Study of 1-deoxy-1-(indol-3-yl)-L-sorbose, 1-deoxy-1-(indol-3-yl)-L-tagatose, and their analogs

Article abstract of DOI:10.1016/S0008-6215(02)00404-4

Alkaline degradation of the ascorbigen 2-C-[(indol-3-yl)methyl]-α-L-xylo-hex-3-ulofuranosono-1,4-lactone (1a) led to a mixture of 1-deoxy-1-(indol-3-yl)-L-sorbose (2a) and 1-deoxy-1-(indol-3-yl)-L-tagatose (3a). The mixture of diastereomeric ketoses underwent acetylation and pyranose ring opening under the action of acetic anhydride in pyridine in the presence of 4-dimethylaminopyridine (DMAP) with the formation of a mixture of (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(indol-3-yl)-L-xylo-hex-1-enitol (4a) and (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(indol-3-yl)-L-lyxo-hex-1-enitol (5a), which were separated chromatographically. Deacetylation of 4a or 5a afforded cyclised tetrols, tosylation of which in admixture resulted in 1-deoxy-1-(indol-3-yl)-3,5-di-O-tosyl-α-L-sorbopyranose (12a) and 1-deoxy-1-(indol-3-yl)-4,5-di-O-tosyl-α-L-tagatopyranose (13a). Under alkaline conditions 13a readily formed 2-hydroxy-4-hydroxymethyl-3-(indol-3-yl)cyclopenten-2-one (15a) in 90% yield. Similar transformations were performed for N-methyl- and N-methoxyindole derivatives.

Full text of DOI:10.1016/S0008-6215(02)00404-4

Carbohydrate Research 338 (2003) 143–152
www.elsevier.com/locate/carres
Study of 1-deoxy-1-(indol-3-yl)-
L-sorbose,
1-deoxy-1-(indol-3-yl)- -tagatose, and their analogs
L
Sergey N. Lavrenov,a Alexander M. Korolev,a Marina I. Reznikova,a
Andrey V. Sosnov,b Maria N. Preobrazhenskayaa,*
aGause Institute of New Antibiotics, Russian Academy of Medical Sciences, B. Pirogo6skaya 11, Moscow 119992, Russia
bState Research Institute of Organic Chemistry and Technology, Shosse Entusiasto6 23, Moscow 111024, Russia
Received 17 May 2002; accepted 30 September 2002
Abstract
Alkaline degradation of the ascorbigen 2-C-[(indol-3-yl)methyl]-a-
of 1-deoxy-1-(indol-3-yl)- -sorbose (2a) and 1-deoxy-1-(indol-3-yl)-
went acetylation and pyranose ring opening under the action of acetic anhydride in pyridine in the presence of 4-dimethy-
laminopyridine (DMAP) with the formation of mixture of (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(indol-3-yl)-
xylo-hex-1-enitol (4a) and (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(indol-3-yl)- -lyxo-hex-1-enitol (5a), which were separated
chromatographically. Deacetylation of 4a or 5a afforded cyclised tetrols, tosylation of which in admixture resulted in 1-deoxy-1-
(indol-3-yl)-3,5-di-O-tosyl-a- -sorbopyranose (12a) and 1-deoxy-1-(indol-3-yl)-4,5-di-O-tosyl-a- -tagatopyranose (13a). Under
L
-xylo-hex-3-ulofuranosono-1,4-lactone (1a) led to a mixture
L
L-tagatose (3a). The mixture of diastereomeric ketoses under-
a
L-
L
L
L
alkaline conditions 13a readily formed 2-hydroxy-4-hydroxymethyl-3-(indol-3-yl)cyclopenten-2-one (15a) in 90% yield. Similar
transformations were performed for N-methyl- and N-methoxyindole derivatives. © 2002 Elsevier Science Ltd. All rights reserved.
Keywords: Ascorbigen; Indolylketoses; Sorbose; Tagatose; Polyols
1. Introduction
the study of the products of ascorbigen transformation
in 6i6o is important. Neoascorbigen, namely 2-C-[(1-
1-Heteroaryl-containing 1-deoxyketopyranoses occur as
subunits in a number of cytotoxic polyketide natural
compounds. Synthetic access to such subunits is based
on laborious multistep syntheses.1–3 In contrast, the
methoxyindol-3-yl)methyl]-a-L-xylo-hex-3-ulofurano-
sono-1,4-lactone6 (1c) is also a component of human
and animal diet,6 and the study of products of neascor-
bigen degradation is important. However, the individ-
ual products of alkaline degradation of ascorbigens
have not until now been investigated.
diastereomeric 1-deoxy-1-(indol-3-yl)-a-
ose (2a) and 1-deoxy-1-(indol-3-yl)-a- -tagatopyranose
(3a) are readily obtainable by degradation of the ascor-
bigen 2-C-[(indol-3-yl)methyl]-a- -xylo-hex-3-ulofura-
L-sorbopyran-
L
L
nosono-1,4-lactone (1a) through a sequential domino
reaction including hydrolysis, decarboxylation, and iso-
merization.4 These ketoses are also of interest as they
are formed in the blood and tissues of animals which
obtained ascorbigen orally.5 As ascorbigen is the most
abundant indole-derived ingredient of cruciferous veg-
etables, which human and animals obtain with food,
2. Results and discussion
The goal of this project was the investigation of ac-
ylated derivatives of 1-deoxy-1-indolyl ketoses and the
elaboration of methods for obtaining the individual
1-deoxy-1-(indol-3-yl)- -sorbose (2a) and -L-tagatose
L
(3a). These compounds and their N-methyl analogs 2b
and 3b were obtained from ascorbigen (1a) or N-
methylascorbigen (1b) as mixtures of diastereomers.4
Alkaline degradation of neoascorbigen (1c) under the
conditions described for ascorbigen (Et3N, MeOH,
* Corresponding author
E-mail address: lcta@space.ru (M.N. Preobrazhenskaya).
0008-6215/03/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(02)00404-4

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S.N. La6reno6 et al. / Carbohydrate Research 338 (2003) 143–152
60 °C) failed.6 We obtained in 56% net yield a mixture
of 1-deoxy-1-(1-methoxyindol-3-yl)-a- -sorbopyranose
(2c) and 1-deoxy-1-(1-methoxyindol-3-yl)-a- -tagatopy-
and chromatographic separation, the individual 1-
methoxyindolyl derivatives (4c) (30%) and (5c) (20%).
Acetylation of the N-unsubstituted indolylketoses 2a+
3a led to a more-complex mixture of N-unsubstituted
penta-O-acetyl and hexa-N,O-acetyl derivatives. The
individual (E)-2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(in-
L
L
ranose (3c) under milder conditions by the degradation
of 1c in potassium phosphate buffer at pH 7.4 (Scheme
1). HPLC analysis of the crude reaction mixture
1
demonstrated the presence of two compounds. The H
dol-3-yl)-
L-xylo-hex-1-enitol (4b) (10%), (E)-2,3,4,5,6-
NMR spectrum also showed the presence of two com-
penta-O-acetyl-1-deoxy-1-(indol-3-yl)-
L
-lyxo-hex-1-
ponents having parameters close to those of a 2a+3a
enitol (5b) (13%), and the N-acetyl derivative 4d (4%)
were isolated by column chromatography followed by
crystallization. In the 1H NMR spectra of compounds 4
and 5 the H-1 singlet at 6.5–6.8 ppm and the H-3
doublet at the 5.5–5.8 ppm are diagnostic (Table 1).
The E-geometry of the double bond was shown by
NOE difference experiments. In compounds 4a,b,c,d
and 5a,b,c irradiation of the H-3 doublet led to the
enhancement of the H-1 singlet by 12–14%, it demon-
strating the trans-orientation of the indole ring and the
acetylated polyol moiety. The structures of compounds
4a,b,c,d and 5a,b,c were also supported by HRMS
spectra.
4
mixture.
The mixture was characterized by mass
spectroscopy and used for further investigation without
additional purification.
Reaction of the 2b and 3b mixture with Ac2O in
pyridine in the presence of DMAP at room temperature
for 12 h resulted in per-O-acetylation, opening of the
pyranose ring, and formation of a mixture of (E)-
2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(1-methylindol-3-yl)-
L-xylo-hex-1-enitol (4b) and (E)-penta-O-acetyl-1-de-
oxy-1-(1-methylindol-3-yl)-2,3,4,5,6- -lyxo-hex-1-enitol
L
(5b) in 58% net yield (Scheme 2). The compounds were
separated by column chromatography followed by crys-
tallization to give the individual 4b (40%) and 5b (18%).
Similarly, a mixture of the products of neoascorbigen
degradation 2c and 3c produced, after peracetylation
Acetylation of the 2b+3b mixture by the same
reagents for 1 h produced another complex mixture of
compounds, which were separated by column chro-
Scheme 1.
Scheme 2.

S.N. La6reno6 et al. / Carbohydrate Research 338 (2003) 143–152
145

146
S.N. La6reno6 et al. / Carbohydrate Research 338 (2003) 143–152
Scheme 3.
very sensitive to the solvent and temperature, for exam-
ple in the presence of CF3CO2D at 37 °C the content of
matography to give partially O-acetylated ketopyran-
oses 3,4,5-tri-O-acetyl-1-deoxy-1-(1-methylindol-3-yl)-
a-L-pyranose form was about 50%. These deacetylated
a-
deoxy-1-(1-methylindol-3-yl)-a-
(12%), and also an open-chain keto derivative, 3,4,5,6-
tetra-O-acetyl-1-deoxy-1-(1-methylindol-3-yl)- -sorbose
(8b) (21%). An individual open-chain tagatose deriva-
tive failed to be isolated (Scheme 3).
L
-sorbopyranose (6b) (14%), 3,4,5-tri-O-acetyl-1-
compounds showed one peak in HPLC; the acetylation
quantitatively produced the individual 5b. Deacetyla-
tion of 4a or 5a led to the individual components 2a
and 3a; the latter was also in equilibrium with other
tautomers (Scheme 5). These results demonstrate that
L-tagatopyranose (7b)
L
1-deoxy-(1-indol-3-yl)-a-L-tagatopyranose is conforma-
tionally unstable due to the presence of two neighbor-
ing axial hydroxyl groups, resulting in an equilibrium
between the a-L-pyranose and some other isomeric
form (open or cyclic or both) in solution.
It is note worthy that tetra-O-acetates of ketopyran-
ose forms were not isolated. The structures of com-
1
pounds 6b, 7b, and 8b were supported by H NMR
1
data. In the H NMR spectrum of compound 6b the
values of J3,4 and J4,5 correspond to trans-diaxially
Persilylation of 2b led to a tetra-trimethylsilyl com-
pound, whereas 3b under the same conditions gave a
penta–trimethylsilyl derivative; similarly 2a gave penta-
and 3a hexa-trimethylsilyl derivatives, allowing attribu-
tion of the structure 9a,b to the sorbose and 10a,b to
the tagatose persilylated derivatives respectively (MS-
data) (Scheme 4). This demonstrates facile opening of
the tagatopyranose ring or the presence of open-chain
forms in compounds 3a and 3b, in contrast to sorbopy-
ranose derivatives 2a and 2b.
Deacetylation of compounds 4 and 5 was always
accompanied by the formation of 3-formylindoles (11),
which were the predominant reaction products at tem-
peratures above over 40 °C. The formation of 3-
formylindoles can be explained by oxidative radical
degradation at the double bond7 (Scheme 5).
disposed H-3 and H-4, showing the
L-sorbopyranose
configuration and the C2 conformation. The value of
5
J3,4 (3.4 Hz) in the spectrum of 7b demonstrates the
axial-equatorial disposition of these atoms and the L-
tagatopyranose configuration. The acyclic structure of
8b was assigned on the basis of its 13C NMR spectrum,
in which the signal of the 2-CO group at 200.96 ppm is
present (Table 2). Deacetylation of this compound led
to 2b, supporting the L-sorbose stereochemistry.
Various deacetylation reagents for the individual per-
O-acetyl ketoses 4 and 5 were studied. Deacetylation of
4b or 5b with the use of MeONa or K2CO3 in methanol
was accompanied by the epimerization at C-3 leading
to a mixture of diastereomers 2b and 3b; in the mixture
obtained from 4b the sorbose derivative 2b predomi-
nated, and in the mixture obtained from 5b the tagatose
structure 3b was predominant. The structures of the
products of deacetylation were studied by HPLC and
NMR methods. Use of milder agents such as Na2CO3
or Et3N in methanol afforded the individual ketose 2b
Tosylation of the 2b+3b mixture by tosyl chloride in
pyridine under argon produced a complex mixture from
which mixtures of 1-deoxy-1-(1-methylindol-3-yl)-(3,5-
di-O-tosyl)-a-
L
-sorbopyranose (12b) and 1-deoxy-1-(1-
methylindol-3-yl)-4,5-di-O-tosyl-a-
L
-tagatopyranose
1
from 4b. The H NMR parameters of the isolated 2b
(13b) were isolated in 35–40% net yield by column
chromatography. These compounds were then sepa-
rated by preparative HPLC. Similar tosylation of the
2a+3a mixture followed by column chromatography
and then by preparative HPLC gave the individual 12a
and 13a. Chemical shifts of carbohydrate hydrogen
atoms of compounds 12b and 13b were compared with
those of the corresponding starting ketoses 2b and 3b
were identical to those described for 2b when it was
earlier4 studied in admixture with 3b. Under these
conditions compound 5b, produced a mixture of tau-
1
tomeric (3b) forms. The H NMR spectrum showed the
presence of the a-
other isomers, which were not identified. The ratio
between the a- -pyranose and the other isomers was
L-pyranose (ꢀ70%), and ꢀ30% of
L

S.N. La6reno6 et al. / Carbohydrate Research 338 (2003) 143–152
147

148
S.N. La6reno6 et al. / Carbohydrate Research 338 (2003) 143–152
(Table 1). The signals of hydrogen atoms connected
with the same carbon atom as the O-sulfonyl group are
shifted downfield (Dꢀ1 ppm) in comparison with the
corresponding nonsulfonylated compound. This com-
parison allowed the conclusion that, in the sorbopyran-
ose derivatives 12b, the hydroxyl groups at the
positions 3 and 5 are tosylated, whereas in the
tagatopyranose derivatives 13b the tosyl moieties are in
positions 4 and 5. The structures of 12a and 13a were
ascribed by analogy. The difference in reactivities be-
tween hydroxyl groups can be correlated with the dif-
ference in the orientation of 3-OH group in these two
series (eq.OH in 12 and ax.OH in 13). In methanolic
NaOH solution, compound 13a underwent decomposi-
tion with the formation of 2-hydroxy-4-hydroxymethyl-
3-(indol-3-yl)cyclopent-2-enone (15a) in 90% yield,
identical with the compound previously obtained by the
acidic degradation of ascorbigen8. Similarly 13b pro-
duces 15b in 95% yield. Earlier we have demonstrated
that the transformation of ascorbigen into 15a proceeds
via the dienone 14 with the cis-orientation of the indole
and hydroxyl groups.8 A similar transformation is de-
scribed for the 4,5-ditosylate of 1-deoxy-1-propy-
lamino-b-D-fructopyranose which forms under neutral
or basic conditions 2-hydroxy-4-hydroxymethyl-3-
propylamino-cyclopent-2-enone, a compound having a
framework similar to that of 15.9 The formation of the
intermediate dienone 14 from 3,5-ditosylate 12 is not
possible and, in contrast to the ditosyl tagatose deriva-
tives 13, the ditosyl derivatives of sorbopyranose 12
form intractable mixtures of unidentified compounds,
among which cyclopentenone derivatives 15 were not
identified (Scheme 6). This is in accordance with the
mechanism proposed.
Catalytic hydrogenation of 4b over 5% Pd/C at 1 atm
yielded in 90% yield an individual penta-O-acetyl-1-de-
Scheme 4.
Scheme 5.

S.N. La6reno6 et al. / Carbohydrate Research 338 (2003) 143–152
149
Scheme 6.
oxy-1-(1-methylindol-3-yl)-hexitol, with either the
L
-
CH3OH). Analytical HPLC analyses were performed
on a Millichrom 5 instrument (Russia), on a Diasorb C
16 column (2×120 mm and particle size 7 mm), injec-
tion volume 5 mL at 280 nm, by isocratic elution, using
systems of solvents: no. 1 (80:20 0.01 M H3PO4–
CH3CN) and no. 2 (30:70 H2O–CH3CN). Preparative
HPLC was performed on a Shimadzu HPLC series LC
10 instrument on a Diasorb C 16 column (15×250 mm
and particle size 7 mm), with injection volume 50 mL, at
280 nm, using systems of solvents: no. 3 (40:60 H2O–
CH3CN) and no. 4 (30:70 H2O–CH3CN). Melting
points were determined on a Bu¨chi SMP-20 apparatus
and are uncorrected. Silylation of compounds 2a,b and
3a,d was performed using solution of BSA in pyridine
ido- or -gulo-configuration (16) (Scheme 7). The
L
configuration of the C-2 asymmetric center of 16 re-
mains to be elucidated. Compound 16 is an acetylated
analog of 4-(indol-3-yl)butane-1,2,3-triol, a toxic indole
alkaloids, produced by a fungus Balancia epichloe¨
(Weese) which parasitizes pasture grasses and is in-
volved with ergot-type syndromes observed in cattle
grazed on infected pastures.10
3. Experimental
3.1. General methods
6
(Pierce). Neoascorbigen and mixtures of 2a+3a4 and
4
2b+3b were obtained as earlier described.
NMR spectra were recorded on a Varian VXR-400
instrument operated at 400 MHz (1H NMR) or at 100.6
MHz (13C NMR), using solvents as internal standards.
Optical rotations were measured on a Perkin–Elmer
241 polarimeter. High resolution mass spectra were
registered on a MAT 8430 Finnigan instrument (USA)
with data operating system SS-300 (EI, 70eV, direct
introduction, temperature of ion source 250 °C). Elec-
tron impact (EI) and FAB spectra were registered on a
SSQ 710 Finnigan MAT instrument (USA), (EI: 70eV,
direct introduction, FAB: reactant gas xenon, glycerol
matrix). Analytical TLC was performed on Kieselgel
F254 plates (E.Merck), preparative TLC chromatogra-
phy on plates (20×20 cm, 0.5 mm) with Kieselgel 60
F254 (E.Merck), and column chromatography on
Kieselgel 60 (E.Merck), using the following systems of
solvents: A (3:2 petroleum ether–EtOAc), B (2:1
petroleum ether–EtOAc), C (5:1 CHCl3–CH3OH), D
3.2. 1-Deoxy-1-(1-methoxyindol-3-yl)-a-L-sorbopyranose
(2c) and 1-deoxy-1-(1-methoxyindol-3-yl)-a-L-tagatopy-
ranose (3c)
A solution of neoascorbigen 1c (2.3 g, 6.9 mmol) in
potassium phosphate buffer (100 mL, pH 7.4) was
(1:1 petroleum ether–EtOAc),
E
(10:1 CHCl3–
Scheme 7.

150
S.N. La6reno6 et al. / Carbohydrate Research 338 (2003) 143–152
incubated at 40 °C for 4 h, then the solution was
saturated with NaCl, extracted with EtOAc (3×50
mL), dried (Na2SO4) and evaporated in vacuo to give
the mixture of 2c and 3c (1.2 g, 56%) as AN amorphous
powder, Rf 0.48 (C); Rt: 25.02 min (2c) and 22.35 min
(3c) (system no. 1); HR-MS, m/z: Found 309.1218,
Calcd for C15H19NO6 309.1212.
3.5. (E)-2,3,4,5,6-Penta-O-acetyl-1-deoxy-1-(indol-3-yl)-
-xylo-hex-1-enitol (4a), (E)-2,3,4,5,6-penta-O-acetyl-1-
deoxy-1-(indol-3-yl)- -lyxo-hex-1-enitol (5a), and
(E)-1-(1-acetylindol-3-yl)-2,3,4,5,6-penta-O-acetyl-1-
deoxy- -xylo-hex-1-enitol (4d)
L
L
L
(E)-2,3,4,5,6-Penta-O-acetyl-1-deoxy-1-(indol-3-yl)-
xylo-hex-1-enitol (4a), (E)-2,3,4,5,6-penta-O-acetyl-1-
deoxy-1-(indol-3-yl)- -lyxo-hex-1-enitol (5a), and (E)-1-
(1-acetylindol-3-yl)-2,3,4,5,6-penta-O-acetyl-1-deoxy-
L-
3.3. (E)-2,3,4,5,6-Penta-O-acetyl-1-deoxy-1-(1-methylin-
L
dol-3-yl)-
L-xylo-hex-1-enitol (4b) and (E)-2,3,4,5,6-
L-
penta-O-acetyl-1-deoxy-1-(1-methylindol-3-yl)-
hex-1-enitol (5b)
L
-lyxo-
xylo-hex-1-enitol (4d) were obtained by the same proce-
dure as 4b and 5b, using a mixture of 2a and 3a (1.3 g,
4.66 mmol), DMAP (60 mg), pyridine (20 mL) and
Ac2O (2.64 mL, 27.96 mmol). After extraction and
evaporation, a mixture of 4a, 4d, 5a (1.8 g) was ob-
tained, which gave after column chromatography (A)
followed by crystallization from diethyl ether the indi-
vidual 4a (225 mg, 10%), 5a (300 mg, 13%,) and 4d (250
mg, 11%).
Compound 4a: White crystals, mp 164–166 °C
(Et2O); [h]2D0 −101° (c 0.5, CHCl3); Rf 0.26 (D); HR-
MS, m/z: Found 489.1630, Calcd for C24H27NO10
489.1634.
A solution of mixed 2b and 3b (1.3 g, 4.44 mmol) and
DMAP (60 mg) in dry pyridine (20 mL) was cooled to
−10 °C, and then Ac2O (2.52 mL, 26.64 mmol) was
added. The mixture was kept at rt. for 12 h and then it
was dissolved in 1N HCl (300 mL), and extracted with
diethyl ether (3×50 mL). The extract was washed with
brine, dried (Na2SO4), and evaporated in vacuo to give
a mixture (1.8 g, 81%) of 4b and 5b as light-brown
crystals. It was chromatographed on silica gel (A), the
fractions were evaporated, and after crystallizing from
diethyl ether gave the individual 4b (0.9 g, 40%) and 5b
(0.4 g, 18%).
Compound 4b: White crystals, mp 161–163 °C
(Et2O); [h]2D0 −111° (c 0.5, CHCl3); Rf 0.40 (D); Anal.
Calcd for C25H29NO10: C, 59.62; H, 5.81; N, 2.78.
Found: C, 59.56; H, 5.78; N, 2.74.
Compound 5b: White crystals, mp 133–135 °C
(Et2O); [h]2D0 +24.6° (c 0.5, CHCl3); Rf 0.46 (D); Anal.
Calcd for C25H29NO10: C, 59.62; H, 5.81; N, 2.78.
Found: C, 59.61; H, 5.89; N, 2.66.
Compound 5a: White crystals, mp 125–127 °C
(Et2O); [h]2D0 +23° (c 0.5, CHCl3); Rf 0.39 (D) Anal.
Calcd for C24H27NO10: C, 58.88; H, 5.56; N, 2.86.
Found: C, 58.85; H, 5.48; N, 2.76.
Compound 4d: Yellow syrup; [h]2D0 −60° (c 0.5,
CHCl3); Rf 0.33 (D); HR-MS, m/z: Found 531.1737,
Calcd for C26H29NO11 531.1741.
3.6. (3,4,5-Tri-O-acetyl)-1-deoxy-1-(1-methylindol-3-yl)-
a-
(1-methylindol-3-yl)-a-
(3,4,5,6-tetra-O-acetyl)-1-deoxy-1-(1-methylindol-3-yl)-
-sorbose (8b)
L-sorbopyranose (6b), (3,4,5-tri-O-acetyl)-1-deoxy-1-
L-tagatopyranose (7b) and
3.4. (E)-2,3,4,5,6-Penta-O-acetyl-1-deoxy-1-(1-
methoxyindol-3-yl)-
2,3,4,5,6-penta-O-acetyl-1-deoxy-1-(1-methoxylindol-3-
yl)- -lyxo-hex-1-enitol (5c)
L-xylo-hex-1-enitol (4c) and (E)-
L
L
A solution of 2b and 3b mixture (300 mg, 1.02 mmol)
and DMAP (10 mg) in dry pyridine (8 mL) was cooled
to −20 °C, and then Ac2O (0.58 mL, 6.12 mmol) was
added, and the mixture was incubated at −20 °C for
20 min, stirred at rt. for 40 min, dissolved in 1 M HCl
(100 mL), and extracted with EtOAc (3×25 mL). The
extract was washed with brine, dried (Na2SO4) and
evaporated in vacuo to give a mixture of 6b, 7b and 8b
as a light brown oil. It was chromatographed on silica
gel (A), the fractions were evaporated to give the
individual products:
Compound 6b: 50 mg, 12%; white crystals, mp 134–
136 °C (Et2O); Rf 0.38 (B); [h]2D0 +33.6° (c 0.5, CHCl3);
Anal. Calcd for C21H25NO8: C, 60.14; H, 6.01; N, 3.34.
Found: C, 60.02; H, 6.02; N, 3.09.
Compound 7b: 60 mg, 14%; white crystals, mp 176–
178 °C (CHCl3); Rf 0.30 (B); [h]2D0 −12.8° (c 0.5,
CHCl3); Anal. Calcd for C21H25NO8: C, 60.14; H, 6.01;
N, 3.34. Found: C, 59.95; H, 5.96; N, 3.21.
(E)-2,3,4,5,6-Penta-O-acetyl-1-deoxy-1-(1-methoxyin-
dol-3-yl)- -xylo-hex-1-enitol (4c) and (E)-2,3,4,5,6-
penta-O-acetyl-1-deoxy-1-(1-methoxylindol-3-yl)-
L
L-
lyxo-hex-1-enitol (5c) were obtained by the same proce-
dure as 4b and 5b, starting from the mixture of 2c and
3c (150 mg, 0.49 mmol), DMAP (5 mg), pyridine (6
mL) and Ac2O (0.3 mL). After extraction, and evapora-
tion a mixture of 4c and 5c (200 mg, 79%) was ob-
tained, which gave after column chromatography (A)
followed by crystallization from diethyl ether the indi-
vidual 4c (60 mg, 30%) and 5c (40 mg, 20%).
Compound 4c: White crystals; mp 129–131 °C
(Et2O); [h]2D0 −95° (c 0.5, CHCl3); Rf 0.26 (B); HR-MS,
m/z: Found 519.1735, Calcd for C25H29NO11 519.1740.
Compound 5c: White crystals; mp 133–135 °C
(Et2O); [h]2D0 +20° (c 0.5, CHCl3); Rf 0.33 (B); HR-MS,
m/z: Found 519.1736, Calcd for C25H29NO11 519.1740.

S.N. La6reno6 et al. / Carbohydrate Research 338 (2003) 143–152
151
Compound 8b: 100 mg, 21%; yellow syrup, Rf 0.34
(B). HR-MS, m/z: Found 461.1683, Calcd for
C23H27NO9 461.1686.
[C32H65NO5Si6 (M)]+; 639 (63%) [M−(SiMe3)]+; 73
(100%) [SiMe3]+
HR-MS, m/z: Found 279.1096, Calcd for C14H17NO5
279.1107.
3-Formylindole (11a) also was isolated (3%).
3.7. 1-Deoxy-1-(1-methylindol-3-yl)-a-L-sorbopyranose
(2b)
3.11. 1-Deoxy-1-(1-methylindol-3-yl)-(3,5-di-O-tosyl)-a-
L
-sorbopyranose (12b) and 1-deoxy-1-(1-methylindol-3-
To a solution of 4b (100 mg, 0.2 mmol) in MeOH (5
mL) was added dry Na2CO3 (20 mg), and the mixture
was incubated at rt. for 3 h. The Na2CO3 was filtered
off, and the filtrate was evaporated in vacuo. The
residue was chromatographed by preparative TLC (C)
to give 2b a as white amorphous powder (40 mg, 70%);
[h]2D0 −18° (c 0.5 MeOH); Rf 0.42 (C); Rt 22.49 min
(system 1); FAB-MS of per-silylated 2b, m/z: 581 (90%)
[C27H51NO5Si4 (M)]+; 437 (21%) [M−(SiMe3)2]+; 365
(14%) [M−(SiMe3)3]+; 73 (100%) [SiMe3]+.
yl)-(4,5-di-O-tosyl)-a- -tagatopyranose (13b)
L
To a solution of 2b and 3b mixture (500 mg, 1.7 mmol)
under argon in dry pyridine (30 mL),with 3A molecular
,
sieves added, was added dropwise a solution of TsCl
(1.13 g, 5.95 mmol) in dry pyridine (5 mL) and the
mixture was stirred at rt for 7 h. The mixture was
diluted with diethyl ether (70 mL), washed with 3% aq.
NaHSO4 several times, then by brine, dried (Na2SO4),
and evaporated in vacuo. After column chromatogra-
phy (A), an inseparable mixture of 12b and 13b was
obtained (410 mg, 40%) as a yellow syrup, Rf 0.43 (A).
Individual components 12b and 13b were isolated by
preparative HPLC (the sample concentration was 200
mg/mL in CH3CN, system 4, flow rate 3.0 mL/min, Rt
33.88 and 26.07 min respectively).
Anal. Calcd for C15H19NO5: C, 61.42; H, 6.53; N,
4.78. Found: C, 61.29; H, 6.52; N, 4.75.
1-Methyl-3-formylindole (11b, 6 mg, 4%), Rf 0.80 (E)
identical with the authentic sample was also isolated.
3.8. 1-Deoxy-1-(1-methylindol-3-yl)-
L-tagatose (3b)
Compound 12b: [h]D20 −42° (c 0.42, CHCl3; Rt 12.55
min (anal. HPLC, system no. 2); FAB-MS m/z: 602
(44%) [M+H]+; 584 (100%) [M−H2O]+; 430 (52%)
[M−TosOH]+. Anal. Calcd for C29H31NO9S2: C,
57.89; H, 5.19; N, 2.33. Found: C, 57.78; H, 5.25; N,
2.20.
1-Deoxy-1-(1-methylindol-3-yl)- -tagatose (3b) was ob-
L
tained similarly from 5b (100 mg, 0.2 mmol) as a white
amorphous powder (37 mg, 65%); [h]2D0 +7.9° (c 0.7
MeOH); Rf 0.42 (C); Rt 17.78 min (system 1); FAB-MS
of per-silylated 3b, m/z: 653 (80%) [C30H59NO5Si5
(M)]+; 581 (47%) [M−SiMe3)]+; 437 (5%) [M−
(SiMe3)3]+; 73 (100%) [SiMe3]+; HR-MS, m/z: Found
293.1260, Calcd for C15H19NO5 293.1263.
Compound 13b: [h]D20 +24.1° (c 0.6, CHCl3); Rt 9.70
min (anal. HPLC, system no. 2); FAB-MS m/z: 602
(70%) [M+H]+; 584 (100%) [M−H2O]+; 430 (17%)
[M−TosOH]+. Anal. Calcd for C29H31NO9S2: C,
57.89; H, 5.19; N, 2.33. Found: C, 57.81; H, 5.28; N,
2.29.
1-Methyl-3-formylindole (11b, (4.5 mg, 3%) was also
isolated.
3.9. 1-Deoxy-1-(indol-3-yl)-a-
L-sorbopyranose (2a)
3.12. 1-Deoxy-1-(indol-3-yl)-(3,5-di-O-tosyl)-a-
sorbopyranose (12a) and 1-deoxy-1-(indol-3-yl)-(4,5-di-
O-tosyl)-a- -tagatopyranose (13a)
L-
1-Deoxy-1-(indol-3-yl)-a- -sorbopyranose (2a) was ob-
L
L
tained similarly from 4a in 67% yield as white amor-
phous powder, [h]2D0 −7.5° (c 0.8 MeOH); Rf 0.29 (C);
Rt 9.02 min (system 1); FAB-MS of silylated 2a, m/z:
639 (58%) [C29H57NO5Si5 (M)]+; 567 (12%) [M−
(SiMe3)]+; 495 (2%) [M−(SiMe3)2]+; 73 (100%)
[SiMe3]+
1-Deoxy-1-(indol-3-yl)-(3,5-di-O-tosyl)-a-
ose (12a) and 1-deoxy-1-(indol-3-yl)-(4,5-di-O-tosyl)-a-
-tagatopyranose (13a) were obtained from a mixture
L-sorbopyran-
L
of 2a and 3a (500 mg) and separated similarly, the
inseparable mixture of 12a and 13a (370 mg, 35%) was
obtained by the column chromatography as a yellow
syrup Rf 0.21 (A). The individual 12a and 13a were
separated by preparative HPLC (the sample concentra-
tion was 300 mg/mL in CH3CN, system no. 3, flow rate
2.0 mL/min, Rt 45.91 and 37.52 min respectively).
Compound 12a: White amorphous powder. [h]D20
−57.5° (c 0.2, CHCl3); Rt 7.62 min (anal. HPLC,
system no. 2); FAB-MS, m/z: 588 (20%) [MH]+; 570
(100%) [M−OH]+; 416 (68%) [M−TosOH]+. Anal.
Calcd for C28H29NO9S2: C, 57.23; H, 4.97; N, 2.38.
Found: C, 57.15; H, 4.99; N, 2.24.
Anal. Calcd for C14H17NO5: C, 60.20; H, 6.13; N,
5.06. Found C, 60.10; H, 6.05; N, 4.90.
3-Formylindole (11a, 4%) identical with an authentic
sample, was also isolated, Rf 0.44 (E).
3.10. 1-Deoxy-1-(indol-3-yl)-
L-tagatose (3a)
1-Deoxy-1-(indol-3-yl)- -tagatose (3a) was obtained
L
similarly from 5a as a white amorphous powder (61%),
[h]2D0 +8° (c 0.5 MeOH); Rf 0.29 (C); Rt 7.95 min
(system 1); FAB-MS of silylated 3a, m/z: 711 (62%)

152
S.N. La6reno6 et al. / Carbohydrate Research 338 (2003) 143–152
Compound 13a: White amorphous powder. [h]D20
+
was evaporated in vacuo. Preparative TLC (B) led to
15.3° (c 0.5, CHCl3); Rt 6.16 min (anal. HPLC, system
no. 2); FAB-MS, m/z: 588 (20%) [MH]+; 570 (100%)
[M−OH]+; 416 (60%) [M−TosOH]+. Anal. Calcd for
C28H29NO9S2: C, 57.23; H, 4.97; N, 2.38. Found: C,
57.19; H, 5.03; N, 2.29.
16b (90 mg, 90%) as white crystals, mp 96–99 °C (from
CHCl3); [h]2D0 −9.2° (c 0.5, CHCl3); Rf 0.53 (D); HR-
MS, m/z: Found 505.1941, Calcd for C25H31NO10
505.1948.
3.13. 2-Hydroxy-4-hydroxymethyl-3-(indol-3-
yl)cyclopenten-2-on (15a)
Acknowledgements
This work was supported by the Russian Fund for
Basic Research, grant number 01-03-33028 and Interna-
tional Science Technology Center, grant number 1910.
To a solution of 13a (20 mg, 0.034 mmol) in MeOH (5
mL) was added under argon degassed 10% aq. NaOH
(1 mL), and then the mixture was stirred at rt for 0.5 h,
diluted with brine (30 mL), extracted by EtOAc (2×10
mL), and the extract was evaporated in vacuo to give,
after TLC (E) 15a (7.5 mg, 90%) as a yellow amor-
phous powder identical with the authentic sample by
References
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HPLC and H NMR data.8 Rf 0.28 (E).
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hydr. Res. 2001, 330, 469–477.
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3.14. 2-Hydroxy-4-hydroxymethyl-3-(1-methylindol-3-
yl)cyclopenten-2-one (15b)
2-Hydroxy-4-hydroxymethyl-3-(1-methylindol-3-yl)
×cyclopenten-2-one (15b) was obtained and purified
similarly from 13b (20 mg, 0.033 mmol)to give 15b as
yellow crystals in 95% yield. All chromatography and
NMR parameters were the same as those of the com-
pound earlier described.8 Rf 0.38 (E), mp 221–224 °C
(CHCl3).
3.15. Penta-O-acetyl-1-deoxy-1-(1-methylindol-3-yl)-
hexitol (16b)
To a solution of 4b (100 mg, 0.2 mmol) in EtOAc (20
mL) was added 5% Pt/C (100 mg) and the mixture was
hydrogenated at 1.2 atm, then filtered, and the filtrate