Chemoenzymatic synthesis of glycosyl-deoxyinositol derivatives. First example of a fagopyritol β-analogue containing an aminoinositol unit

Article abstract of DOI:10.1016/j.tetasy.2009.08.011

The first synthesis of two fagopyritol β-analogues (β-d-galactopyranosyl-(1′→1)-conduramine F-4 and β-d-galactopyranosyl-(1′→3)-4-aminodeoxy-l-chiro-inosito l) has been accomplished by a chemoenzymatic route in satisfactory yields. The key step of the synthesis is the TMSOTf-promoted glycosylation reaction of a deoxyconduritol derivative. The methodology is amenable to scale-up and expandable to the preparation of other pseudofagopyritols.

Full text of DOI:10.1016/j.tetasy.2009.08.011

Tetrahedron: Asymmetry 20 (2009) 2061–2064
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Chemoenzymatic synthesis of glycosyl-deoxyinositol derivatives. First
example of a fagopyritol b-analogue containing an aminoinositol unit
b
b
c
a
Ana Bellomo a, , Julia B. Bonilla , Javier López-Prados , Manuel Martín-Lomas , David Gonzalez
*
a Laboratorio de Síntesis Orgánica, Fac. de Química, Universidad de la República (UdelaR), C.C. 1157 Montevideo, Uruguay
b Centro de Investigaciones Científicas de Isla de la Cartuja, Instituto de Investigaciones Químicas (I.I.Q.), Sevilla, Spain
c Centro de Investigación Cooperativa en Biomateriales, Parque Tecnológico de San Sebastián, Edificio Empresarial ‘C’, P° Miramon 182, Guipúzcoa, Spain
a r t i c l e i n f o
a b s t r a c t
D
-galactopyranosyl-(10?1)-conduramine F-4 and b-
Article history:
Received 8 July 2009
Accepted 6 August 2009
Available online 14 September 2009
The first synthesis of two fagopyritol b-analogues (b-
D
-galactopyranosyl-(10?3)-4-aminodeoxy-
L-chiro-inositol) has been accomplished by a chemoenzymatic
route in satisfactory yields. The key step of the synthesis is the TMSOTf-promoted glycosylation reaction
of a deoxyconduritol derivative. The methodology is amenable to scale-up and expandable to the prep-
aration of other pseudofagopyritols.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
rate chirality and prepared the cis-cyclohexadienediol 2 with
complete regio- and stereoselectivity (Scheme 1). We have
Over 40 years ago, Gibson et al. reported the controlled micro-
bial oxidation of several benzene derivatives to cyclohexadienedi-
ols employing the blocked mutant Pseudomonas putida F39/D.1,2
Despite the complete stereospecificity of the reaction, little use of
this transformation had been made in organic synthesis until nearly
twenty years after with the synthesis of (+)-pinitol from benzene by
Ley et al.3 After this, the growth in applications of the arene dioxy-
genase enzymes to enantioselective synthesis has been large and it
has been the object of several reviews.4,5
To the best of our knowledge, there are no reports in the liter-
ature on the use of these bacterial metabolite derivatives as part-
ners in a glycosylation reaction to generate fagopyritol analogues.
Fagopyritols are pseudo-oligosaccharides composed of a cyclitol
unit and a sugar molecule. Particular importance is given to dimers
previously used this methodology for the preparation of inositols,7
aminoconduritols,8 and sulfur containing cyclitol analogues9,10
introducing the required functionality in the cyclohexadiene
nucleusina stereospecificfashion. Theknownepoxide311 wasavail-
able in two steps from the homochiral metabolite 2 which was sub-
jected to radical dehalogenation using SnBu3H as the hydrogen
donorand azobiscyclohexancarbonitrile (ABCC) as an initiator. Azid-
olysis of the debrominated compound gave hydroxyazide 4,12 which
was envisioned to be a useful intermediate bearing a nucleophilic
hydroxyl moiety that can operate in the glycosylation reaction.
Glycoside bond formation is often the key step in most carbohy-
drate synthesis.13 The ability of O-glycosyl trichloroacetimidates
(O-TCAs)14 to act as glycosyl donors under mild acid catalysis, usu-
ally giving a high product yield and excellent stereoselectivity,15
prompted us to choose 5 (Scheme 2) as a donor because of its accu-
rate reactivity to furnish regio- and stereoselectively the b-isomer
as the main product in the glycosylation reaction. Compound 5 was
prepared according to the established literature procedures.16
The glycosylation of acceptor 4 with donor 5 in the presence of a
catalytic amount of TMSOTf at ꢀ15 °C yielded glycoside 6 in excel-
lent yield, and no additional products were detected in the reaction
(Scheme 2). The structure of compound 6 was corroborated by
means of 2D NMR spectroscopy (COSY, HSQC) which identified
the anomeric proton (d = 4.8 ppm, J = 8.0 Hz) and confirmed the
downfield shift of the carbon bearing the glycosidic moiety. In this
case, the stereochemical outcome of the glycosylation reaction is
governed by neighboring group participation.17–20 Zemplen’s
method was applied to the deacylation of 9 giving the desired com-
pound 7 in 74% yield.
formed by D- and L-chiro-inositol with hexoses since there is evi-
dence that insulin resistance is related to a decreased D-chiro-ino-
sitol concentration in plasma in type II diabetes mellitus patients.6
Therefore, we have embraced the search for a short strategy to
prepare fagopyritol b-analogues and we report herein the first syn-
thesis of b-
D D-
-galactopyranosyl-(10?1)-conduramine F-4 and b-
galactopyranosyl-(10?3)-4-aminodeoxy-
L-chiro-inositol where the
cyclitol moiety was prepared by a chemoenzymatic route and gly-
cosylated using the trichloroacetimidate method.
2. Results and discussion
We first made use of the enzymatic catalysis by exposing bromo-
benzene to a culture of the mutant strain P. putida F39/D to incorpo-
In order to obtain the desired pseudodisaccharide, two final
steps were required: removal of the isopropylidene group and
* Corresponding author. Tel.: +5982 9244066; fax: +5982 9241906.
E-mail address: abellomo@fq.edu.uy (A. Bellomo).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.08.011

2062
A. Bellomo et al. / Tetrahedron: Asymmetry 20 (2009) 2061–2064
Br
Br
Br
O
O
O
O
OH
OH
a
b-c
d-e
N3
OH
O
1
2
3
4
Scheme 1. Chemoenzymatic preparation of the azidoconduritol derivative 4. Reagents and conditions: (a) P. putida F39/D, mineral broth, arginine, 28 °C, 48 h, 2 g/L; (b) DMP,
p-TsOH, acetone, rt, 30 min, 98%; (c) m-CPBA, CH2Cl2, rt, overnight, 85%; (d) ABCC, HBu3Sn, THF, reflux, 88%; (e) NaN3, NH4Cl, THF–EtOH–H2O, reflux, 1 h, 95%.
OAc
OAc
O
N3
N3
O
O
OAc
O
OH
OH
AcO
AcO
b
a
O
O
O
AcO
N3
O
O
HO
OTCA
O
O
OH
OAc
OAc
OH
7
4
5
6
Scheme 2. Glycosylation reaction between hydroxyazide 4 and trichloroacetimidate 5 and deacylation of 6. Reagents and conditions: (a) TMSOTf, CH2Cl2, ꢀ15 °C, 0.5 h, 92%;
(b) MeONa, MeOH, rt, 1 h, 74%.
reduction of the azide group in dimer 7. Therefore, the compound
was subjected to Dowex resin acid-catalyzed hydrolysis at room
temperature to remove the acetal, but the starting material was
recovered unchanged. At this point, we decided to warm the reac-
tion mixture initially to 40 °C and then to reflux. Unfortunately,
mild warming of the reaction was ineffective and the products ob-
tained by heating at reflux were derived from the cleavage of the
glycosidic linkage.
In light of this, we reasoned out that the desired compound
could be obtained by inverting the order of events so as to avoid
the problems which arose during hydrolysis of the cyclic acetal.
First, we exposed 6 to a Staüdinger type reduction of the azide
group and then we subjected the crude mixture to Dowex resin
catalyzed hydrolysis (Scheme 3). This last step was carried out in-
side a chromatography column loaded with Dowex resin in its
acidic form. We had previously used this protocol with very good
results in the synthesis of (ꢀ)-conduramine C-4,8 hence we
decided to test it in the one-pot synthesis of 8 from 9. We were
showed that the compound was obtained free from any residue
of the starting azide or aminoacetonide but along with variable
amounts of ammonium acetate. The contaminant did not preclude
the analysis but was observable as a sharp peak in the proton NMR.
In an attempt to synthesize a fagopyritol analogue bearing an
inositol unit, glycoside 6 was oxidized using catalytic RuCl3 and
NaIO4 as a co-oxidant. In particular, Hudlicky and Desjardins had
described the dihydroxylation of
a conduritol acetal with a
RuCl3–NaIO4 mixture in their synthesis of allo-inositol.21 RuO4 is
isoelectronic to OsO4 and several reports in the literature describe
its use as an effective and greener alternative for the dihydroxyla-
tion of unreactive alkenes.22–24 It is known that RuO4 can rapidly
cleave C,C-double bonds.25,26 However, the nucleophilic addition
of water to the intermediate ruthenate is faster in a 3:3:1 mixture
of ethyl acetate, acetonitrile and water. Any other solvent combi-
nation facilitated the scission reaction.25 As a consequence we
chose this ternary solvent mixture. Under these conditions, dihydr-
oxylation of 6 furnished syn-diol 9 with the reaction completed
within 2 h. With dihydroxylation under kinetic control being the
thrilled when this procedure gave enantiopure b-D-galactopyrano-
syl-(10?1)-6-amino-cyclohex-4-ene-2,3-diol 8 (conduramine F-4
numbering) as the only product in 80% yield for the two consecu-
tive operations (51% overall yield from 2). Spectroscopic analysis
less hindered
previously observed in our thiocyanodeoxy-
sis.9 Analysis of the spectra of compound 9 showed that the key
L-chiro-like isomer was exclusively formed as we
L-chiro-inositol synthe-
N3
H2N
OH
OH
OAc OAc
H2N
HO
OAc
O
OAc
OH
O
O
O
a
b
O
O
HO
O
O
AcO
AcO
O
O
OH
OAc
OAc
8
6
β-D-galactopyranosyl-(1',1)-
conduramine F-4
c
H2N
N3
OH
OH
OAc
OAc
OAc
O
OAc
H2N
HO
OH
O
O
O
OH
OH
O
OH
OH
d
O
OH
OH
e
HO
O
O
AcO
AcO
O
O
OH
OAc
OAc
10
9
β-D-galactopyranosyl-(1',3)-
4-aminodeoxy-L-chiro-inositol
Scheme 3. One-pot sequence for the synthesis of fagopyritol analogues 8 and 10. Reagents and conditions: (a) PPh3, THF, rt, 24 h, then H2O, rt, 4 h; (b) Dowex-resin (H+ form),
MeOH and then NH4OH 2 M, 80% (both steps); (c) RuCl3–NaIO4, AcOEt–CH3CN–H2O, 0 °C, 3 h, 91%; (d) PPh3, THF, rt, 24 h, then H2O, rt, 24 h; (e) Dowex-resin (H+ form), MeOH
and then NH4OH 2 M, 51% (both steps).

A. Bellomo et al. / Tetrahedron: Asymmetry 20 (2009) 2061–2064
2063
proton H3 is a triplet coupled with a large diaxial coupling con-
stant (J = 10.1 Hz) to the neighboring protons H2 and H4.
The same one-pot procedure applied to the synthesis of 8 was
successfully employed here giving 10 in 51% overall yield for both
steps (Scheme 3) and in 30% overall yield from metabolite 2. As for
compound 8, glycoside 10 was obtained next to variables amounts
of ammonium acetate.
O–C–O–C: isopropylidene); ESI-MS m/z: 564.0 ((M++Na), 100),
536.0 ((M++Na)ꢀN2, 21); 1H NMR (CDCl3, 400 MHz) d: 5.96 (dt,
1H, J4,3 10.0 Hz, J4,5 2.4 Hz, H-4), 5.76 (dd, 1H, J3,4 10.0 Hz, J3,2
0
0
0
0
2.7 Hz, H-3), 5.38 (dd, 1H, J4 ,3 3.4 Hz, J4 ,5 0.8 Hz, H-4’), 5.26 (dd,
0
0
0
0
0
0
0
0
1H, J2 ,1 8.1 Hz, J2 ,3 10.4 Hz, H-2’), 5.04 (dd, 1H, J3 ,4 3.5 Hz, J3 ,2
0
0
10.4 Hz, H-3’), 4.83 (d, 1H, J1 ,2 8.0 Hz, H-1’), 4.61 (m, 1H, H-5),
0
0
4.25 (dd, 1H, J6,5 6.4 Hz, J6,1 8.0 Hz, H-6), 4.15 (d, 2H, J6 ,5 6.6 Hz,
0
0
H-6’), 3.91 (d, 1H, J5 ,6 6.8 Hz, H-5’), 3.88 (br d, 1H, J2,1 8.2 Hz, H-
2), 3.69 (t, 1H, J1,6 8.0 Hz, J1,2 8.0 Hz, H-1), 2.14 (s, 3H, OAc), 2.06
(s, 3H, OAc), 2.02 (s, 3H, OAc), 1.97 (s, 3H, OAc), 1.49 (s, 3H, CH3),
1.38 (s, 3H, CH3); 13C NMR (CDCl3, 100 MHz) d: 170.2 (C (OAc)),
170.0 (C (OAc)), 169.3 (2 C (OAc)), 127.9 (C 3), 126.7 (C 4), 110.3
(C, isopropylidene), 101.0 (C 1’), 79.7 (C 1), 75.5 (C 6), 72.0 (C 5),
71.0 (C 3’), 70.9 (C 5’), 69.0 (C 2’), 67.1 (C 4’), 61.3 (C 6’), 61.0 (C
2), 27.9 (CH3, isopropylidene), 25.7 (CH3, isopropylidene), 20.6
(CH3 (OAc)), 20.5 (CH3 (OAc)), 20.5 (CH3 (OAc)), 20.4 (CH3 (OAc)).
HRMS (FAB+) m/z calcd for (C23H31N3O12Na)+: 564.1805; found:
564.1825.
3. Conclusions
In conclusion, we have completed the first synthesis of a fagopyr-
itol analogue by a chemoenzymatic route. The analogue, b-
topyranosyl-aminodeoxy- -chiro-inositol 10 is the first example
of an aminodeoxy-inositol glycoside, and in light of the known
literature on fagopyritol bioactivity it might be a potential lead for
new biomedical compounds. Furthermore, the one-pot sequence
developed for the end game of the synthesis rendered the free gly-
coside in good yield and is probably amenable for process scale-
up. Research on the biological activity of the dimers synthesized is
currently in progress and will be disclosed in forthcoming reports.
D-galac-
L
4.3. (1R,2S,5R,6R)-b-D-Galactopyranosyl-(1’?1)-2-azido-5,6-O-
isopropylidenedioxycyclohex-3-ene 7
4. Experimental
4.1. General
To a solution of 6 (16.0 mg, 0.029 mmol) in anhydrous MeOH
(3 mL), MeONa (10.0 mg, 0.185 mmol) was added under an argon
atmosphere. The reaction mixture was stirred at rt for 1 h where-
upon it was quenched with Amberlite IR-120 H+ resin. The resin
was filtered off and the solvent was removed under reduced pres-
All non-hydrolytic reactions were carried out under either a
nitrogen or argon atmosphere, with standard techniques for the
exclusion of moisture. All solvents were purified and dried prior
to use. The commercially available reagents were purchased from
Aldrich or Acros and were used without further purification. Opti-
cal rotations were measured using a Zuzi 412 automatic polarime-
ter with a 7 mL cell, a Kruss Optronic GmbH P8000 polarimeter
with a 0.5 mL cell or a Perkin–Elmer 341 polarimeter with a
1 mL cell (concentration c given as g/100 mL). Infrared spectra
were recorded using a Matheson Excalibur spectrometer and a
Vector 22 (Bruker) and peaks are reported in reciprocal centimeter
along with relative signal intensities and characteristics: s (strong);
m (medium); and w (with). Nuclear magnetic resonance spectra
were recorded on a Bruker Avance DPX-400 instrument or a
DPX-500 instrument. Chemical shifts (d) are given in parts per mil-
lion and coupling constants (J) are reported in hertz. Low-resolu-
tion mass spectra were performed on a Micromass Autospec
instrument. High-resolution mass spectra were performed on a
Bruker Daltonics model TOFQ (ESI + mode). Analytical TLC was per-
formed on Silica Gel 60F-254 plates and visualized with UV light
(254 nm) and/or anisaldehyde–H2SO4–AcOH, ninhydrin, phospho-
molybdic acid–Ce2SO4–H2SO4–H2O as detecting agent. Flash col-
umn chromatography was performed in silica gel (Kieselgel 60,
EM Reagents, 230–400 mesh or Merck 60 15–40 mesh.
sure to give 7 in 74% yield as a colorless oil. ½a D20
¼ þ11 (c 0.40,
ꢁ
MeOH); IR (film)
m
max/cmꢀ1: 3458-3284 (w, OH), 2100 (s, N3),
1065 (s, C–O–C: glycosidic linkage), 1042 (s, C–O–C–O–C: isopro-
pylidene); ESI-MS (m/z): 396 (M++Na, 100); 1H NMR (MeOD,
500 MHz) d: 5.97 (dt, 1H, J4,3 10.0 Hz, J4,5 2.0 Hz, H-4), 5.83 (dd,
1H, J3,4 10.0 Hz, J3,2 1.5 Hz, H-3), 4.69 (m, 1H, H-5), 4.58 (d, 1H,
0
0
J1 ,2 7.5 Hz, H-1’), 4.37 (t, 1H, J6,1 7.0 Hz, J6,5 7.0 Hz, H-6), 4.08 (br
dd, 1H, J2,3 1.5 Hz, J2,1 7.5 Hz, H-2), 3.89 (t, 1H, J1,2 7.5 Hz, J1,6
0
0
7.5 Hz, H-1), 3.86 (m, 1H, H-4’), 3.77 (d, 2H, J6 ,5 6.5 Hz, H-6’),
0
0
0
0
3.59–3.54 (m, 2H, H-3’ and H-5’), 3.51 (dd, J2 ,1 7.0 Hz, J2 ,3
9.5 Hz, H-2’), 1.50 (s, 3H, CH3), 1.39 (s, 3H, CH3); 13C NMR (MeOD,
125 MHz) d: 128.8 (C 3), 128.1 (C 4), 111.4 (C, isopropylidene),
104.5 (C 1’), 79.2 (C 1), 76.9 (C 6), 76.6 (C 5’), 75.1 (C 2’), 73.4 (C
5), 72.7 (C 3’), 70.3 (C 4’), 62.2 (C 6’), 61.7 (C 2), 28.3 (CH3, isopro-
pylidene), 26.1 (CH3, isopropylidene). HRMS (FAB+) m/z calcd for
(C15H23N3O8Na)+: 396.1383; found: 396.1401.
4.4. b-D-Galactopyranosyl-(1’?1)-conduramine F-4 8
Pseudodisaccharide 6 (30.6 mg, 0.057 mmol) was dissolved in
anhydrous THF (2 mL) after which PPh3 was added (53.8 mg,
0.205 mmol) under N2 atmosphere. After stirring for 24 h at rt,
water (25 equiv) was added to the system and the reaction was
stirred for other 4 h. The reaction mixture was concentrated under
vacuum and the solid obtained was taken in CH2Cl2 and applied to
a Dowex-50 (H+ form, 100 mesh) column. It was first eluted with
MeOH (to remove triphenylphosphine and triphenylphosphine
oxide) and then NH4OH 2 M (20 mL) was used. The alkaline eluate
was evaporated under reduced pressure at 30 °C to give compound
4.2. (1R,2S,5R,6R)-20,30,40,60-Tetra-O-acetyl-b-
D-galactopyranosyl-
(10?1)-2-azido-5,6-O-isopropylidenedioxycyclohex-3-ene 6
A mixture of hydroxyazide 412 (75.7 mg, 0.36 mmol) and galac-
topyranosyl-trichloroacetimidate 5 (270.8 mg, 0.55 mmol) in dry
CH2Cl2 (6.0 mL) was cooled to ꢀ15 °C and treated with a solution
8 as a syrup (80%). ½a D20
ꢁ
¼ ꢀ12 (c 0.26, H2O)*; 1H NMR (MeOD,
of TMSOTf in CH2Cl2 (9 lL, 0.1 equiv). The reaction mixture was
400 MHz) d: 5.92 (ddd, 1H, J4,5 10.0 Hz, J4,3 4.7 Hz, H-4), 5.76 (dd,
stirred for 30 min at ꢀ15 °C until consumption of the starting
materials, as monitored by TLC. The suspension was quenched
with Et3N (0.5 mL) and the solvent was evaporated under vacuum
to give a residue that was purified by flash chromatography (60/
40: hexane/ethyl acetate) to obtain pseudodisaccharide 6 as a col-
0
0
1H, J5,4 10.1 Hz, J5,6 2.0 Hz, H-5), 4.48 (d, 1H, J1 ,2 7.6 Hz, H-1’),
4.28 (t, 1H, J3,4 4.4 Hz, J3,2 4.4 Hz, H-3), 3.92 (t, 1H, J1,6 8.1 Hz, J1,2
8.1 Hz, H-1), 3.80–3.76 (m, 3H, H-2, H-6 and H-4’), 3.68–3.61 (m,
0
0
0
0
3H, H-6’ (2H) and H-5’), 3.56 (dd, 1H, J3 ,4 3.2 Hz, J3 ,2 9.9 Hz, H-
orless oil in 92% yield. ½a D20
ꢁ
¼ þ20 (c 0.84, CHCl3); IR (film) mmax
/
0
0
0
0
3’), 3.51 (dd, 1H, J2 ,1 7.6 Hz, J2 ,3 9.9 Hz, H-2’), 1.78 (s, 1H,
NH4OAc); 13C NMR (D2O, 100 MHz) d: 130.4 (C 4), 125.3 (C 5),
103.0 (C 1’), 78.5 (C 1), 75.7 (C 5’), 72.6 (C 3’), 70.7 (C 2’), 69.3 (C
cmꢀ1: 2973 and 2942 (s, C@C), 2109 (s, N3), 1756 (s, C@O (OAc)),
1097 (s, C–O–C: glycosidic linkage), 1069, 1051 and 1042 (s, C–

2064
A. Bellomo et al. / Tetrahedron: Asymmetry 20 (2009) 2061–2064
0
0
0
0
2), 68.6 (C 4’), 66.0 (C 3), 61.0 (C 6’), 52.4 (C 6); HRMS: calcd for
(C12H21NO8H)+: 308.1326; found: 308.1340.
H-1’), 3.99 (m, 1H, H-5’), 3.93 (t, 1H, J4 ,3 3.4 Hz, J4 ,5 3.4 Hz, H-
4’), 3.85–3.82 (m, 4H, H-1, H-3, H-5 and H-6), 3.69–3.63 (br s,
0
0
0
0
(*) Compound concentration was adjusted to account for the
ammonium acetate present in the solution.
3H, H-6’ (2H) and H-2), 3.59 (dd, 1H, J3 ,2 9.9 Hz, J3 ,4 3.2 Hz, H-
0
0
0
0
3’), 3.56 (dd, 1H, J2 ,1 7.5 Hz, J2 ,3 9.9 Hz, H-2’), 3.28 (t, 1H, J4,3
9.0 Hz, J4,5 9.0, H-4), 1.80 (s, NH4OAc); 13C NMR (D2O, 100 MHz)
d: 103.0 (C 1’), 80.0 (C 3), 75.7 (C 2), 72.5 (C 3’), 71.1 (C 5’), 71.0
(C 4’), 70.7 (C 2’), 69.0 (C 1), 68.5 (C 6), 67.7 (C 5), 60.9 (C 6’),
53.6 (C 4). HRMS: m/z calcd for (C12H23NO10H)+: 342.1395; found:
342.1378.
4.5. (1S,2S,3S,4R,5S,6R)-20,30,40,60-Tetra-O-acetyl-b-
D-galactopyr
anosyl-(1’?4)-3-azido-5,6-O-isopropylidenedioxycyclohexan-1,2-
diol 9
A stirred solution of 6 (40.0 mg, 0.073 mmol) in a mixture of
ethyl acetate (1.5 mL) and acetonitrile (1.5 mL) was cooled to
0 °C and treated with a mixture of RuCl3 (2.6 mg, 6%)/NaIO4
(24.4 mg, 0.114 mmol) in water (0.5 mL). After being left to stand
at 0 °C for 2 hours, Na2S2O3 (aq) 20% was added and the mixture
was filtered using a pad of silica and washed several times with
ethyl acetate. Concentration of the solution rendered a crude oily
product, which was purified over silica flash using 40:60 hexane/
ethyl acetate as the eluting solvents affording 9 as a colorless oil
(*) Compound concentration was adjusted to account for the
ammonium acetate present in the solution.
Acknowledgments
The following organizations contributed to support this work:
PEDECIBA QUIMICA and ANII (A.B. Doctoral fellowship) and CSIC
(A.B. fellowship).
The authors acknowledge Mr. Horacio Pezaroglo (FC) for record-
ing the NMR spectra and Ph.D. Alejandra Rodríguez and B.Sc. Nata-
lia Berta for performing HRMS.
in 91% yield. ½a 2D0
¼ ꢀ57 (c 0.24, CH2Cl2); IR (film): 3500 (w, OH),
ꢁ
2116 (s, N3), 1752 (s, C@O (OAc)), 1078 (s, C–O–C: glycosidic link-
age); 1H NMR (CDCl3, 400 MHz) d: 5.38 (br d, 1H, J4 ,3 3.4 Hz, H-4’),
0
0
0
0
0
0
0
0
5.25 (dd, 1H, J2 ,1 8.1 Hz, J2 ,3 10.4 Hz, H-2’), 5.03 (dd, 1H, J3 ,4
References
0
0
0
0
3.5 Hz, J3 ,2 10.4 Hz, H-3’), 4.84 (d, 1H, J1 ,2 8.1 Hz, H-1’), 4.28 (m,
0
0
3H, H-1, H-5 and H-6), 4.15 (d, 2H, J6 ,5 6.6 Hz, H-6’), 3.91 (t, 1H,
1. Gibson, D. T.; Hensley, M.; Yoshioka, H.; Mabry, J. J. Biochemistry 1970, 9, 1626.
2. Gibson, D. T.; Koch, J. R.; Kallio, R. E. Biochemistry 1968, 7, 2653.
3. Ley, S. V.; Sternfeld, F.; Taylor, S. Tetrahedron Lett. 1987, 28, 225.
4. Hudlicky, T.; Gonzalez, D.; Gibson, D. T. Aldrichim. Acta 1999, 32, 35.
5. Hudlicky, T.; Reed, J. W. Synlett 2009, 685.
6. Obendorf, R. L.; Horbowicz, M. U.S.A., 2002; Vol. 6, p 341.
7. Vitelio, C.; Bellomo, A.; Brovetto, M.; Seoane, G.; Gonzalez, D. Carbohydr. Res.
2004, 339, 1773.
8. Bellomo, A.; Giacomini, C.; Brena, B.; Seoane, G.; Gonzalez, D. Synth. Commun.
2007, 37, 3509.
9. Bellomo, A.; Camarano, S.; Rossini, C.; Gonzalez, D. Carbohydr. Res. 2009, 344,
44.
10. Bellomo, A.; Gonzalez, D. Tetrahedron Lett. 2007, 48, 3047.
11. Hudlicky, T.; Price, J. D.; Rulin, F.; Tsunoda, T. J. Am. Chem. Soc. 1990, 112, 9439.
12. Banwell, M. G.; Haddad, N.; Hudlicky, T.; Nugent, T. C.; Mackay, M. F.; Richards,
S. L. J. Chem. Soc., Perkin Trans. 1 1997, 1779.
13. Demchenko, A. V. Handbook of Chemical Glycosylation; Wiley-VCH: Weinheim,
2008.
0
0
0
0
J5 ,6 6.0 Hz, J5 ,4 6.0 Hz, H-5’), 3.72 (br d, 1H, J2,3 9.2 Hz, H-2), 3.64
(t, 1H, J3,2 10.1 Hz, J3,4 10.1 Hz, H-3), 3.55 (dd, 1H, J4,5 10.2 Hz, J4,3
10.1 Hz, H-4), 2.99 and 2.92 (br s, 2H, OH), 2.15 (s, 3H, OAc), 2.09
(s, 3H, OAc), 2.02 (s, 3H, OAc), 1.98 (s, 3H, OAc), 1.46 (s, 3H, CH3),
1.34 (s, 3H, CH3); 13C NMR (CDCl3, 100 MHz) d: 170.5 (C (OAc)),
170.5 (C (OAc)), 170.3 (C (OAc)), 169.7 (C (OAc)), 109.4 (C, isopro-
pylidene), 100.9 (C 1’), 81.9 (C 4), 76.7 (C 5), 76.5 (C 6), 71.1 (C 3’),
71.0 (C 5’), 70.5 (C 2), 69.1 (C 2’), 68.8 (C 1), 67.2 (C 4’), 64.1 (C 3),
61.4 (C 6’), 28.0 (CH3, isopropylidene), 26.0 (CH3, isopropylidene),
20.8 (CH3 (OAc)), 20.7 (2 CH3 (OAc)), 20.6 (CH3 (OAc)).
4.6. b-
D-Galactopyranosyl-(1’?3)-4-aminodeoxy-L-chiro-
inositol 10
14. Schmidt, R. R.; Michel, J. Angew. Chem., Int. Ed. Engl. 1980, 19, 731.
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2697. and references cited therein.
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19. Paulsen, H. Chem. Soc. Rev. 1984, 13, 15.
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23. Plietker, B.; Niggermann, M. Org. Biomol. Chem. 2004, 2, 2403.
24. Plietker, B.; Niggermann, M. J. Org. Chem. 2005, 70, 2402.
25. Plietker, B.; Niggermann, M. Org. Lett. 2003, 5, 3353.
26. Yang, D.; Zhang, C. J. Org. Chem. 2001, 66, 4814.
Pseudoglycoside 9 (24.0 mg, 0.041 mmol) was dissolved in dry
THF (4 mL) and PPh3 (39.0 mg, 0.149 mmol) was added under N2.
The reaction was stirred for 24 h at rt followed by addition of water
(25 equiv) and stirred for further 24 h at rt. The reaction mixture
was concentrated at reduced pressure and the white residue was
dissolved in CH2Cl2 and applied to a Dowex-50 (H+ form, 100
mesh) column, eluting first with MeOH (to remove triphenylphos-
phine and triphenylphosphine oxide) and then with 2 M NH4OH
(10 mL). The alkaline eluate was concentrated at 30 °C to afford
the amino compound 10 as a syrup in 51% yield. ½a D22
ꢁ
¼ þ12 (c
0.48, H2O)*; 1H NMR (D2O, 400 MHz) d: 4.46 (d, 1H, J1 ,2 7.6 Hz,
0
0