Stereospecific synthesis of (-)-allo-muscarine from D-glucose: Novel routes to the key chiral synthon

Article abstract of DOI:10.1135/cccc19970809

The key chiral synthon in a novel synthesis of (-)-allo-muscarine from D-glucose has been prepared by three independent routes. The most efficient one includes a four-step conversion via the 4-O-benzoyl derivatives of starting 2,5-anhydro-3,5-di-O-methanesulfonyl-L-idose ethylene acetal (2a) into 2,5-anhydro-3,6-dideoxy-L-lyxo-hexose ethylene acetal (4b). The intermediate 4b was efficiently converted into the chiral synthon 2,5-anhydro-4-O-benzoyl-3,6-dideoxy-L-arabino-hexose (4c) by Mitsunobu reaction.

Full text of DOI:10.1135/cccc19970809

2,5-Anhydro Sugars
809
STEREOSPECIFIC SYNTHESIS OF (–)-allo-MUSCARINE FROM
D-GLUCOSE: NOVEL ROUTES TO THE KEY CHIRAL SYNTHON
a
a
a
a
Velimir POPSAVIN , Ostoja BERIC , Mirjana POPSAVIN , Janos CSANADI ,
b
a
Stevan LAJSIC and Dusan MILJKOVIC
a Institute of Chemistry, Faculty of Sciences, University of Novi Sad, Trg. D. Obradovica 3,
21000 Novi Sad, Yugoslavia
b Department of Applied Chemistry, Faculty of Technology, University of Novi Sad, Cara Lazara 1,
21000 Novi Sad, Yugoslavia
Received November 13, 1996
Accepted December 27, 1996
The key chiral synthon in a novel synthesis of (–)-allo-muscarine from D-glucose has been prepared
by three independent routes. The most efficient one includes a four-step conversion via the 4-O-ben-
zoyl derivatives of starting 2,5-anhydro-3,5-di-O-methanesulfonyl-L-idose ethylene acetal (2a) into
2,5-anhydro-3,6-dideoxy-L-lyxo-hexose ethylene acetal (4b). The intermediate 4b was efficiently con-
verted into the chiral synthon 2,5-anhydro-4-O-benzoyl-3,6-dideoxy-L-arabino-hexose (4c) by Mitsu-
nobu reaction.
Key words: 2,5-Anhydro sugars; D-Glucose; (–)-allo-Muscarine; 3,6-Thioanhydro sugars.
(–)-allo-Muscarine (1) is a C-2 epimer of (+)-muscarine which occurs in the mushroom
Amanita muscaria1, and shows cholinomimetic activity2. There is a renewed interest in
the muscarinic field due to the discovery of a relationship between cholinergic deficits
and the pathology of Alzheimer’s disease3. The synthesis of muscarine and many of its
analogues have been reviewed4, but only few syntheses of (–)-allo-muscarine (1) have
been achieved so far5. Recently we have completed a stereospecific synthesis of 1
based on D-glucose as a chiral precursor6. However, due to some relatively low-yield
steps in the reported route6, new efforts have been made in order to improve the prepa-
ration of the key chiral intermediate 4c and (–)-allo-muscarine (1) itself. We now report
two independent routes, one via intermediate 3b and second via 4b with three alterna-
tive in 4b preparation, towards the key chiral synthon in an alternative synthesis of
(–)-allo-muscarine from D-glucose.
Ethylene acetal of 2,5-anhydro-3,5-di-O-methanesulfonyl-L-idose (2a) which is readily
available from D-glucose7 was treated with triflic anhydride in pyridine and dichloro-
methane whereupon the corresponding 4-triflate 2b was obtained in 93% yield. The
earlier findings8 that some sugar triflates when reacted with sodium nitrite in N,N-di-
methylformamide gave the corresponding epi-hydroxy compounds prompted us to in-
vestigate the possible use of this reagent for conversion of 2b into the corresponding
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alcohol with inverted configuration. A treatment of 2b with sodium nitrite in N,N-di-
methylformamide afforded the corresponding 2,5-anhydro-L-altrose derivative 2c in a
yield of only 29%. Reaction of 2c with benzoyl chloride in pyridine gave the corre-
sponding 4-O-benzoyl derivative 2d, which was further treated with sodium hydrogen
sulfide in N,N-dimethylformamide to afford the bicyclic oxathiane derivative 3b (25%
from 2c). The intermediate 3b was alternatively also prepared by direct sodium hy-
drogen sulfide mediated cyclization of 2c to alcohol 3a which was subsequently ben-
zoylated to give 3b (38% from 2c). Raney nickel desulfurization of 3b afforded the
chiral synthon 4c (67%) with all chiral centers corresponding to (–)-allo-muscarine (1).
O
1
CH NMe
2
3
O
O
5
O
2
1
Ms O
OH
4
R
X
Me
6
Ms OH C
2
3
R
1
R
(-)-allo-Muscarine (1)
2
R
X = OH or Halogen
a
b
c
d
e
f
OH
OTf
H
H
H
OH
OBz
H
OMs H
OBz H
O
O
O
O
O
O
1
1
R
R
Me
R
R
S
1
1
R
3
R
R
4
R
a
b
c
d
e
H
H
OH
OBz
a
b
c
OBz H
OH
H
H
OBz
OMs H
OH
OBz
H
H
Ms = CH SO , Tf = CF SO
2
3
2
3
Although the 1H and 13C NMR data as well as the optical rotation of 4c were in good
agreement with those already reported6, the relatively low overall yield of the present
route (6.9% from 2a) prompted a further study directed towards preparation of 4c by an
alternative synthetic sequence via the 3,6-dideoxy derivative 4b as a key intermediate.
Successive inter- and intramolecular attack of hydrogen sulfide anion on trimesylate6
2e led to the bicyclic oxathiane derivative 3c, which was immediately treated with
sodium methoxide in methanol to afford the corresponding alcohol 3d (33% from 2e).
Raney nickel desulfurization of 3d gave the expected 3,6-dideoxy derivative 4b in an
overall yield of 27% with respect to trimesylate 2e. However, when the intermediate 3d
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2,5-Anhydro Sugars
811
was prepared directly from 2a (by its treatment with NaSH in DMF), the same inter-
mediate 4b was obtained in an overall yield of 35% related to starting compound 2a.
Finally, the best overall yield of desired intermediate 4b has been achieved by alter-
native chemical transformations of dimesylate 2a under the conditions similar to those
already reported7. Treatment of 2a with benzoyl chloride in pyridine gave the corres-
ponding 4-O-benzoyl derivative 2f, which was immediately treated with sodium hy-
drogen sulfide in N,N-dimethylformamide to give the expected oxathiane derivative 3e.
Raney nickel desulfurization of 3e to the corresponding 3,6-dideoxy derivative 4a was
followed by the subsequent debenzoylation of 4a to 4b. All four steps concerning the
conversion of 2a to 4b were carried out successively, whereupon the intermediates 2f,
3e, and 4a were used in the subsequent steps without any purification. Pure product 4b
was isolated by column chromatography in an overall yield of 63% related to the start-
ing compound 2a.
Alcohol 4b readily reacted with triphenylphosphine, diethyl azodicarboxylate and
benzoic acid, under standard Mitsunobu9 conditions, to afford the chiral synthon 4c in
82% yield.
In conclusion, the sequence which uses the crude 4-O-benzoyl derivatives (2f, 3e,
and 4a) as intermediates is the most convenient route towards the key chiral intermedi-
ate 4c since it provides the highest overall yield of the final product (52% from 2a)
achieved by a simple preparative procedure. This result represents a significant im-
provement in respect to the reported route6 which afforded the chiral synthon 4c in a
much lower overall yield6 (23% in respect to the same starting compound 2a).
Since (–)-allo-muscarine has already been obtained6 from 4-O-benzoyl derivative 4c,
the chemical transformations described in this paper formally represent an alternative
synthesis of (–)-allo-muscarine from D-glucose.
EXPERIMENTAL
Melting points were determined on a Büchi SMP 20 apparatus and were not corrected. Optical rota-
tions were measured on a Perkin–Elmer 141 MC polarimeter at 23 °C in chloroform solutions. NMR
spectra (1H at 250 MHz and 13C at 62.9 MHz) were recorded on a Bruker AC 250 E instrument in
deuteriochloroform. Chemical shifts are expressed in ppm (δ-scale) downfield from tetramethylsilane.
Coupling constants (J) are given in Hz. Column chromatography (Kieselgel 60 under 0.063 mm;
Merck) and flash column chromatography (ICN Silica 32-63) were carried out with the following
solvent mixtures: Petroleum ether–Me2CO, 4 : 1 (S1); CH2Cl2–Me2CO, 9 : 1 (S2); 49 : 1 (S3), 99 : 1
(S4), 4 : 1 (S5); Et2O (S6); toluene–Me2CO, 49 : 1 (S7), 4 : 1 (S8); CHCl3 (S9); hexane–EtOAc, 1 : 1
(S10); toluene–EtOAc, 4 : 1 (S11); CH2Cl2–EtOAc, 49 : 1 (S12). All organic extracts were dried
with anhydrous Na2SO4. Organic solutions were concentrated in a rotary evaporator under diminished
pressure at bath temperature 30–35 °C.
2,5-Anhydro-3,6-di-O-methanesulfonyl-4-O-trifluoromethanesulfonyl-L-idose Ethylene Acetal (2b)
To a stirred and ice-cooled solution of dimesylate 2a (2.6 g; 7.2 mmol) in dry pyridine (3.6 ml; 44.7 mmol)
and dichloromethane (60 ml) was added trifluoromethanesulfonic anhydride (2.6 ml; 15.5 mmol) in
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portions. The mixture was stirred at 0 °C for 1 h then diluted with dichloromethane (60 ml), washed
successively with aqueous 10% hydrochloric acid (50 ml) and water (4 × 100 ml), dried and eva-
porated. Flash chromatography (S1) of the residue gave pure 2b (3.3 g; 93%) as a white solid. Re-
crystallization from methanol afforded an analytical sample 2b as colourless needles, m.p. 94 °C,
[α]D –1.2° (c 0.5). 1H NMR spectrum: 3.10 s and 3.17 s, 2 × 3 H (2 × CH3SO2); 3.89–4.1 m, 4 H
(dioxolane CH2); 4.25 dd, 1 H, J(1,2) = 5.3, J(2,3) = 4.7 (H-2); 4.34 dd, 1 H, J(6a,6b) = 11.1, J(5,6a) = 6.3
(H-6a); 4.49 dd, 1 H, J(5,6b) = 5.5 (H-6b); 4.74 ddd, 1 H, J(4,5) = 4.2, J(5,6a) = 6.3, J(5,6b) = 5.5
(H-5); 5.14 d, 1 H (H-1); 5.3 dd, 1 H, J(2,3) = 4.7, J(3,4) = 2.5 (H-3); 5.62 dd, 1 H (H-4). 13C NMR
spectrum: 37.39 and 38.03 (2 × CH3SO2), 64.97 (C-6), 65.24 and 65.37 (dioxolane CH2), 76.38 (C-5),
78.71 (C-2), 80.12 (C-3), 86.6 (C-4), 100.99 (C-1), 118.11 q, 1J(C,F) = 320 (CF3SO2). For
C11H17F3O12S3 . CH3OH (526.5) calculated: 27.38% C, 4.02% H, 18.27% S; found: 27.23% C,
3.76% H, 18.23% S.
2,5-Anhydro-3,6-di-O-methanesulfonyl-L-altrose Ethylene Acetal (2c)
To a solution of triflate 2b (1.8 g; 3.6 mmol) in N,N-dimethylformamide (20 ml) was added finely
powdered sodium nitrite (4.0 g; 58.0 mmol). The mixture was stirred for 24 h at 35 °C, then filtered
and concentrated in vacuo. Column chromatography (S2) of the residue yielded pure 2c (0.38 g;
29%) as colorless oil. The oily residue was crystallized from dichloromethane–hexane to give an ana-
1
lytical sample of 2c as colorless needles, m.p. 116 °C, [α]D +0.8° (c 0.2). H NMR spectrum: 3.08 s and
3.18 s, 2 × 3 H (2 × CH3SO2); 3.46 d, 1 H, J(4,OH) = 7.4 (OH); 3.88–4.08 m, 4 H (dioxolane CH2);
4.11 dd, 1 H, J(1,2) = 5.5, J(2,3) = 4.2 (H-2); 4.18 m, 1 H, J(5,6a) = 3.4, J(5,6b) = 2.6 (H-5); 4.37 dd,
1 H, J(5,6a) = 3.4, J(6a,6b) = 11.6 (H-6a); 4.4 m, 1 H, J(3,4) = 4.5 (H-4); 4.47 dd, 1 H, J(5,6b) = 2.6,
J(6a,6b) = 11.6 (H-6b); 5.13 d, 1 H, J(1,2) = 5.5 (H-1); 5.21 dd, 1 H, J(2,3) = 4.2, J(3,4) = 4.5 (H-3).
13C NMR spectrum: 37.52 and 38.89 (2 × CH3SO2), 65.27 and 65.46 (dioxolane CH2), 68.34 (C-6),
70.92 (C-4), 79.07 (C-2), 80.29 (C-5), 80.91 (C-3), 101.60 (C-1). For C10H18O10S2 (362.4) calcu-
lated: 33.15% C, 5.01% H, 17.66% S; found: 32.78% C, 4.71% H, 17.23% S.
2,5-Anhydro-4-O-benzoyl-3,6-di-O-methanesulfonyl-L-altrose Ethylene Acetal (2d)
To a solution of hydroxy derivative 2c (0.48 g; 1.3 mmol) in dry pyridine (5 ml) was added benzoyl
chloride (0.50 ml; 4.3 mmol). The mixture was stored at room temperature for 24 h, then acidified
with aqueous hydrochloric acid (1 : 1; 15 ml) and extracted with dichloromethane (4 × 10 ml). The
extracts were combined, successively washed with water and saturated aqueous sodium hydrogen car-
bonate, dried and concentrated to an oil. Flash chromatography (S6) of the residue gave 2d (0.5 g; 81%)
1
as a colorless syrup, [α]D –12.9° (c 0.2). H NMR spectrum: 3.09 s and 3.11 s, 2 × 3 H (2 × CH3SO2);
3.86–4.15 m, 4 H (dioxolane CH2); 4.16 dd, 1 H, J(1,2) = 6.6, J(2,3) = 3.2 (H-2); 4.45 dd, 1 H,
J(6a,6b) = 11.2, J(5,6a) = 3.2 (H-6a); 4.49–4.69 m, 2 H, J(5,6b) = 2.2, J(4,5) = 8.4 (H-5 and H-6b);
5.21 d, 1 H (H-1); 5.44 t, 1 H, J(2,3) = 3.2, J(3,4) = 3.4 (H-3); 5.61 dd, 1 H, J(3,4) = 3.4, J(4,5) = 8.4
(H-4); 7.41–8.20 m, 5 H (ArH). 13C NMR spectrum: 37.33 and 38.7 (2 × CH3SO2), 65.01 and 65.2
(dioxolane CH2), 68.14 (C-6), 70.96 (C-4), 77.4 (C-5), 79.63 (C-2), 80.00 (C-3), 101.41 (C-1),
128.38, 129.96 and 133.60 (ArC), 165.50 (C=O).
2,5-Anhydro-3,6-thioanhydro-L-mannose Ethylene Acetal (3a)
To a solution of dimesylate 2c (0.145 g; 0.40 mmol) in N,N-dimethylformamide (3 ml) was added
NaSH monohydrate (0.15 g; 2.0 mmol). The mixture was stirred in an atmosphere of nitrogen at 90 °C
for 1.5 h, then poured into aqueous 10% NaHCO3 (10 ml) and extracted with CH2Cl2 (4 × 10 ml).
The combined extracts were washed with water (2 × 20 ml), dried and evaporated to a brown oil.
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Flash chromatography (S3) of the residue (0.05 g) yielded pure product 3a (0.039 g; 48%) as a pale-
yellow syrup, [α]D –256.4° (c 0.1). 1H NMR spectrum: 2.89 dd, 1 H, J(6a,6b) = 10.9, J(5,6a) = 1 (H-6a);
2.98 dd, 1 H, J(5,6b) = 2.4, J(6a,6b) = 10.9 (H-6b); 3.14 d, 1 H, J(3,4) = 1.3 (H-3); 3.88–4.12 m, 4 H
(dioxolane CH2); 4.38 m, 2 H (H-4 and H-5); 4.58 d, 1 H, J(1,2) = 2.3 (H-2); 4.78 d, 1 H, J(4,OH) = 9.9
(OH); 5.05 d, 1 H (H-1). 13C NMR spectrum: 32.44 (C-6), 45.43 (C-3), 65.35 and 65.56 (dioxolane
CH2), 79.20 (C-4), 80.25 (C-5), 88.53 (C-2), 102.37 (C-1).
2,5-Anhydro-4-O-benzoyl-3,6-thioanhydro-L-mannose Ethylene Acetal (3b)
A) Treatment of 4-O-benzoyl derivative 2d (0.44 g; 0.94 mmol) with NaSH monohydrate (0.35 g;
4.7 mmol) in N,N-dimethylformamide (10 ml) for 4 h, under the same reaction conditions as de-
scribed above for 3a, afforded crude 3b (0.4 g). Column chromatography (40 g; S7) gave pure pro-
duct 3b (0.09 g; 31%) as a pale-yellow syrup.
B) Following the procedure described above for 2d, a solution of 3a (0.045 g; 0.22 mmol) and
benzoyl chloride (0.10 ml; 0.86 mmol) in dry pyridine (1 ml) gave crude product 3b. Flash chroma-
tography (S9) afforded pure product 3b (0.054 g; 79%) as a bright-yellow syrup, [α]D –39.6° (c 2.1).
1H NMR spectrum: 3.02 dd, 1 H, J(6a,6b) = 10.8, J(5,6a) = 1 (H-6a); 3.11 dd, 1 H, J(5,6b) = 2.3,
J(6a,6b) = 10.8 (H-6b); 3.64 d, 1 H, J(3,4) = 1.5 (H-3); 3.68–4.02 m, 4 H (dioxolane CH2); 4.33 d,
1 H, J(1,2) = 7.2 (H-2); 4.79 m, 1 H (H-5); 5.09 d, 1 H, J(1,2) = 7.2 (H-1); 5.44 d, 1 H, J(3,4) = 1.5
(H-4); 7.35–8.06 m, 5 H (ArH). 13C NMR spectrum: 32.82 (C-6), 44.83 (C-3), 64.91 and 65.34 (di-
oxolane CH2), 78.17 (C-5), 79.77 (C-4), 89.99 (C-2), 102.96 (C-1), 128.63, 129.44, 129.77 and
133.53 (ArC), 165.84 (C=O).
2,5-Anhydro-3,6-thioanhydro-L-talose Ethylene Acetal (3d)
A) Treatment of trimesylate6 2e (3.47 g; 7.9 mmol) with NaSH monohydrate (4.58 g; 61.9 mmol)
in N,N-dimethylformamide (23 ml) for 3 h under the same reaction conditions as described above for 3a
afforded crude oxathiane 3c (1.2 g) which was immediately treated with 1.6 M solution of NaOMe in
MeOH (15 ml) for 3 h at reflux temperature. The reaction mixture was acidified with glacial AcOH
to pH 6 and concentrated. The residue was partitioned between CH2Cl2 (15 ml) and water (20 ml).
The organic layer was separated and aqueous solution extracted with CH2Cl2 (2 × 15 ml). The com-
bined extracts were dried and evaporated to a yellow syrup. Column chromatography (100 g; S4) of
the residue afforded pure product 3d (0.45 g; 33%) as a colorless syrup.
B) Treatment of dimesylate 2a (2.5 g; 6.9 mmol) with NaSH monohydrate (2.5 g; 33.78 mmol) in
N,N-dimethylformamide (30 ml) for 24 h, under the same reaction conditions as described above for
3a yielded crude product 3d. Column chromatography (140 g; S10) of the residue (1.4 g) yielded
1
pure product 3d (0.6 g; 43%) as a colorless syrup, [α]D –24.5° (c 1.2). H NMR spectrum: 2.68 d, 1 H,
J(4,OH) = 10.3 (OH); 3.00 m, 2 H (2 H-6); 3.38 d, 1 H, J(3,4) = 2.4 (H-3); 3.83–4.05 m, 4 H (di-
oxolane CH2); 4.2 d, 1 H, J(1,2) = 4.4 (H-2); 4.34 m, 1 H (H-5); 4.74 m, 1 H (H-4); 4.80 d, 1 H
(H-1). 13C NMR spectrum: 34.1 (C-6), 49.6 (C-3), 64.9 and 65.1 (dioxolane CH2), 73.5 (C-4), 77.5
(C-5), 87.5 (C-2), 102.5 (C-1).
2,5-Anhydro-3,6-dideoxy-L-lyxo-hexose Ethylene Acetal (4b)
A) A suspension of compound 3d (1.08 g; 5.29 mmol) and Raney nickel (10 ml) in ethanol (30 ml)
was hydrogenated at 85–90 °C and normal pressure of H2 for 1 h. The mixture was diluted with a
mixture of EtOAc–EtOH (1 : 1, 60 ml), filtered through a Celite pad and the catalyst was washed
with mixture of EtOAc–EtOH (1 : 1, 80 ml). The filtrate and washing were combined and evaporated
in vacuo. The residue was treated with boiling CH2Cl2 (20 ml), then filtered and the solvent evaporated.
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Column chromatography (80 g; S5) of the residue (0.9 g) afforded pure compound 4b (0.76 g; 82%)
as a colorless syrup.
B) A solution of alcohol 2a (0.50 g; 1.4 mmol) and benzoyl chloride (0.40 ml; 3.4 mmol) in dry
pyridine (5 ml) was left at room temperature for 24 h. After the usual workup, the residue (0.85 g of
crude 2f) was treated with NaSH monohydrate (0.6 g; 8.1 mmol) in N,N-dimethylformamide (10 ml)
for 3 h, according to the procedure described above for 3a. The crude oxathiane 3e (0.5 g) thus ob-
tained was dissolved in ethanol (15 ml) and hydrogenated in the presence of Raney nickel suspension
(5 ml) at 80 °C for 1 h, whereupon the corresponding 3,6-dideoxy derivative 4a was formed. To the
reaction mixture was then added NaOH (0.07 g) and the stirring continued for 0.5 h at 80 °C. After
workup as described above (procedure A), the remaining crude 4b (0.248 g) was purified by column
chromatography (30 g; S8) to afford pure product 4b (0.151 g; 63%) as a colorless syrup, [α]D
+19.5° (c 1.9). 1H NMR spectrum: 1.22 d, 3 H, J(5,6) = 6.4 (Me-5); 2.05 m, 2 H (2 H-3); 2.26 bs,
1 H (OH); 3.84–4.04 m, 5 H (dioxolane CH2 and H-5); 4.17 ddd, 1 H, J(4,5) = 3, J(3a,4) = 1.9,
J(3b,4) = 4.2 (H-4); 4.19 ddd, 1 H, J(1,2) = 4.2, J(2,3a) = 7.5, J(2,3b) = 8.2 (H-2); 4.84 d, 1 H,
J(1,2) = 4.2 (H-1). 13C NMR spectrum: 14.0 (C-6), 36.2 (C-3), 65.1 and 65.4 (dioxolane CH2), 73.6
(C-4), 77.0 (C-2), 78.9 (C-5), 104.8 (C-1).
2,5-Anhydro-4-O-benzoyl-3,6-dideoxy-L-arabino-hexose (4c)
A) To a solution of compound 3b (0.054 g; 0.17 mmol) in EtOH (5 ml) was added a suspension
of Raney nickel (1 ml). The mixture was hydrogenated under the same reaction conditions as de-
scribed above for 4b (procedure A). After the usual workup, the remaining crude 4c was purified by
column chromatography (10 g; S7) to afford pure product 4c (0.032 g; 67%) as a colorless syrup.
B) To a stirred and ice-cooled solution of alcohol 4b (0.20 g; 1.2 mmol), benzoic acid (0.30 g; 2.5 mmol)
and triphenylphosphine (1.30 g; 5.0 mmol) in dry THF (20 ml) was added dropwise a solution of
diethyl azodicarboxylate (1.0 ml; 6.4 mmol) in dry THF (5 ml). The mixture was stirred at 0 °C for
20 min and then at room temperature for 20 h. The solvent was evaporated off and the residue was
column chromatographed (100 g; S11), to afford 4c contamined with an equal amount of aromatic
impurities as estimated by NMR. Repeated column chromatography (50 g; S12) of the mixture
yielded pure product 4c (0.25 g; 82%) as a colorless syrup, [α]D –4.2° (c 2.8). 1H NMR spectrum:
1.29 d, 3 H, J(5,6) = 6.7 (Me-5); 2.15 ddd, 1 H, J(3a,3b) = 14, J(2,3a) = 3.7, J(3a,4) = 3.6 (H-3a);
2.61 ddd, 1 H, J(2,3b) = 7, J(3a,3b) = 14, J(3b,4) = 6.8 (H-3b); 3.86–4.07 m, 4 H (dioxolane CH2);
4.13 ddd, 1 H, J(1,2) = 5.4, J(2,3a) = 3.7, J(2,3b) = 7 (H-2); 4.36 m, 1 H (H-5); 5.0 d, 1 H, J(1,2) = 5.4
(H-1); 5.15 ddd, 1 H, J(3a,4) = 3.6, J(3b,4) = 6.8, J(4,5) = 3.7 (H-4); 7.30–8.10 m, 5 H (ArH). 13C NMR
spectrum: 18.64 (C-6), 32.57 (C-3), 65.23 and 65.4 (dioxolane CH2), 77.95 (C-2), 79.34 (C-4), 80.02
(C-5), 104.59 (C-1), 128.36, 129.58, 129.75 and 133.11 (ArC), 166.1 (C=O).
This work was supported by the Ministry of Science and Technology of the Republic of Serbia. The
authors thank Dr P. Radivojsa, Faculty of Chemistry, University of Belgrade, for the optical rotation
measurements.
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