, using twice the initial amount of
trimethylsilyl triflate (Table 1, Entries 5 and 6), the
desired 6%-O-acetyl derivative 4 was isolated as the sole
product of the reaction in very good yields of 84–87%
(up to a 100 mmol; 55.5-g scale).
In order to use the C-glycoside 4 as a scaffold for
sialyl Lewisx mimics, the C-1 allylic chain needed to be
transformed to access aldehydic and acidic functionali-
ties. For this purpose, we selected a very efficient
approach that was already published.8,9 In this article,
the reactions were carried out on the 6%-O-hexadecyl
ether analogue of 4. This straightforward method was
unfortunately quite sluggish with the 6%-O-acetyl deriva-
tive 4, probably due to the nature of this acetate
substituent, when compared to the ether one, and re-
quired purification at each step (Scheme 3).
Table 1
Results of the C-allylation of the methyl a-
D-mannopyranoside 2 with allyltrimethylsilane in the presence of trimethylsilyl triflate,
followed by acetolysis with acetic anhydride a
Entry
2 (mmol)
AllylTMS (mmol (equiv))
TMSOTf (mmol (equiv))
3 (%) d
4 (%) d
1 b
2 c
3 b
4 c
5 b
6 b
1.3
1.8
10.5
18
38
100
2.7 (2.1)
4.8 (2.7)
29 (2.7)
48 (2.7)
80 (2.1)
0.6 (0.5)
0.9 (0.5)
5.3 (0.5)
9.1 (0.5)
42 (1.1)
22
31
12
19
0
76
57
64
63
84
87
271 (2.7)
122 (1.2)
0
a In CH3CN at 0 °C: sequential dropwise addition of allyltrimethylsilane and TMSOTf, then 24 h reaction at the indicated
temperature, before acetolysis (excess Ac2O, 2 h) at 0 °C.
b Reaction at 4 °C.
c Reaction at room temperature.
d Isolated yields.

C. Girard et al. / Carbohydrate Research 337 (2002) 1769–1774
1771
acetyl-2,3,4-tri-O-benzyl-a-
D
-mannopyranosyl)acetic
acid (7) by Jones reagent (73%). The overall yield to
obtain the acid (7) from the mannopyranosyl alkene 4,
is thus of 51% instead of 31% for the previously de-
scribed three-step method.
Scheme 4. Direct oxidation of the C-allyl mannoside 4 to the
aldehyde 6 with osmium tetraoxide–sodium periodate.
In this Note, we present our work on the preparation
of the important basic structure for sLex mimics: the
2-C-(6-O-acetyl-2,3,4-tri-O-benzyl-a-D-mannopyran-
The dihydroxylation during 16 h of 4 with a catalytic
amount of osmium tetraoxide in the presence of N-
methylmorpholine N-oxide gave the corresponding diol
5 (only 44% yield). The periodate oxidation of the
1,2-diol 5 to the aldehyde 6 (2 h, 98%), followed by
Jones oxidation to the carboxylic acid 7 (73%), pro-
ceeded, however, more efficiently. The global yield for
the three steps was only of 31%, with the limiting step
being the osmium dihydroxylation procedure.
In order to improve the process, we decided to try
the one-pot transformation of the alkene 4 to the
corresponding aldehyde 6. The first attempt was to use
potassium permanganate on alumina, to get rid of the
toxic osmium tetraoxide procedure.17 However, the
alkene 4 was found to be quite unreactive, even after
prolonged reaction times. The other selected method
was to use a mixture of catalytic osmium tetraoxide and
excess sodium periodate, the latter being the co-oxidant
for the osmium, as well as the reagent to cleave the diol
to the aldehyde in situ (Scheme 4).18
This procedure was found to be very efficient and
fast when compared to the previous two-step approach
(Table 2). The alkene 4 was directly transformed in fair
yields (60–70%) into the aldehyde 6 in 3–16 h depend-
ing on the scale. The 15-h reaction time on the large
scale was selected to ensure a complete transformation,
since the reaction mixture became quite difficult to stir
because of the thick precipitate that formed.
When compared to the three-step procedure, the
one-pot oxidation of the alkene 4 is much better. For a
shorter (or same) time than the dihydroxylation pro-
cess, the direct passage to the aldehyde 6 is possible. In
terms of yields, the one-pot procedure gave 60–70%
yield in aldehyde 6, while the two steps only afforded
43%. The aldehyde 6 was finally oxidized to 2-C-(6-O-
osyl)acetic acid (7). For this purpose, we found the best
conditions for the initial benzylation reaction of the
starting material. A study of a Sakurai-type allylation
reaction on our substrate, followed by acetolysis,
showed that this transformation can be very sensitive.
Having found the conditions that worked in our hands,
we finally undertook the final transformation stages.
Due to the sensitivity of our derivative, the usual
three-step transformation of the alkene 4 to the acid 7
was not suitable. A one-pot oxidation using the os-
mium tetraoxide–sodium periodate system gave fast
and convenient access to the important aldehyde 6,
which was then easily transformed in carboxylic acid 7
by Jones’ reagent.
1. Experimental
General methods.—All reagents and chromato-
graphic solvents were purchased and used without
purification. N,N-Dimethylformamide (DMF) and ace-
tonitrile were dried on CaH2 and kept over molecular
sieves under nitrogen. Acetone and tetrahydrofuran
(THF) were distilled to remove stabilizants and/or im-
purities prior to use. Flash chromatographs were per-
formed on SDS 60 A C.C 35–70-mm silica gel.
Thin-layer chromatography (TLC) was developed on E.
Merck Silica Gel 60 F254 coated plastic plates and
visualized under UV or by spraying 5% H2SO4 in
EtOH. Polarimetric measurements ([h]D) were recorded
at 20 °C in distilled dichloromethane on a JASCO
P-1010 polarimeter at 589 nm (sodium lamp). Infrared
spectroscopy (FTIR) was performed on a single-beam
Nicolet 205 Fourier-transform spectrophotometer as
films on NaCl, and absorptions are reported in cm−1
.
Table 2
Direct oxidation of the alkene 4 to the aldehyde 6 using the osmium tetraoxide–sodium periodate system a
Entry
4 (mmol (g))
OsO4 (mmol (equiv))
NaIO4 (mmol (equiv))
Time (h)
6 (%) b
1
2
3
4
5
4.2 (2.2)
8.9 (4.6)
6.7 (3.5)
29 (15)
0.042 (0.01)
0.09 (0.01)
0.07 (0.01)
0.29 (0.01)
0.31 (0.01)
21.2 (5)
44.5 (5)
34 (5)
143 (5)
152 (5)
3
6
15
16
15
70
57
57
62
57
30.5 (16)
a In 1:1 THF–water.
b Isolated yields.

1772
C. Girard et al. / Carbohydrate Research 337 (2002) 1769–1774
Nuclear magnetic resonance (NMR) was recorded on a
Brucker Avance DRX 300 spectrometer in CDCl3 with
Me4Si (0.1%) as the internal standard. It was completed
by correlation (COSY, HETCOR) and differential
(DEPT) spectroscopy and chemical shift differentiation
of C-glycosides.7b,7cChemical shifts (l) are reported in
parts per million (ppm) relative to TMS (0 ppm) and
coupling constants (J) in hertz. Mass spectrometry
(Finnigan SSQ 7000, chemical ionization, NH3) and
microanalyses were done by Aventis Pharma Analytical
Services (Vitry-sur-Seine, France).
ture was kept at 0 °C, and excess Ac2O (145 mL, ꢀ1.5
mol) was carefully added dropwise (exothermic reac-
tion!), followed by 2 h stirring. The mixture was then
poured into CH2Cl2 (1 L) and stirred vigorously with
satd aq NaHCO3 (1.5 L) for 1 h (important CO2
evolution!). The phases were separated, and the organic
layer was washed with water (500 mL) and brine (500
mL), and then it was dried (MgSO4) and evaporated
under reduced pressure. The red–brown oily residue
was purified by flash chromatography on silica gel (4:1
heptane–AcOEt) to afford the C-glycoside 4 as an oil
(42.4 g, 87%): [h]D +3.990.2° (c 1, CH2Cl2); Rf 0.30
(4:1 heptane–AcOEt); IR (film, NaCl): w 3063, 3027
(wCH-Ar), 2909 (wCH-alkyl), 1737 (wCꢀO ester), 1605
(wCꢀC alkene), 1603, 1600 (wCꢀC Ar), 1496, 1454, 1368
(lCH-alkyl), 1235 (wCꢁO ester) and 1091 (wCꢁOꢁC)
Preparation of methyl 2,3,4,6-tetra-O-benzyl-h-
D-
mannopyranoside (2).—Methyl a- -mannopyranoside
D
(1, 20 g, 103 mmol) was added portionwise over 30 min
to a suspension of washed (hexanes, three times) NaH
(41.2 g of a 60% in mineral oil; 24.7 g NaH, 618 mmol,
6 equiv) in DMF (750 mL) at 0 °C under nitrogen. The
mixture was stirred at rt for 2 h. TBAI (3.8 g, 10.3
mmol, 0.1 mol%) was added to the thick mixture,
followed by dropwise addition of BnBr (79.3 g, ꢀ55
mL, 464 mmol, 4.5 equiv) over 45 min. The reaction
was stirred for 18 h, after which the mixture was
limpid. The volatiles were then evaporated in vacuo to
dryness. The isolated solid was triturated with Et2O
(3×250 mL). The combined organic extracts were
washed with water (250 mL) and brine (250 mL) before
being dried (MgSO4) and evaporated under vacuum.
The benzylated sugar 2 was isolated as an oil (55.4 g,
97%): [h]D +23.490.6° (c 1, CH2Cl2), lit.10a +28.0° (c
1, CHCl3), lit.5 +29.2° (c 1.59, CHCl3); Rf 0.26 (4:1
heptane–AcOEt); IR (film, NaCl): w 3068, 3032 (wCH-
Ar), 2909 (wCH-alkyl), 1603, 1600 (wCꢀC Ar), 1496,
1
cm−1; H NMR (300 MHz, CDCl3): l 7.34 (m, 15 H,
H-Ar), 5.74 (m, 1 H, H-2), 5.04 (m, 2 H, H-1cis,1trans),
4.77 (d, 1 H, Jgem 11.4 Hz, CH2Ph), 4.59 (m, 5 H,
CH2Ph), 4.41 (dd, 1 H, J5%,6%a 5.9, J6%a,6%b 11.7 Hz, H-6%a),
4.26 (dd, 1 H, J5%,6%b 2.6, J6%a,6%b 11.7 Hz, H-6%b), 4.10 (dt,
1 H, J1%,2%/1%,3a 1.8, J1%,3b 6.3 Hz, H-1%), 3.80 (ls, 3 H,
H-3%,4%,5%), 3.65 (dd, 1 H, J1%,2% 2.2, J2%,3% 4.4 Hz, H-2%),
2.33 (m, 2 H, H-3a,3b) and 2.07 (s, 3 H, OCOCH3-6%)
ppm; 13C NMR (75 MHz, CDCl3):
l
170.9
(OCꢀOCH3-6%), 138.2 (CIV-Ar), 134.1 (C-2), 128.5 (C-
Ar), 128.0 (C-Ar), 117.3 (C-1), 77.1 (C-3%), 75.3 (C-2%),
75.0 (C-4%), 74.0 (CH2Ph), 72.4 (C-1%,5%, CH2Ph), 71.7
(CH2Ph), 63.3 (C-6%), 34.5 (C-3) and 20.9 (OCOCH3-6%)
ppm; CIMS: m/z 534 ([M+NH4]+). Anal. Calcd for
C32H36O6: C, 74.39; H, 7.02. Found: C, 74.05; H, 7.55.
If the reaction was conducted with less TMSOTf, two
products could be detected by TLC in 7:4 heptane–
AcOEt that were identified as the 6-O-acetyl derivative
4 (Rf 0.40) and the 6-O-benzyl 3 one (Rf 0.55).
1
1455, 1358 (lCH-alkyl) and 1086 (wCꢁOꢁC) cm−1; H
NMR (300 MHz, CDCl3): l 7.29 (m, 20 H, H-Ar), 4.93
(d, 1 H, Jgem 10.8 Hz, CH2Ph), 4.83 (d, 1 H, J1,2 1.5 Hz,
H-1), 4.68 (m, 6 H, CH2Ph), 4.55 (d, 1 H, Jgem 10.8 Hz,
CH2Ph), 4.03 (pt, 1 H, J3,4/4,5 9.0 Hz, H-4), 3.93 (dd, 1
H, J2,3 3.0, J3,4 9.0 Hz, H-3), 3.84 (dd, 1 H, J1,2 1.9, J2,3
2.8 Hz, H-2), 3.79 (m, 3 H, H-5,6) and 3.37 (s, 3 H,
CH3O-1) ppm; 13C NMR (75 MHz, CDCl3): l 138.6
(CIV-Ar), 128.4 (C-Ar), 127.7 (C-Ar), 99.1 (C-1), 80.3
(C-3), 75.1 (C-4, CH2Ph), 74.8 (C-2), 73.5 (CH2Ph),
72.7 (CH2Ph), 72.2 (CH2Ph), 71.8 (C-5), 69.5 (C-6) and
54.8 (CH3O-1) ppm; CIMS: m/z 572 ([M+NH4]+).
Anal. Calcd for C35H38O6: C, 75.79; H, 6.91. Found: C,
75.77; H, 7.14.
4,8-Anhydro-5,6,7-tri-O-benzyl-1,2,3-trideoxy-
ero- -galacto-non-1-enitol (3-C-(2,3,4,6-tetra-O-benzyl-
h-
D-glyc-
D
D
-mannopyranosyl)-1-propene, 3).—[h]D +5.290.5°
(c 1, CH2Cl2), +5.3590.06° (c 7.2, CH2Cl2), lit.6
−3.0° (c 7, CHCl3); Rf 0.30 (4:1 heptane–AcOEt); IR
(film, NaCl): w 3063, 3029 (wCH-Ar), 2907 (wCH-alkyl),
1641 (wCꢀC alkene), 1604, 1586 (wCꢀC Ar), 1496, 1454,
1362 (lCH-alkyl) and 1095 (wCꢁOꢁC) cm−1; H NMR
1
(300 MHz, CDCl3): l 7.33 (m, 20 H, H-Ar), 5.78 (m, 1
H, H-2), 5.04 (m, 2 H, H-1cis,1trans), 4.74 (d, 1 H, Jgem
11.4 Hz, CH2Ph), 4.58 (m, 7 H, CH2Ph), 4.08 (m, 1 H,
H-1%), 3.82 (m, 4 H, H-3%,4%,5%,6%a), 3.74 (dd, 1 H, J5%,6%b
3.1, J6%a,6%b 10.1 Hz, H-6%b), 3.65 (dd, 1 H, J1%,2% 3.1, J2%,3%
4.6 Hz, H-2%) and 2.36 (m, 2 H, H-3) ppm; 13C NMR
(75 MHz, CDCl3): l 138.5 (CIV-Ar), 134.5 (C-2), 128.4
(C-Ar), 128.1 (C-Ar), 127.8 (C-Ar), 117.3 (C-1), 77.0
(C-3%), 75.3 (C-2%), 75.1 (C-4%), 73.9 (C-5%, CH2Ph), 73.4
(CH2Ph), 72.4 (C-1%), 72.2 (CH2Ph), 71.7 (CH2Ph), 69.3
(C-6%) and 34.8 (C-3) ppm; CIMS m/z 582 ([M+
NH4]+). Anal. Calcd for C37H40O5: C, 78.69; H, 7.14.
Found: C, 78.43; H, 7.58.
9-O-Acetyl-4,8-anhydro-5,6,7-tri-O-benzyl-1,2,3-
trideoxy-
acetyl-2,3,4-tri-O-benzyl-h-
D
-glycero-
D
-galacto-non-1-enitol (3-C-(6-O-
-mannopyranosyl)propene,
D
4).—To solution of sugar 2 (55.5 g, 100 mmol) in
acetonitrile (200 mL) at 0 °C under nitrogen, al-
lyltrimethylsilane (30.8 g, ꢀ42.9 mL, 270 mmol, 2.7
equiv) was added, followed after 15 min by dropwise
addition of TMSOTf (27 g, ꢀ22 mL, 121 mmol, 1.2
equiv) over 30 min. The reaction was stirred at the
same temperature for 24 h. The resulting orange mix-

C. Girard et al. / Carbohydrate Research 337 (2002) 1769–1774
1773
8-O-Acetyl-3,7-anhydro-4,5,6-tri-O-benzyl-2-deoxy-
glycero- -galacto-octose (2-C-(6-O-acetyl-2,3,4-tri-O-
benzyl-h- -mannopyranosyl)acetaldehyde, 6).—Ac-
D
-
The resulting oil was flash chromatographed on silica
(1:3:0.01 heptane–AcOEt–AcOH) to afford the acid 7
as a colorless oil (18.0 g, 73%): [h]D +18.890.4° (c 1,
CH2Cl2); Rf 0.20 (7:4 heptane–AcOEt); IR (film,
NaCl): w 3043 (large, wCO2H) 3086, 3064, 3027 (wCH-
Ar), 2925, 2868 (wCH-alkyl), 1736 (wCꢀO ester), 1714
(wCꢀO acid), 1496, 1450, 1373 (lCH-alkyl), 1240
D
D
cording to Xie et al.,18 the 6-O-acetyl alkene derivative
4 (15 g, 29 mmol) in 1:1 THF–water (550 mL) was
treated with NaIO4 (30.5 g, 143 mmol, 5 equiv) and
OsO4 (2.5% wt. solution in t-BuOH, 3.6 mL, ꢀ74 mg
OsO4, 0.29 mmol) at rt, in a flask equipped with a
rubber septum. The mixture was left stirring overnight
(16 h) in order to insure a complete tranformation. The
mixture was then diluted with water to solubilize the
thick, white precipitate and extracted with CH2Cl2 (3×
350 mL). The combined organic extracts were washed
with brine (350 mL), dried (MgSO4) and evaporated in
vacuo. The crude oil was purified by flash chromatogra-
phy on silica (4:1 to 3:1 heptane–AcOEt) to give the
aldehyde 6 as an oil (9.3 g, 62%): [h]D +37.290.4° (c
1, CH2Cl2); Rf 0.23 (7:4 heptane–AcOEt); IR (film,
NaCl): w 3066, 3027 (wCH-Ar), 2907 (wCH-alkyl), 2868,
2736 (wCH-aldehyde), 1731 (wCꢀO ester/aldehyde),
1603, 1600 (wCꢀC Ar), 1496, 1455, 1363 (lCH-alkyl),
1230 (wCꢁO ester) and 1091 (wCꢁOꢁC) cm−1; 1H NMR
(300 MHz, CDCl3): l 9.70 (ls, 1 H, H-1), 7.34 (m, 15 H,
H-Ar), 4.68 (dd, 1 H, J5%,6%a 8.2, J6%a,6%b 11.5 Hz, H-6%a),
4.58 (m, 1 H, H-1%), 4.49 (m, 6 H, CH2Ph), 4.07 (dd, 1
H, J5%,6%b 3.8, J6%a,6%b 11.5 Hz, H-6%b), 3.98 (m, 1 H, H-5%),
3.80 (dd, 1 H, J 3.0, J 4.7 Hz, H-3%), 3.61 (m, 2 H,
H-2%,4%), 2.71 (ddd, 1 H, J1,2a 1.6, J1%,2a 5.7, J2a,2b 16.2,
H-2a), 2.55 (ddd, 1 H, J1,2b 2.9, J1%,2b 8.4, J2a,2b 16.4,
H-2b) and 2.06 (s, 3 H, OCOCH3-6%) ppm; 13C NMR
(75 MHz, CDCl3): l 200.7 (C-1), 170.9 (OCꢀOCH3-6%),
137.8 (CIV-Ar), 128.6 (C-Ar), 128.1 (C-Ar), 75.9 (C-2%),
74.7 (C-4%), 73.6 (C-3%,5%), 73.0 (CH2Ph), 72.6 (CH2Ph),
71.6 (CH2Ph), 65.8 (C-1%), 62.0 (C-6%), 45.6 (C-2) and
20.9 (OCOCH3-6%) ppm; CIMS: m/z 536 ([M+NH4]+).
Anal. Calcd for C31H34O7: C, 71.80; H, 6.61. Found: C,
71.59; H, 6.36.
1
(wCꢁO ester) and 1112 (wCꢁOꢁC) cm−1; H NMR (300
MHz, CDCl3): l 7.30 (m, 15 H, H-Ar), 4.52 (m, 8 H,
H-1%,6%a,CH2Ph), 4.18 (dd, 1 H, J5%,6%b 3.7, J6%a,6%b 11.9
Hz, H-6%b), 4.00 (m, 1 H, H-5%), 3.80 (dd, 1 H, J 2.9, J
5.3 Hz, H-3%), 3.65 (m, 2 H, H-2%,4%), 2.76 (dd, 1 H, J1%,2a
4.6, J2a,2b 15.8, H-2a), 2.55 (dd, 1 H, J1%,2b 8.5, J2a,2b
15.7, H-2b) and 2.04 (s, 3 H, OCOCH3-6%) ppm; 13C
NMR (75 MHz, CDCl3):
l 175.3 (C-1), 170.4
(OCꢀOCH3-6%), 137.8 (CIV-Ar), 128.6 (C-Ar), 128.0
(C-Ar), 75.5 (C-2%), 74.7 (C-4%), 74.4 (C-5%), 73.6 (C-3%),
72.9 (CH2Ph), 71.6 (CH2Ph), 67.6 (C-1%), 62.2 (C-6%),
36.4 (C-2) and 20.6 (OCOCH3-6%) ppm; CIMS: m/z 552
([M+NH4]+). Anal. Calcd for C31H34O8: C, 69.65; H,
6.41. Found: C, 69.35; H, 6.00.
Acknowledgements
Financial support from CNRS, MENRT and Aven-
tis Pharma is gratefully acknowledged. This research
was also supported by an SESAME program, as well as
by a generous Aventis fellowship to M.-L. Miramon.
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