Fischer indole synthesis with selected 2,3-dideoxy-D-glycero-aldopentose derivatives. Conversion of d-xylose to (2S)-3-(indol-3-YL)propane-1,2-diol

Article abstract of DOI:10.1135/cccc19960298

Two independent routes towards (2S)-3-(indol-3-yl)propane-1,2-diol (11) were achieved starting from 3,5-di-O-acetyl-1,2-O-cyclohexylidene-α-D-xylofuranose (1). Ethanethiolysis of 1 afforded acyclic diethyl dithioacetal 2 which was further O-deacetylated t

Full text of DOI:10.1135/cccc19960298

298
Lajsic, Cetkovic, Popsavin M., Popsavin V., Miljkovic:
FISCHER INDOLE SYNTHESIS WITH SELECTED 2,3-DIDEOXY-
D-glycero-ALDOPENTOSE DERIVATIVES. CONVERSION
OF D-XYLOSE TO (2S)-3-(INDOL-3-YL)PROPANE-1,2-DIOL
a
a
b
b
Stevan LAJSIC , Gordana CETKOVIC , Mirjana POPSAVIN , Velimir POPSAVIN
b
and Dusan MILJKOVIC
a Department of Applied Chemistry,
Faculty of Technology, University of Novi Sad, Cara Lazara 1, YU-21000 Novi Sad, Yugoslavia
b Institute of Chemistry,
Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovica 3, YU-21000 Novi Sad,
Yugoslavia
Received August 7, 1995
Accepted September 20, 1995
Two independent routes towards (2S)-3-(indol-3-yl)propane-1,2-diol (11) were achieved starting from
3,5-di-O-acetyl-1,2-O-cyclohexylidene-α-D-xylofuranose (1). Ethanethiolysis of 1 afforded acyclic
diethyl dithioacetal 2 which was further O-deacetylated to give 3. Selective benzoylation of 3 gave
5-O-benzoyl derivative 4. Treatment of 4 with N-bromosuccinimide in methanol gave methyl furano-
side 5 which was further desulfurized over Raney nickel to afford 6. An acid hydrolysis of 6 gave
hemiacetal 7 which upon treatment with phenylhydrazine, according to standard Fischer indolization
procedure, yielded a mixture of chiral indoles 10. O-Debenzoylation of 10 gave the crystalline diol
11. A more efficient route towards the chiral indole 11 included the initial dethioacetalation of 2 into
dimethyl acetal 8 which was further desulfurized over Raney nickel to give the corresponding 2,3-
dideoxy derivative 9. Direct Fischer indolization of 9 with phenylhydrazine, followed by O-deacetyl-
ation of intermediate 12, afforded the expected indole 11 in good yield.
Key words: Ethanethiolysis; Dethioacetalation; Fischer indol synthesis; D-Xylose.
Various indole derivatives have often been prepared by the well known Fischer indole
synthesis1, that includes an acid catalyzed cyclization of a phenylhydrazine and alde-
hyde or ketone. In connection with our recent studies on the synthesis of optically pure
non-carbohydrate molecules by chirality transfer from monosaccharides2, the Fischer
indolization of phenylhydrazine and 2,3-dideoxy-D-glycero-pentose derivatives 7 and 9
was examined, in order to prepare 3-substituted indoles bearing (2S)-propane-1,2-diol
residue as a chiral segment.
Both 7 and 9 were prepared starting from 3,5-di-O-acetyl-1,2-O-cyclohexylidene-α-D-
xylofuranose (1) which is readily available from D-xylose in three synthetic steps3.
Ethanethiolysis of 1 under the conditions similar to those already reported4, afforded
84% yield of the 4,5-di-O-acetyl-2,3-di-S-ethyl-2,3-dithio-D-ribose diethyl dithioacetal
(2). The structure of product 2 was elucidated by NMR spectra as well as on the basis
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Short Communication
299
of our earlier findings that similar ethanethiolysis of certain 1,2-O-isopropylidene-α-D-
glucofuranose derivatives gave the corresponding 2,3-di-S-ethyl-2,3-dithio-D-allose
diethyl dithioacetals in excellent yields4. Treatment of 2 with sodium methoxide in
methanol gave the corresponding diol 3 which was further selectively benzoylated to
give 5-O-benzoyl derivative 4 (85% from 2).
Reaction of diethyl dithioacetal 4 with N-bromosuccinimide in dry methanol af-
forded methyl β-furanoside 5 as the only reaction product in a yield of 90%. This
transformation is analogous to the reported method for cleavage of dithioacetals by
1
iodine–methanol reagent system5. The characteristic singlet in H NMR spectrum of 5
at δ 3.31 (3 H) together with the corresponding signal in 13C NMR spectrum (δ 54.62)
indicated the presence of OCH3 group at C-1. The low-field signal in proton NMR
spectrum at δ 5.0 ppm (brs, 1 H, J(1,2) < 1 Hz) together with the corresponding one in
1
the 13C NMR spectrum (δ 108.72 d, J = 177 Hz) unambiguously proved β-configura-
CH(SEt)2
SEt
OMe
AcOCH2
OAc
BzOCH2
O
O
SEt
O
OR
CH2OR1
R1
R1
O
R1 = SEt
R1 = H
R = R1= Ac
R = R1= H
2,
3,
4,
5,
6,
1
R = H; R1= Bz
1
CH2OR
OR1
3
2
CH(OMe)2
BzOCH2
O
4’
7’
3’
R
R
OH
9’
8’
5’
6’
2’
1’
OAc
N
H
CH2OAc
7
R, R1= Bz, H
R = R1= H
R = R1= Ac
8,
10,
11,
12,
R = SEt
9, R = H
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Lajsic, Cetkovic, Popsavin M., Popsavin V., Miljkovic:
tion of the anomeric centre. Raney nickel desulfurization of 5 in boiling dioxane–ethanol
afforded the known6 methyl 5-O-benzoyl-2,3-dideoxy-β-D-glycero-pentofuranoside (6)
in a yield of 84%. Compound 6 upon hydrolysis with diluted sulfuric acid in aqueous
dioxane gave the corresponding hemiacetal 7 in a yield of 88%.
Treatment of 7 with phenylhydrazine hydrochloride and sodium acetate in presence
of sulfuric acid as a catalyst afforded the desired indole derivative 10 as a mixture of
regio-isomers, i.e. 1-O-benzoyl and 2-O-benzoyl derivatives, in a combined yield of
75%. Obviously the Fischer indolization of 6 was followed by successive migration of
benzoyl group. O-Debenzoylation of crude mixture 10 gave crystalline (2S)-3-(indol-3-yl)-
1
propane-1,2-diol (11) as the only reaction product in a yield of 80%. Both H and 13C
spectral data for the synthesized product were consistent with the expected structure 11.
An NOE experiment performed on the product 11 was crucial in assigning the protons
from indole ring. Namely, irradiation of the low-field signal at δ 8.14 (bs, 1 H, N-H)
resulted in enhancement of both signals at δ 7.02 (bs, 1 H, H-2′) and δ 7.35 (dd, 1 H,
J = 7.9 Hz, H-7′). All of the remaining protons of 11 have unambiguously been as-
signed by homo-decoupling experiments that enabled further assignment of the correspond-
ing C-atoms in 13C NMR spectrum by using an additional 2D XHCORR experiment.
Compound 11 was also efficiently prepared by an independent route via acyclic in-
termediates 8 and 9. N-Bromosuccinimide dethioacetalation7 of compound 2 afforded
acyclic dimethyl acetal derivative 8 in a yield of 89%. Raney nickel desulfurization of
compound 8 gave 4,5-di-O-acetyl-2,3-dideoxy-D-glycero-pentose dimethyl acetal 9 in
68% yield. Compound 9 upon treatment with phenylhydrazine, according to standard
Fischer indolization procedure, afforded a mixture of indoles 11 and 12 as the major
reaction products. The crude mixture was further treated with sodium methoxide in
methanol whereupon the expected diol 11 was obtained in a yield of 65%. Treatment of
compound 11 with acetic anhydride in pyridine gave the corresponding 1,2-di-O-acetyl
derivative 12 in a yield of 73%.
It is expected that synthesized diol 11 could serve as a suitable intermediate in
planned enantiospecific syntheses of some biologically active 3-substituted indole deri-
vatives from D-xylose, including both D- and L-tryptophan, as well as (S)-indole-3-lac-
tic acid.
EXPERIMENTAL
Melting points were determined on Büchi SMP 20 apparatus and were not corrected. Optical rota-
tions were measured on automatic polarimeter Polamat A (Zeiss, Jena) at 23 °C in chloroform solu-
tions. NMR spectra (1H at 250 MHz and 13C at 62.5 MHz) were recorded on a Bruker AC 250 E
instrument in deuteriochloroform with tetramethylsilane as an internal standard. Chemical shifts are
given in ppm (δ-scale) and coupling constants (J) in Hz. Thin-layer chromatography (TLC) was per-
formed on DC Alufolien Kieselgel 60 F254 (Merck). Short column chromatography was carried out on
Kieselgel 60 (under 0.063 mm). Typical sample/adsorbent ratio was 1 : 30 (w/w). The extracts were
dried with anhydrous sodium sulfate.
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4,5-Di-O-acetyl-2,3-di-S-ethyl-2,3-dithio-D-ribose Diethyl Dithioacetal (2)
To a cooled (0 °C) and stirred solution of 3,5-di-O-acetyl-1,2-O-cyclohexylidene-α-D-xylofuranose3
(1; 3.1 g, 10 mmol) in ethane thiol (10 ml, 132 mmol) was added pre-cooled concentrated hydro-
chloric acid (10 ml). The reaction mixture was stirred at 0 °C for 3 h and then at room temperature
for additional 20 h. After neutralization with PbCO3 the precipitate was filtered off and the clear solution
extracted with ethyl acetate. The extract was washed with brine, dried and evaporated to give the
crude product 2 (4 g). After chromatographic purification on a column of silica gel (30 g; hexane–
ethyl acetate, 6 : 1), the pure 2 was obtained (3.8 g, 82%) as a colourless syrup, [α]D +18.44° (c 1.0).
1H NMR spectrum: 1.16 m, 12 H (4 × CH3 from SEt); 2.06 2 s, 2 × 3 H (2 × CH3CO); 2.88 m, 8 H
(4 × CH2 from SEt); 3.0 t, 1 H (H-2); 3.55 t, 1 H (H-3); 4.35–4.45 two overlapped dd, 2 H (H-5a
and H-5b); 4.48 d, 1 H (H-1); 5.62 m, 1 H (H-4). 13C NMR spectrum: 14.27, 14.44, 14.55 and 14.77
(4 × SCH2CH3), 20.75 and 21.97 (2 × CH3CO), 25.53, 26.23, 28.18 and 29.99 (4 × SCH2CH3), 50.3
(C-3), 56.33 (C-2), 57.3 (C-1), 63.57 (C-5), 73.35 (C-4), 169.55 and 170.54 (2 × C=O).
2,3-Di-S-ethyl-2,3-dithio-D-ribose Diethyl Dithioacetal (3)
To a solution of compound 2 (3.5 g, 8.2 mmol) in methanol (30 ml) was added a solution of sodium
methoxide in methanol (c 1 mol l–1; 10 ml). The mixture was stirred for 24 h at room temperature
and then neutralized (Dowex-50 (H+); 10 g), filtered and evaporated. The syrupy residue (2.8 g) was
chromatographed on a column of silica gel (hexane–ethyl acetate, 5 : 1) whereupon the pure 3 was
1
obtained (2.5 g, 90%) as a colourless oil, [α]D +30.45° (c 1.02). H NMR spectrum: 1.19–1.3 m, 12 H
(4 × SCH2CH3); 2.03 s, 1 H (OH); 2.56–2.89 m, 8 H (4 × SCH2CH3 ); 3.1 dd, 1 H, J(1,2) = 5.3,
J(2,3) = 7 (H-2); 3.29 t, 1 H, J(3,4) = 7.2 (H-3); 3.72 dd, 1 H, J(5a,5b) = 11.4, J(4,5a) = 6.8 (H-5a);
3.78 bs, 1 H (OH); 3.86 dd, 1 H, J(4,5b) = 3.2 (H-5b); 4.14 dt, 1 H (H-4); 4.58 d, 1 H (H-1). 13C NMR
spectrum: 14.31, 14.60, 14.66 and 15.05 (4 SCH2CH3), 25.88, 26.31, 28.32 and 30.08 (4 SCH2CH3),
53.00 (C-3), 56.97 (C-2), 57.39 (C-1), 64.59 (C-5), 73.23 (C-4).
5-O-Benzoyl-2,3-di-S-ethyl-2,3-dithio-D-ribose Diethyl Dithioacetal (4)
To a cooled (–10 °C) and stirred solution of compound 3 (2.5 g, 7.3 mmol) in pyridine (30 ml) was
added benzoyl chloride (0.95 ml, 8.8 mmol) and the resulting solution left at –10 °C for 48 h. The
reaction mixture was poured onto ice, acidified with aqueous hydrochloric acid (c 5 mol l–1) to pH 2
and extracted with ethyl acetate (3 × 30 ml). The extract was washed with brine, saturated NaHCO3
solution, dried and evaporated. The oily residue was purified on a column of silica gel (cyclohexane–ethyl
acetate, 6 : 1) to yield the pure 4 (3.2 g, 98%). 1H NMR spectrum: 1.10–1.33 m, 12 H (4 × SCH2CH3);
2.47–3.00 m, 8 H (4 × SCH2CH3); 3.10 bs, 1 H (OH); 3.15 t, 1 H, J(1,2) = J(2,3) = 6.5 (H-2); 3.50 t,
1 H, J(3,4) = 7.3 (H-3); 4.47 m, 1 H, J(4,5a) = 5, J(4,5b) = 3 (H-4); 4.53–4.67 m, 3 H (H-1 and 2 H-5);
7.36–8.10 m, 5 H (Bz). 13C NMR spectrum: 14.35, 14.59, 14.63 and 15.12 (4 × SCH2CH3), 25.72,
26.29, 28.41 and 30.2 (4 × SCH2CH3), 52.78 (C-3), 57.07 (C-2), 57.81 (C-1), 67.46 (C-5), 71.74
(C-4), 128.44, 129.54, 129.78, 129.84 and 133.22 (ArC), 166.89 (C=O).
Methyl 5-O-Benzoyl-2,3-di-S-ethyl-2,3-dithio-β-D-ribofuranoside (5)
N-Bromosuccinimide (2.5 g, 14 mmol) was added in portions to a stirred and cooled (0 °C) solution
of compound 4 (2.5 g, 5.6 mmol) in methanol (30 ml). The mixture was stirred at 0 °C for 10 min
and then poured into cold solution of Na2S2O3 . 5 H2O (2.5 g) and NaHCO3 (3 g) in water (100 ml).
The resulting suspension was stirred for 20 min and extracted with ethyl acetate. The extract was
washed with brine, dried and concentrated to an oil. After chromatographic purification on a column
of silica gel (hexane–ethyl acetate, 5 : 1) the pure product 5 was obtained (1.8 g, 90%) as a colour-
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Lajsic, Cetkovic, Popsavin M., Popsavin V., Miljkovic:
1
less oil. H NMR spectrum: 1.29 m, 6 H (2 × SCH2CH3); 2.63 m, 4 H (2 × SCH2CH3); 3.31 s, 3 H
(OCH3); 3.45 d, 1 H (H-2); 3.78 dd, 1 H (H-3); 4.28 m, 1 H (H-4); 4.4 dd, 1 H (H-5a); 3.31 s, 3 H
(OCH3); 3.45 d, 1 H (H-2); 3.78 dd, 1 H (H-3); 4.28 m, 1 H (H-4); 4.4 dd, 1 H (H-5a); 4.65 dd, 1 H
(H-5b); 5.0 s, 1 H (H-1); 7.32–8.16 m, 5 H (Bz). 13C NMR spectrum: 14.28 and 14.63 (2 × SCH2CH3),
26.2 and 26.77 (2 × SCH2CH3), 47.15 and 54.35 (C-2 and C-3), 64.58 (C-5), 82.03 (C-4), 108.72
(C-1), 128.2, 129.52, 129.82 and 132.9 (ArC), 166.06 (C=O).
Methyl 5-O-Benzoyl-2,3-dideoxy-β-D-glycero-pentofuranoside (6)
A suspension of Raney nickel (20 ml) in ethanol (40 ml) was added to a solution of compound 5 (1.8 g,
5 mmol) in a mixture of dioxane (25 ml) and ethanol (25 ml). The mixture was vigorously stirred at
reflux temperature for 2 h. The suspension was filtered through a Celite pad and the catalyst was
washed with a mixture of dioxane–ethanol (1 : 1), the filtrate and washings were combined and evapo-
rated in vacuo. Silica gel column chromatography (hexane–ethyl acetate, 5 : 1) of the residue afforded
pure 6 (1 g, 84%) as a colourless syrup, [α]D –72.6° (c 1.71); literature6 gives [α]D –73° (c 1.8).
5-O-Benzoyl-2,3-dideoxy-D-glycero-pentofuranose (7)
To a solution of compound 6 (1 g, 4.2 mmol) in dioxane (15 ml) was added aqueous H2SO4 (c 2 mol l–1; 5
ml) and the resulting mixture was stirred at 100 °C for 5 h. The reaction mixture was neutralized by
stirring with an excess of CaCO3, filtered and concentrated to give chromatographically homogeneous
1
hemiacetal 7 (0.8 g, 88%) as a colourless oil (1 : 1 mixture of α- and β-anomers). H NMR spectrum:
1.20–2.36 m, 4 H (2 H-2 and 2 H-3); 3.94–4.52 m, 4 H (H-4, 2 H-5 and OH); 5.61 m, 1 H (H-1α and
H-1β); 7.36–8.12 m, 5 H (ArH). 13C NMR spectrum: 25.52 and 25.73 (C-3), 32.57 and 33.38 (C-2),
66.55 and 68.0 (C-5), 75.85 and 77.9 (C-4), 98.72 and 98.9 (C-1), 128.27, 129.62, 129.84, 129.9 and
132.96 (ArC), 166.42 and 166.53 (C=O).
4,5-Di-O-acetyl-2,3-di-S-ethyl-2,3-dithio-D-ribose Dimethyl Acetal (8)
To a stirred and cooled (0 °C) solution of compound 2 (3.26, 7.61 mmol) in methanol (30 ml) was
added N-bromosuccinimide (3.26 g, 18.2 mmol) in portions. The mixture was stirred at 0 °C for 10
min, then poured into cold water (200 ml) containing NaHCO3 (5 g) and Na2S2O3 (5 g) and extracted with
ethyl acetate (3 × 100 ml). The combined extracts were washed with brine, dried and concentrated,
1
to afford chromatographically pure 8 (2.3 g, 89%) as a colourless oil, [α]D +38.1° (c 1.2). H NMR
spectrum: 1.25 t, 6 H (2 × SCH2CH3 from 2 SEt); 2.08 2 s, 6 H (2 × CH3COO); 2.71 m, 4 H (2 ×
SCH2CH3); 3.18 m, 1 H (H-2); 3.30 m, 1 H (H-3); 3.41 2 s, 6 H (2 × OCH3); 4.35 m, 1 H (H-5a);
4.53 d, 1 H (H-1); 4.63 m, 1 H (H-5b); 5.2 m, 1 H (H-4). 13C NMR spectrum: 14.62 and 14.72 (2 ×
SCH2CH3), 20.8 and 21.11 (2 × CH3COO), 27.76 and 28.23 (2 × SCH2CH3), 48.54 (C-3), 51.96
(C-2), 55.79 and 56.21 (2 × CH3O), 63.32 (C-4), 108.12 (C-1), 169.52 and 170.56 (2 × C=O).
4,5-Di-O-acetyl-D-glycero-pentose Dimethyl Acetal (9)
To a solution of compound 8 (1.0 g, 2.67 mmol) in dioxane was added a suspension of Raney nickel
(23 g) in ethanol (20 ml). The mixture was refluxed for 2 h, then filtered through Celite pad. The
catalyst was washed with hot ethanol and the combined filtrates and washings were concentrated in
vacuo. Silica gel column chromatography (cyclohexane–ethyl acetate, 3 : 1) of the residue afforded
1
pure 9 (0.5 g, 68%) as a colourless oil, [α]D –1.73° (c 1.16). H NMR spectrum: 1.3 m, 4 H (2 H-2
and 2 H-3); 2.1 d, 6 H (2 × CH3COO); 3.35 s, 6 H (2 × OCH3); 4.2 m, 2 H (2 H-5); 4.35 m, 1 H
(H-1); 5.05 m, 1 H (H-4).
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(2S)-3-(Indol-3-yl)propane-1,2-diol (11)
A) The solution of phenylhydrazine hydrochloride (1 g, 6.92 mmol) and sodium acetate (1 g,
12.19 mmol) in ethanol (30 ml) was stirred under nitrogen for 30 min. The solution of hemiacetal 7
(0.8 g, 3.6 mmol), mixture of anomers in ethanol (10 ml) was then added and the resulting mixture
stirred at room temperature for 1 h. The solution was acidified with aqueous H2SO4 (c 1 mol l–1; 10 ml)
and refluxed while stirring for the additional 2 h. The reaction mixture was neutralized with an ex-
cess of CaCO3 and filtered. The solvents were removed by co-distillation with toluene to give an oily
residue which was chromatographed on a column of silica gel (cyclohexane–ethyl acetate, 4 : 1) to
1
afford an inseparable mixture of 1- and 2-O-benzoyl derivatives 10 (0.8 g, 75%), as an oil. H NMR
spectrum (selected signals): 2-O-benzoyl derivative: 2.25 bs, 1 H (OH); 3.21 m, 2 H (2 H-3); 3.8 m,
2 H (2 H-1); 5.45 m, 1 H (H-2); 1-O-benzoyl derivative: 3.02 m, 2 H (2 H-3); 4.4 m, 3 H (2 H-1)
and H-2). 13C NMR spectrum (selected signals): 2-O-benzoyl derivative: 26.33 (C-3), 63.9 (C-1),
76.16 (C-2); 1-O-benzoyl derivative: 29.72 (C-3), 68.32 (C-1), 76.16 (C-2). To a solution of 1- and
2-O-benzoyl derivatives 10 (0.6 g, 2.03 mmol) in methanol (10 ml) was added a solution of sodium
methoxide in methanol (c 0.43 mol l–1; 10 ml). The mixture was stirred at room temperature for 16 h
and then neutralized (Dowex-50 (H+); 5 g) filtered and evaporated. The crude residue (0.5 g) was
chromatographed on a column of silica gel (dichloromethane–acetone, 1 : 1) to give pure 11 (0.31 g,
80%), m.p. 60–62 °C, [α]D –21.9° (c 1.0).
B) To a stirred solution of compound 9 (0.5 g, 2 mmol) and phenylhydrazine hydrochloride (0.5 g,
3.47 mmol) in ethanol (20 ml) was added concentrated H2SO4 (0.5 ml) in portions. The reaction mixture
was refluxed for 2 h and then poured into ice and water (150 ml) and ectracted with ethyl acetate
(3 × 50 ml). The combined extracts were washed with brine (to pH 7), dried and evaporated. The
crude mixture was treated with sodium methoxide in methanol as described above (procedure A) to
1
give pure 11 (0.25, 65%) as colourless crystals, m.p. 61–62 °C, [α]D –21.87° (c 0.96). H NMR spec-
trum: 2.7 bs, 2 H (2 × OH); 2.81–3.01 m, 2 H, J(3a,3b) = 14.6, J(2,3a) = 7.8, J(2.3b) = 5.5 (H-3a
and H-3b); 3.54 dd, 1 H, J(1a,1b) = 11.2, J(1a,2) = 6.9 (H-1a); 3.71 dd, 1 H, J(1b,2) = 3.2 (H-1b);
4.02 m, 1 H (H-2); 7.02 s, 1 H (H-2′); 7.14 dt, 1 H, J(4′,5′) = 7.5, J(5′,6′) = 6.9, J(5′,7′) = 1.3 (H-5′);
7.22 dt, 1 H, J(6′,7′) = 7.9, J(4′,6′) = 1.2 (H-6′); 7.35 d, 1 H (H-7′); 7.61 d, 1 H (H-4′); 8.14 bs, 1 H
(NH). 13C NMR spectrum: 29.28 (C-3), 66.28 (C-1), 72.03 (C-2), 111.33 (C-7′), 111.44 (C-3′),
118.87 (C-4′), 119.61 (C-5′), 122.28 (C-6′), 123.01 (C-2′), 127.52 (C-8′), 136.4 (C-9′). For
C11H13NO2 (191.1) calculated: 69.07% C, 6.86% H, 7.33% N; found: 68.82% C, 6.92% H, 7.00% N.
(2S)-3-(Indol-3-yl)propane-1,2-diol Diacetate (12)
A solution of compound 11 (0.19 g, 1.0 mmol) and acetic anhydride (1 ml, 10.6 mmol) in pyridine
(5 ml) was stored at room temperature for 16 h. The reaction mixture was poured onto ice acidified
with diluted hydrochloric acid (c 2 mol l–1) to pH 2 and extracted with ethyl acetate. The extract was
washed with brine, dried and evaporated to give a chromatographically homogeneous di-O-acetyl
1
derivative 12 (0.2 g, 73%) as a colourless oil, [α]D –80.5° (c 1.23). H NMR spectrum: 2.07 and 2.08
2 s, 6 H (2 × CH3COO); 3.04 dd, 1 H J(3a,3b) = 13.8, J(2,3a) = 7.6 (H-3a); 3.14 dd, 1 H, J(2,3b) =
5.8 (H-3b); 4.09 dd, 1 H, J(1a,1b) = 11.9, J(1a,2) = 6.4 (H-1a); 4.26 dd, 1 H, J(1b,2) = 3.3 (H-1b);
5.37 m, 1 H (H-2); 7.06 s, 1 H J(NH,2′) = 2.2 (H-2′); 7.18 m, 2 H (H-5′ and H-6′); 7.38 dd, 1 H,
J(6′,7′) = 7.4, J(5′,7′) = 1.5 (H-7′); 7.70 d, 1 H, J(4′,5′) = 7.45 (H-4′); 8.16 bs, 1 H (NH). 13C NMR
spectrum: 20.82 and 21.2 (2 × CH3COO), 29.69 (C-3), 64.47 (C-1), 71.8 (C-2), 110.63 (C-3′), 111.13
(C-7′), 118.9 (C-4′), 119.62 (C-5′), 122.23 (C-6′), 122.61 (C-2′), 136.13 (C-9′), 170.55 and 170.8
(2 × C=O).
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This work was supported by the Serbian Ministry of Science and Technology.
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