A general route to 4-C-branched sugars. Synthesis of methyl α-caryophylloside

Article abstract of DOI:10.1016/S0008-6215(01)00101-X

The total synthesis of methyl 3,6-dideoxy-4-C-(D-altro-1,3,4,5 tetrahydroxyhexyl)-α-D-xylo-hexopyranoside, the methyl glycoside of the recently isolated 4-C-branched sugar caryophyllose, has been completed in a stereoselective and convergent manner. The synthesis of this dodecose relies on the diiodosamarium mediated coupling of two six-carbon fragments: a cyclic ketone and an acid chloride.

Full text of DOI:10.1016/S0008-6215(01)00101-X

www.elsevier.nl/locate/carres
Carbohydrate Research 332 (2001) 241–247
A general route to 4-C-branched sugars. Synthesis of
methyl a-caryophylloside
Jacques Prandi*
Institut de Pharmacologie et de Biologie Structurale du CNRS, 205 route de Narbonne, F-31077 Toulouse, France
Received 23 February 2001; accepted 29 March 2001
Abstract
The total synthesis of methyl 3,6-dideoxy-4-C-(
D
-altro-1,3,4,5 tetrahydroxyhexyl)-a-D-xylo-hexopyranoside, the
methyl glycoside of the recently isolated 4-C-branched sugar caryophyllose, has been completed in a stereoselective
and convergent manner. The synthesis of this dodecose relies on the diiodosamarium mediated coupling of two
six-carbon fragments: a cyclic ketone and an acid chloride. © 2001 Elsevier Science Ltd. All rights reserved.
Keywords: 4-C-Branched monosaccharide; Diiodosamarium; Deoxy sugar
1. Introduction
pling of a cyclic ketone 6 (Scheme 2) with an
acid chloride, precursor of the side chain of
the sugar. Following our preliminary commu-
nication on the implementation of this strat-
egy for the first synthesis of methyl
caryophylloside and yersiniosides,11 we now
describe our results for the preparation of
Caryophyllose is a 4-C-branched sugar
which was isolated in 1995 from the cell wall
of a strain of Pseudomonas caryophylli, the
causal agent of the bacterial wilt of carna-
tion.1 The complete structure of this dodecose
has been elucidated early after2 as 3,6,10-
methyl a-
-caryophylloside 2.†
D
trideoxy-4-C-(
D
-glycero-1-hydroxyethyl)- -
D
erythro- -gulo-decose (1) (Scheme 1) and it
D
was later shown to occur in the cell wall as an
homopolysaccharidic chain with (1“7)-a and
-b linkages.3,4 This compound belongs to the
class of 4-C-branched sugars where are also
found yersinioses A and B (Scheme 1) isolated
from two different species of Yersinia,5–7 and
tridecose 3 found in an antigenic polysacchar-
ide of Mycobacterium gastri.8,9 In the course
of our work on the full structural characteri-
zation of 3, we have developed a synthetic
approach to this class of products10 which
relies on the diiodosamarium-mediated cou-
2. Results and discussion
The preparation of the coupling partners
was straightforward as they could be easily
made from commercially available materials.
Cyclic ketone 6 was obtained in only four
steps and 40% overall yield from methyl a-
glucopyranoside via known methyl 3,6-
dideoxy-a-
-ribo-hexopyranoside 4.13,14 Selec-
D
-
D
tive monosilylation of 4 with tert-butyl-
chlorodimethylsilane (t-BDMSCl) and imida-
zole in DMF at −17 °C gave the C-4 alcohol
5 in 73% yield together with 19% of the bis-
(silylated) product. Oxidation of 5 with pyri-
* Tel.: +33-561-175485; fax: +33-561-175994.
E-mail address: prandi@ipbs.fr (J. Prandi).
† A second synthesis of caryophyllose has been published.12
0008-6215/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(01)00101-X

242
J. Prandi / Carbohydrate Research 332 (2001) 241–247
Scheme 1.
dinium chlorochromate in buffered dichloro-
methane15 gave then ketone 6 in high yield
(92%).
However, all attempts to transform the acid
11 to the acid chloride were plagued by in-
tramolecular nucleophilic attack of the C-4
oxygen atom and formation of considerable
amounts of the 5-membered lactone 15, aris-
ing from the nucleophilic attack of the C-4
oxygen atom on the activated carboxylic
group. Such reactions are well documented in
the literature.20,21 In order to decrease the
nucleophilicity of the C-4 oxygen atom, we
introduced the more bulky tert-butyl-
dimethylsilyl ether groups as protection for
the hydroxyl functions of the acid side chain.
Thus, dithioacetal 7 was treated with an ex-
cess of tert-butyldimethylsilyltriflate (TBDM-
SOTf) and pyridine in CH2Cl2 to give the
trisilylated dithioacetal 9 in 90% yield. Un-
masking of the aldehyde group was effected as
above with HgCl2 and HgO in aqueous ace-
tone and 12 was obtained in excellent yield
(93%). As the presence of acid-sensitive TB-
DMS ether groups in 12 precluded the use of
Jones reagent for the conversion of 12 to acid
13, this oxidation was carried out with
buffered potassium permanganate in tert-
butanol22 affording the acid 13 in 83% yield.
In this case, formation of the acid chloride 14
from 13 with oxalyl chloride and pyridine in
tetrahydropyran (THP), and diiodosamarium-
promoted coupling23 of the crude acid chlor-
ide 14 (1.3 equiv) with ketone 6 (1 equiv) in
THP proceeded smoothly. Expected products
were isolated in 63% yield and in a 8:1
diastereoisomeric ratio.10,11,24 Reduction of the
The six-carbon carboxylic acid, precursor of
the caryophyllose side-chain was derived from
commercially available 2,6-dideoxy-
hexose ( -digitoxose) which is also easily pre-
pared from methyl a-
-glucopyranoside.16
Thus, treatment of 2,6-dideoxy- -ribo-hexose
D
-ribo-
D
D
D
with an excess of ethanethiol and concentrated
hydrochloric acid17 for 3 h at 0 °C gave the
diethyl dithioacetal 7 in 81% yield. Perbenzy-
lation with an excess of benzyl bromide and
sodium hydride in DMF, followed by
dithioacetal hydrolysis with mercuric oxide
and mercuric chloride in aqueous acetone18
gave the aldehyde 10 (69%). Finally, the car-
boxylic acid 11 was obtained in 92% yield
from oxidation of 10 with Jones reagent19.
major
diastereomer
16
in
chelating
conditions25 with sodium borohydride in
methanol at 0 °C was very slow but the 1%S
alcohol 17 was eventually obtained in 73%
yield after 24 h at room temperature. Com-
pared to our previous results on related com-
pounds,10,11
a
slight decrease of the
diastereoselectivity of the reduction was ob-
served (1%S/1%R: 5:1) and this could be related
Scheme 2.

J. Prandi / Carbohydrate Research 332 (2001) 241–247
243
to the higher reaction temperature. Determi-
nation of the absolute configuration of the
new C-1% stereocenter was made according to
the procedure used for the synthesis of 310 and
the result was fully consistent with reported
examples by us and others.12 Removal of all
protecting groups was achieved in one step
with dilute hydrochloric acid in aqueous THF
oside (1.09 g, 6.7 mmol) and imidazole (0.91 g,
13.4 mmol) in DMF (10 mL) was treated at
−17 °C with tert-butylchlorodimethylsilane
(1.01 g, 6.7 mmol). After 40 min, a further
portion of t-BDMSCl (335 mg, 2.2 mmol) was
added and the mixture was left for 1 h at
−17 °C before quenching with a 5% NaHCO3
solution. CH2Cl2 extraction and chromatogra-
phy (3:1 petroleum ether–EtOAc) gave 5 as a
colorless oil (1.37 g, 73%). [h]2D0 +80° (c 1.00,
and methyl a- -caryophylloside 2 was isolated
D
in 77% yield. Comparison with the natural
product1 and full characterization were done
on the pentaacetylated derivative 18 obtained
in 82% yield after acetylation with acetic an-
hydride in pyridine.
1
CHCl3); IR (liquid film): w 3441 cm−1; H
NMR (CDCl3): l 4.48 (d, 1 H, J1,2 3.5 Hz,
H-1), 3.78 (ddd, 1 H, J2,3ax 11.5, J2,3eq 5.0 Hz,
H-2), 3.53 (dq, 1 H, J5,4 9.0, J5,6 6.0 Hz, H-5),
3.42 (s, 3 H, OCH3), 3.28 (m, 1 H, J4,3ax 11.5,
J4,OH 6.5, J4,3eq 4.5 Hz, H-4), 2.03 (ddd, 1 H,
J3eq,3ax 11.5 Hz, H-3eq), 1.82 (m, 1 H, H-3ax),
1.47 (d, 1 H, OH), 1.25 (d, 3 H, H-6), 0.89 (s,
9 H, C(CH3) ), 0.08 (s, 6 H, Si(CH3)2); 13C
NMR (CDCl33): l 99.16 (C-1), 71.14 (C-4),
68.76 (C-5), 68.39 (C-2), 55.10 (OCH3), 36.70
(C-3), 25.80 (C(CH3)3), 18.23 (C(CH3)3), 17.38
(C-6), −4.69 and −4.72 (Si(CH3)2); CIMS
(NH3): m/z 277 [M+H]+. Anal. Calcd for
C13H28O4Si: C, 56.48; H, 10.21. Found: C,
56.14; H, 10.22.
3. Conclusion
The diiodosamarium mediated coupling of
an acid chloride and a ketone proved to be
highly valuable for the short (only seven steps
along the longest linear route) and convergent
synthesis of the branched sugar caryophyllose.
This methodology should find general use for
the synthesis of other a-hydroxylated C-
branched sugars.26
Methyl
dideoxy-h-
2-O-tert-butyldimethylsilyl-3,6-
-erythro-hexopyranosid-4-ulose
D
4. Experimental
(6).—A suspension of pyridinium chlorochro-
mate (5.30 g, 24.6 mmol), NaOAc (2.02 g,
General methods.—All reactions were per-
formed under Ar in anhyd purified solvents.
NMR spectra were recorded on Bruker DPX
250 or AMX 250 (operating at 250 MHz for
1H and at 62.9 MHz for 13C) spectrometers,
chemical shifts are expressed in ppm, from
,
24.6 mmol) and 3 A molecular sieves in
CH2Cl2 (60 mL) was stirred for 30 min at rt
before addition of a solution of 5 (1.94 g, 7.02
mmol) in CH2Cl2 (5 mL). After 30 min at rt,
Et2O was added, the mixture was filtered on
Celite and the filtrate evaporated. Chromatog-
raphy (7:1 heptane–EtOAc) gave ketone 6 as
a colorless oil (1.78 g, 92%). [h]2D0 +98° (c
1
Me4Si for H and 13C spectra. Optical rota-
tions were recorded at 20 °C on a Perkin–
Elmer 241 polarimeter. IR spectra were
recorded on a Perkin–Elmer 1600 series FTIR
spectrometer. Mass spectra were obtained at
the University of Orle´ans (France) with a
Ribermag R10–10 spectrometer, products
were chemically ionized with NH3 (CI/NH3).
Elemental analysis were carried out at the
Service Central de Microanalyse du CNRS at
Vernaison or at the Laboratoire de Chimie de
Coordination du CNRS at Toulouse (France).
Methyl 2-O-tert-butyldimethylsilyl-3,6-di-
1.20, CHCl3); IR (liquid film): w 1728 cm−1
;
1H NMR (CDCl3): l 4.70 (d, 1 H, J1,2 3.5 Hz,
H-1), 4.14 (q, 1 H, J5,6 6.5 Hz, H-5), 4.11
(ddd, 1 H, J2,3ax 10.5, J2,3eq 5.5 Hz, H-2), 3.53
(s, 3 H, OCH3), 2.75 (dd, 1 H, J3ax,3eq 15.5 Hz,
H-3ax), 2.60 (dd, 1 H, H-3eq), 1.27 (d, 3 H,
H-6), 0.89 (s, 9 H, C(CH3)3), 0.09 and 0.08 (2s,
2×3 H, Si(CH3) ); 13C NMR (CDCl3): l
2
206.34 (C-4), 99.03 (C-1), 69.74 (C-5), 69.01
(C-2), 55.73 (OCH3), 43.70 (C-3), 25.58
(C(CH3)3), 17.99 (C(CH3)3), 14.33 (C-6),
−4.92 and −4.95 (Si(CH3)2); CIMS (NH3):
deoxy-h-
D
-ribo-hexopyranoside (5).—A solu-
-ribo-hexopyran-
tion ofmethyl3,6-dideoxy-a-
D

244
J. Prandi / Carbohydrate Research 332 (2001) 241–247
Table 1
1H NMR chemical shifts (l), apparent multiplicities and coupling constants in Hz for compounds 7, 9, 10, 12 and 13
H
1
7
9
10
12
13
4.07 dd
J1,2a 8.0
J1,2b 6.5
2.25 ddd
J2a,2b 14.5
J2a,3 2.5
2.04 ddd
J2b,3 9.5
4.01 ddd
J3,4 6.5
3.91 dd
9.67 dd
J1,2a 2.5
J1,2b 2.0
2.74 ddd
J2a,2b 17.0
J2a,3 7.0
2.54 ddd
J2b,3 4.5
4.21 ddd
J3,4 4.0
9.85 dd
J1,2a 3.5
J1,2b 2.0
2.65 ddd
J2a,2b 16.5
J2a,3 6.0
2.49 ddd
J2b,3 4.5
4.40 m
J1,2a 11.5
J1,2b 3.2
1.82 ddd
J2a,2b 15.0
J2a,3 2.0
2.11 ddd
J2b,3 9.5
4.15 m
2a
2.66–2.47
2.66–2.47
2.66–2.47
2.66–2.47
2b
3
4.35 m
J3,4 3.0
4
3.45 dd
J4,5 6.0
3.47 dd
J4,3 1.5
3.69 dd
J4,5 6.0
3.55 dd
J4,5 6.0
3.53 dd
J4,3 3.0
J4,5 6.0
J4,5 6.0
5
6
3.96 m
1.27 d
3.69 m
1.13 d
3.61 m
1.25 d
3.69 m
1.15 d
3.70 m
1.14 d
J6,5 6.0
J6,5 6.0
J6,5 6.0
J6,5 6.0
J6,5 6.0
Other
Signals
2×SCH2
2.74, 2.62
2×SCH2CH3
1.26, 1.27
2×SCH2
2.76–2.49
2×SCH2CH3
1.25, 1.24
Ar 7.40–7.20
6×PhCH2O
4.80–4.40
3×t-BuSi 0.89
6×MeSi
0.14–0.05
3×t-BuSi
0.90–0.87
6×MeSi
0.15–0.06
3×t-BuSi 0.91–0.90
6×MeSi 0.14–0.08
m/z 292 [M+NH4]+. No satisfactory analyti-
mL) and treated at 0 °C with TMSOTf (0.41
mL, 1.75 mmol). After 24 h at rt, the mixture
was hydrolyzed and extracted with CH2Cl2.
Chromatography (10:1 petroleum ether–tolu-
ene) gave the product as a clear oil (211 mg,
cal data could be obtained for this product.
2,6-Dideoxy-
D
-ribo-hexose diethyl dithioac-
-ribo-hexose (297 mg,
etal (7).—2,6-Dideoxy-
D
2.00 mmol) was suspended in ethanethiol (0.8
mL) at 0 °C. Concd HCl (0.35 mL of a 36%
aq solution) was added and the reaction mix-
ture was left at 0 °C for 3 h before neutraliza-
tion with solid K2CO3 (340 mg, 2.46 mmol)
and dilution with MeOH. The mixture was
filtered, the precipitate washed twice with
MeOH and the filtrate evaporated. The
residue was taken up in CH2Cl2, the cloudy
suspension was filtered, and the filtrate evapo-
rated. Chromatography (10:1 CH2Cl2–
MeOH) gave a clear oil (414 mg, 81%). [h]D20
1
90%). [h]2D0 −22° (c 1.14, CHCl3); H NMR
data see Table 1; 13C NMR (CDCl3): l 82.15
(C-4), 71.59 (C-3), 69.72 (C-5), 47.85 (C-1),
39.39 (C-2), 26.10, 26.05 (C(CH3)3), 24.28,
23.83 (SCH2CH3), 20.71 (C-6), 18.38, 18.13,
18.03 (C(CH3)3), 14.73, 14.17 (SCH2CH3),
−3.50, −3.67, −4.15, −4.19, −4.66 (2)
(CH3Si). Anal. Calcd for C28H64O3S2Si3: C,
56.31; H, 10.80. Found: C, 56.56; H, 10.91.
3,4,5 - Tri - O - benzyl - 2,6 - dideoxy -
D
- ribo-
hexose (10).—Compound 7 (414 mg, 1.63
mmol) was dissolved in DMF (12 mL) and
treated at 0 °C with BnBr (1.16 mL, 9.8
mmol) and NaH (0.59 g of a 60% dispersion
in mineral oil, 14.7 mmol, washed twice with
petroleum ether). The reaction was left for 2 h
at rt before treatment with MeOH.
Dichloromethane extraction and chromatog-
raphy (8:1 heptane–EtOAc) gave 8 as a clear
oil (508 mg, 59%) [h]2D0 −12° (c 1.20, CHCl3).
This product was taken up in acetone (16 mL)
and water (1.6 mL) and treated at rt with
1
−24° (c 1.00, CHCl3); H NMR data see
Table 1; 13C NMR (CDCl3): l 76.89 (C-4);
71.94 (C-3); 69.20 (C-5); 48.41 (C-1); 38.61
(C-2); 24.27 and 23.89 (SCH2CH3); 18.65 (C-
6); 14.35 (SCH2CH3). Anal. Calcd for
C10H22O3S2: C, 47.21; H, 8.71. Found: C,
47.48; H, 8.74.
3,4,5 - Tri - O - tert - butyldimethylsilyl - 2,6-
dideoxy- -ribo-hexose diethyl dithioacetal
D
(9).—Compound 7 (100 mg, 0.39 mmol) was
dissolved in CH2Cl2 (5 mL) and pyridine (0.48

J. Prandi / Carbohydrate Research 332 (2001) 241–247
245
(CDCl3): l 178.55 (C-1), 81.46 (C-4), 70.45
(C-3), 69.74 (C-5), 37.84 (C-2), 26.09, 25.92(2)
(C(CH3)3), 20.13 (C-6), 18.34, 18.03, 17.99
(C(CH3)3), −4.06, −4.34, −4.40, −4.53,
−4.67, −4.94 (CH3Si). Anal. Calcd for
C24H54O5Si3: C, 56.86; H, 10.74. Found: C,
57.27; H, 10.41.
HgCl2 (575 mg, 1.21 mmol) and HgO (251
mg, 1.16 mmol). After 40 min, the reaction
mixture was filtered on Celite and the filtrate
evaporated. The residue was taken up in
CH2Cl2 and washed with NH4Cl solution.
Chromatography (4:1 petroleum ether–
EtOAc) gave 10 as a clear oil (281 mg, 69%).
[h]2D0 −19° (c 1.00, CHCl3); IR (liquid film): w
Methyl
dideoxy-4-C-(
2-O-tert-butyldimethylsilyl-3,6-
-ribo-3,4,5-tri-O-tert-butyl-
1
1723 cm−1; H NMR (CDCl3) see Table 1;
D
13C NMR (CDCl3): l 201.31 (C-1), 138.25,
138.21, 137.86, 128.39, 128.32, 128.09, 127.91,
127.83, 127.78, 127.66 (Ar), 81.96 (C-4), 75.01
(C-3), 74.48 (C-5), 73.95, 71.71, 70.73
(OCH2Ph), 44.62 (C-2), 15.64 (C-6); Anal.
Calcd for C27H30O4: C, 77.48; H, 7.22. Found:
C, 77.30; H, 6.86.
dimethylsilyl-3,4,5 trihydroxy-1-oxo-hexyl)- -
D
xylo-hexopyranoside (16).—Compound 13
(143 mg, 0.28 mmol) was dissolved in THP (3
mL) and treated for 30 min at 0 °C with
pyridine (0.1 mL) and (COCl2)2 (0.032 mL,
0.31 mmol). After warming to rt, the mixture
was quickly filtered on oven-dried Celite, the
filtrate was evaporated and dried under high
vacuum for 30 min. The crude acid chloride
14 was then dissolved in THP (0.5 mL) and
used immediately.
3,4,5 - Tri - O - tert - butyldimethylsilyl - 2,6-
dideoxy- -ribo-hexose (12).—A solution of 9
D
(240 mg, 0.40 mmol) in acetone (7 mL) con-
taining water (0.7 mL) was treated at rt with
HgCl2 (416 mg, 1.53 mmol) and HgO (105
mg, 0.48 mmol). After 3 h, the reaction mix-
ture was treated as described above for the
preparation of 10. Chromatography (2:1
petroleum ether–toluene) gave the product as
a clear oil (184 mg, 93%). [h]2D0 −6.5° (c 0.84,
A suspension of diiodosamarium in THP
was prepared from samarium powder (234
mg, 1.55 mmol) and 1,2-diiodoethane (292
mg, 1.04 mmol) in THP (6 mL). To this dark
blue suspension, under Ar, were added at rt
neat ketone 6 (59 mg, 0.22 mmol) and imme-
diately after, the freshly prepared solution of
acid chloride 14 in THP. After 10 min, the
dark blue mixture was vigorously stirred un-
der a stream of dry air until complete oxida-
tion of the diiodosamarium occurred (greenish
color) and then quenched with 5% NH4Cl
solution. The greenish yellow solid was
filtrated on Celite and washed thoroughly with
CH2Cl2. Work-up and chromatography (12:1
petroleum ether–EtOAc) gave 16 (105.3 mg,
63%, 8:1 mixture of diastereoisomers). Com-
pound 16 was obtained in pure form after
chromatography with 20:1 petroleum ether–
1
CHCl3); IR (liquid film): w 1731 cm−1; H
13
NMR data see Table 1; C NMR (CDCl3): l
202.76 (C-1), 81.68 (C-4), 69.81 (C-3), 69.33
(C-5), 46.32 (C-2), 26.13, 26.09, 25.88
(C(CH3)3), 20.12 (C-6); 18.37, 18.09, 17.99
(C(CH3)3), −3.82, −4.22, −4.25, −4.49,
−4.63, −4.72 (CH3Si). Anal. Calcd for
C24H54O4Si3: C, 58.71; H, 11.08. Found: C,
58.90; H, 10.94.
3,4,5 - Tri - O - tert - butyldimethylsilyl - 2,6-
dideoxy- -ribo-hexuronic acid (13).—Com-
D
pound 12 (184 mg, 0.37 mmol) was dissolved
in t-BuOH (3 mL), aq NaH2PO4 (1.7 mL of a
5% solution) was added and the mixture was
treated at rt with KMnO4 (1 mL of a 1 M
solution, 1.0 mmol). After 2 h at rt, the reac-
tion was quenched with satd Na2S2O3 solution
and diluted with CH2Cl2. Redissolution of the
brown precipitate was effected by dropwise
addition of a 3 M HCl solution before extrac-
tion with CH2Cl2. Chromatography (20:1
petroleum ether–EtOAc) gave 13 as a clear oil
(158 mg, 83%). [h]2D0 −15.7° (c 1.59, CHCl3);
1H NMR data see Table 1; 13C NMR
1
EtOAc. [h]2D0 −3° (c 0.72, CHCl3); H NMR
13
data see Table 2; C NMR (CDCl3): l 209.18
(C-1%), 99.88 (C-1), 81.84 (C-4%), 81.11 (C-4),
69.99 (C-3%), 69.13 (C-5%), 66.09 (C-2), 64.74
(C-5), 55.48 (OCH3), 39.98 (C-2%), 35.88 (C-3),
26.08, 26.06, 25.92, 25.76 (C(CH3)3), 20.67
(C-6%), 18.34, 18.13, 17.99 (2) (C(CH3)3), 14.09
(C-6), −3.83, −3.86, −4.46, −4.54,
−4.58, −4.69 (2), −4.78 (CH3Si). Anal.
Calcd for C37H80O8Si4: C, 58.06; H, 10.54.
Found: C, 57.80; H, 10.56.

246
J. Prandi / Carbohydrate Research 332 (2001) 241–247
Methyl
dideoxy-4-C-(
dimethylsilyl - 1,3,4,5 - tetrahydroxyhexyl) -
2-O-tert-butyldimethylsilyl-3,6-
26.00, 25.97, 25.87 (C(CH3)3), 19.71 (C-6%),
18.39, 18.28, 18.05 (C(CH3)3), 13.85 (C-6),
−4.06, −4.16, −4.28 (2), −4.47, −4.58,
−4.61, −4.67 (CH3Si). Anal. Calcd for
C37H82O8Si4: C, 57.91; H, 10.77. Found: C,
57.98; H, 11.11.
D
-altro-3,4,5-tri-O-tert-butyl-
D
-
xylo-hexopyranoside (17).—Compound 16
(38.1 mg, 0.05 mmol) was treated at rt with an
excess of NaBH4 in MeOH (2 mL) for 24 h.
Work-up
and
chromatography
(10:1
Methyl 2-O-acetyl-3,6-dideoxy-4-C-(
tro-1,3,4,5-tetra-O-acetyl-1,3,4,5 tetrahydroxy-
hexyl)- -xylo-hexopyranoside (18).—Com-
D
-al-
petroleum ether–EtOAc) gave starting com-
pound 16 (4.0 mg, 10%), the 1%R isomer of 17
(6.0 mg, 15%) and 17 (27.8 mg, 73%). [h]D20
D
pound 17 (26 mg, 0.034 mmol) was dissolved
in MeOH (1 mL) and treated with HCl (50 mL
of a 6 M aq solution) for 3 h at rt.
The reaction mixture was neutralized with
a basic resin, filtrated and the filtrate
evaporated. Chromatography (6:1 CH2Cl2–
1
+11.8° (c 2.27, CHCl3); H NMR data see
Table 2; 13C NMR (CDCl3): l 99.49 (C-1),
81.66 (C-4%), 74.55 (C-4), 71.74, 71.46 (C-1%,
C-3%), 69.42 (C-5%), 67.05 (C-2), 65.82 (C-5),
55.22 (OCH3), 33.94 (C-2%), 33.11 (C-3), 26.18,
Table 2
1H NMR chemical shifts (l), apparent multiplicities and coupling constants in Hz for compounds 16, 17, 2 and 18
a
H
1
16
17 a
2 b
18 c
4.59 d
4.52 d
4.68 d
4.93 d
J1,2 3.5
J1,2 3.5
J1,2 3.5
4.05 m
J2,3a 12.0
J2,3e 5.0
1.89–1.74
J1,2 3.5
2
4.13 ddd
J2,3a 11.5
J2,3e 4.5
1.50 dd
J3e,3a 12.0
2.39 m
4.04 ddd
J2,3a 11.5
J2,3e 4.5
1.58 dd
J3e,3a 12.0
1.98 m
5.15 ddd
J2,3a 12.5
J2,3e 5.0
2.05 dd
J3e,3a 12.0
2.39 m
3eq
3ax
5
2.03 m
J3a,3e 12.0
4.24 q
J5,6 6.5
1.24 d
3.82 dd
J1%,2%a 11.0
J1%,2%b 2.5
4.18 q
J5,6 6.5
0.92 d
4.09 q
J5,6 6.5
1.16 d
3.70 m
J1%,2%a 7.0
J1%,2%b 5.0
4.00 q
J5,6 6.5
1.34 d
5.35 dd
6
1%
J1%,2%a 1.5
J1%,OH 3.0
J1%,2%b 10.5
3.12 dd
J2%a,2%b 17.5
J2%a,3% 8.5
2.38 dd
J2%b,3 2.5
4.58 m
J3%,4% 2.0
2%a
1.90 ddd
J2%a,2%b 14.5
J2%a,3% 6.5
1.56 m
J2%b,3 4.0
1.89–1.74
1.89–1.74
1.89–1.74
1.89–1.74
2.09 ddd
J2%a,2%b 14.5
J2%a,3% 2.5
2.48 ddd
J2%b,3 11.5
5.37 ddd
J3%,4% 3.5
2%b
3%
4.05 m
J3%,4% 3.5
3.89 m
4%
3.48 dd
J4%,5% 6.0
3.60 m
3.61 dd
J4%,5% 6.0
3.85 m
3.49 dd
J4%,5% 6.0
3.94 m
5.53 dd
J4%,5% 6.0
5.28 m
5%
J5%,6% 6.0
1.15 d
J5%,6% 6.0
1.13 d
J5%,6% 6.0
1.31 d
J5%,6% 6.0
1.19d
6%
Other
signals
OH s 4.02
OMe s 3.46
4×t-BuSi 0.94,
0.90, 0.87, 0.83
8×MeSi 0.19–0.03
OH (C-1%) d 2.88
OH (C-4) s 2.10
OMe s 3.40
4×t-BuSi 0.90, 0.89
8×MeSi 0.16–0.07
OMe s 3.49
OMe s 3.05
OAc 5s 1.88
1.75, 1.74,
1.72, 1.70
a In CDCl3.
b In CD3OD.
c In C6D6.

J. Prandi / Carbohydrate Research 332 (2001) 241–247
247
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MeOH) gave methyl a- -caryophylloside 2
D
(8.1 mg, 77%). [h]2D0 +56° (c 0.81, MeOH); 1H
NMR data see Table 2; 13C NMR (CD3OD):
l 100.55 (C-1), 79.67 (C-4%), 75.93 (C-4), 71.64
(C-1%), 70.47 (C-3%), 69.62 (C-5%), 67.99 (C-5),
66.50 (C-2), 55.81 (OCH3), 34.14 (C-3), 32.72
(C-2%), 18.91 (C-6%), 13.75 (C-6). 2 (8.1 mg,
0.026 mmol) was dissolved in pyridine (1 mL)
and acetylated with Ac2O (0.5 mL) at 80 °C
for 30 min to give pentaacetate 18 (11.2 mg,
82%) after chromatography (1:1 petroleum
ether–EtOAc). [h]2D0 +49° (c 0.88, CHCl3); 1H
13
NMR data see Table 2; C NMR (CDCl3): l
170.43, 170.39, 170.07, 169.93 (CO), 96.21
(C-1), 74.15 (C-4), 73.59, 70.03, 68.23, 67.70,
67.51, 66.06 (C-5), 55.38 (OCH3), 29.63 (C-2%),
27.44 (C-3), 21.08, 21.03, 20.89, 20.85, 20.79
(CH3CO), 16.26 (C-6%), 13.31 (C-6). Anal.
Calcd for C23H36O13: C, 53.07; H, 6.97.
Found: C, 53.31; H, 6.87.
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