Synthesis of (1R,2S)- and (1S,2S)-3-azido-1,2-dihydroxypropylphosphonates

Article abstract of DOI:10.1016/S0957-4166(02)00223-9

An efficient synthesis of diastereomerically pure dimethyl (1R,2S)- and (1S,2S)-3-azido-1,2-dihydroxypropylphosphonates from L-ascorbic acid, via new chirons: (2S,3S)-4-azido-3-benzyloxy-1,2-O-isopropylidene-1,2-butanediol and (2S)-3-azido-2-benzyloxypropanal was elaborated.

Full text of DOI:10.1016/S0957-4166(02)00223-9

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 989–994
Synthesis of (1R,2S)- and
(1S,2S)-3-azido-1,2-dihydroxypropylphosphonates
Andrzej E. Wro´blewski* and Iwona E. Głowacka
Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Ło´dz´, 90-151 Ło´dz´, Muszyn´skiego 1, Poland
Received 24 April 2002; accepted 4 May 2002
Abstract—An efficient synthesis of diastereomerically pure dimethyl (1R,2S)- and (1S,2S)-3-azido-1,2-dihydroxypropylphospho-
nates from
L-ascorbic acid, via new chirons: (2S,3S)-4-azido-3-benzyloxy-1,2-O-isopropylidene-1,2-butanediol and (2S)-3-azido-2-
benzyloxypropanal was elaborated. © 2002 Published by Elsevier Science Ltd.
1. Introduction
phites.12 These achievements have stimulated our inter-
est in the synthesis of 3-amino-1,2-dihydroxypro-
Of the various aminoalkylphosphonates, a-amino
derivatives form the most prominent subclass because
they serve as analogues of a-aminoacids.1 Alkylphos-
phonates bearing an amino group in the b or g posi-
tions are less known, although b-aminoethylphosphonic
acid (ciliatine) was the first aminophosphonate found in
nature.2 Phosphoalanine3 and 2-amino-1-hydroxy-
ethylphosphonic acid4 are other examples of b-
aminophosphonates isolated from natural sources.
Fosfidomycin and structurally related g-aminophospho-
nates are active as antibiotics.5–8 Additionally, a num-
ber of g- and d-aminophosphonates have been
synthesised and their ability as ligands for glutamate
receptors has been investigated.9
pylphosphonates of the type 1. To secure the 2R
configuration in 1, 2,3-O-cyclohexylidene-
D
-glyceralde-
starting material, and
trihydroxypropylphosphonates
hyde was selected as
diastereoisomeric
a
obtained in the Abramov reaction13 were transformed
into stereochemically homogeneous 2,3-epoxy-1-benzyl-
oxypropylphosphonates as precursors to (2R)-1
(Scheme 1).14
For some time we have been involved in stereochemical
studies on b-aminoalkylphosphonates. Enantiomeric N-
substituted 2-amino-1-hydroxy-2-phenylethylphospho-
nates have recently been synthesised as phosphonate
analogues of paclitaxel and docetaxel C-13 side
chains.10,11 Highly enantiomerically enriched substi-
tuted 2-amino-1,3-dihydroxypropylphosphonates were
obtained from Garner aldehyde and dialkyl phos-
Scheme 1. Retrosynthesis of (2R)-1.
In order to synthesise the phosphonates (2S)-1 we
turned to
L
-ascorbic acid 2 as a source of chirality
(Scheme 2).15
Herein, we describe the transformation of 2 into a new
four-carbon chiron, (2S,3S)-4-azido-3-benzyloxy-1,2-
Scheme 2. Retrosynthesis of (2S)-1.
* Corresponding author. Fax: 48-42-678-83-98; e-mail: aewplld@ich.pharm.am.lodz.pl
0957-4166/02/$ - see front matter © 2002 Published by Elsevier Science Ltd.
PII: S0957-4166(02)00223-9

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A. E. Wro´blewski, I. E. Głowacka / Tetrahedron: Asymmetry 13 (2002) 989–994
O-isopropylidene-1,2-butanediol 3, one-step deiso-
propylidenation–periodate oxidation of 3 to (2S)-3-
Pd(OH)2/C as catalysts. We found that hydrogenation
of the azido group is much faster than hydrogenolysis
of the benzyl group, which takes 1 week for completion
irrespective of the catalyst used.
azido-2-benzyloxypropanal
4 and the addition of
dialkyl phosphites to 4 to afford diastereoisomeric 3-
azidoalkylphosphonates 9 and 10.
To assign the absolute configurations at C(1) in 9a and
9b, the diols 12a and 12b were reacted with 2,2-
dimethoxypropane to form substituted 1,3-dioxolanes
13a and 13b, respectively (Scheme 5). Analysis of vici-
nal coupling constants (H(4)–H(5) 9.1 Hz, H(5)–P 10.8
Hz, P–C(4)–C(5)–C 0 Hz and P–C(4)–O(3)–C(2) 10.4
Hz) strongly supports the existence of 13a in a single E4
conformation, in which the O,O-dimethylphosphoryl
group is equatorial, while the acetamidomethyl group
occupies pseudoequatorial position (Scheme 6). On the
other hand, the 1,3-dioxolane 13b exists in the E1
conformation having the largest substituents positioned
pseudoequatorially. Again, a set of vicinal couplings
(H(4)–H(5) 6.9 Hz, H(5)–P 23.2 Hz, P–C(4)–C(5)–C 4.8
Hz and P–C(4)–O(3)–C(2) 6.3 Hz)24–31 is in a full
agreement with the proposed conformation. Based on
the results of the conformational studies on 13a and
13b, it was concluded that the absolute configurations
at C(1) in 9a and 9b are 1S and 1R, respectively.
2. Results and discussion
The protected a-hydroxy ester 5 was prepared accord-
ing to the literature procedure16 in 78% overall yield.
After O-benzylation of 5 the known compound 6 was
obtained (Scheme 3).17 It was reduced with NaBH4–
LiCl mixture18 to produce (2S,3S)-2-O-benzyl-3,4-O-
isopropylidenebutanetetrol 7 in 90% yield. Alternative
procedures for preparation of 7 employ L-tartrates as a
source of chirality and LiAlH4 as a reducing agent.19–21
Quantitative mesylation of 7 led to the mesylate 8,22
which after azidation gave unknown (2S,3S)-4-azido-3-
benzyloxy-1,2-O-isopropylidene-1,2-butanediol
3
in
35% overall yield from -ascorbic acid. The synthesis of
L
the aldehyde 4 from the 1,2-O-isopropylidene derivative
3 was accomplished with periodic acid in AcOEt.23
However, the aldehyde 4 appeared to be very unstable
and after removal of inorganic impurities by filtration
through a pad of silica gel it was used immediately in
the next step.
Before we decided to employ isopropylidene derivatives
13a and 13b for configurational assignments of 9a and
9b, conformational analysis of acyclic systems in the
diastereoisomeric azides 9 and acetamides 12 was per-
formed. It was noticed that the O,O-dimethylphospho-
ryl and azidomethyl groups in 9 prefer antiperiplanar
arrangements, but because of significant contributions
from the gauche conformers, reliable configurational
conclusions could not be drawn. Although diastereoiso-
The crude aldehyde 4 was reacted separately with
dimethyl and diethyl phosphites in the presence of NEt3
as a catalyst to give phosphonates 9a/9b and 10a/10b in
ca. 1:1 ratios (Scheme 4). The diastereoselectivity of the
addition remained unchanged using Ti(Oi-Pr)4 as a
catalyst or when dimethyl trimethylsilyl phosphite was
applied. Separation of the diastereoisomeric phospho-
nates was readily achieved for the methyl esters only to
afford less polar 9a as white needles (43%) and the
more polar 9b as a colorless oil (42%).
Finally, the g-azidophosphonates 9a and 9b were trans-
formed into 3-acetamido-1,2-dihydroxypropylphospho-
nates 12a and 12b, respectively, as shown in Scheme 5.
After quantitative acetylation of the C(1) hydroxyl
group, the acetates 11a and 11b were subjected to
hydrogenation under atmospheric pressure at room
temperature in the presence of 10% Pd/C or 20%
Scheme 4. Synthesis of the diastereoisomeric phosphonates 9
and 10. Reagents and conditions: (a) (RO)2P(O)H, NEt3, rt.
Scheme 3. Synthesis of the aldehyde 4. Reagents and conditions: (a) BnBr, Ag2O; (b) NaBH4, LiCl; (c) MsCl, pyridine, CH2Cl2;
(d) NaN3, DMF, 60°C; (e) H5IO6.

A. E. Wro´blewski, I. E. Głowacka / Tetrahedron: Asymmetry 13 (2002) 989–994
991
Scheme 5. Synthesis of diastereoisomeric 3-amino-1,2-dihydroxypropylphosphonates. Reagents and conditions: (a) Ac2O, NEt3,
DMAP; (b) H2, Pd–C; (c) Me2C(OMe)2, TosOH.
methanol (100:1, v/v) to give 6 as a colorless oil (1.757
g, 72%). IR (film): w=2998, 1744, 1372, 1210, 1074
1
cm−1; H NMR (300 MHz, CDCl3): l=7.40–7.26 (m,
5H), 4.79 and 4.51 (AB, J=11.9 Hz, 2H), 4.40 (dddꢀq,
J=6.5 Hz, J=6.5 Hz, J=5.6 Hz, 1H), 4.01 (dAB,
J=8.7 Hz, J=6.5 Hz, 1H), 4.00 (d, J=5.6 Hz, 1H),
3.97 (dAB, J=8.7 Hz, J=6.5 Hz, 1H), 3.77 (s, 3H),
1.40 (s, 3H), 1.35 (s, 3H); 13C NMR (75.5 MHz,
CDCl3): l=170.43, 136.92, 128.34, 128.09, 127.94,
109.85, 78.34, 75.85, 72.83, 65.49, 52.16, 26.36, 25.40.
Scheme 6. Preferred conformations of 1,3-dioxolanes 13a and
13b.
4.2. (2S,3S)-3-Benzyloxy-1,2-O-isopropylidene-1,2,4-
meric acetamides 12 exist predominantly as anti-con-
formers (3JP–C3=13.2 and 13.6 Hz)30–32 and spatial
relationships of H(1) and H(2) in 12a and 12b are
gauche (2.7 Hz) and anti (9.8 Hz), respectively, signal
overlaps prohibited extraction of stereochemically rele-
vant vicinal P–H(2) couplings, thus making configura-
tional assignments at C(1) doubtful.
butanetriol 7
To a cooled (0°C) solution of 6 (1.435 g, 5.12 mmol) in
THF–EtOH (22 mL, 1:2, v/v), LiCl (0.651 g, 15.4
mmol) and NaBH4 (0.581 g, 15.4 mmol) were added.
The reaction mixture was allowed to warm to room
temperature and was stirred for 20 h. After quenching
with acetone (6 mL), chloroform (30 mL) was added
followed by MgSO4 (5 g). The mixture was filtered and
the filtrate was concentrated in vacuo. The residue was
purified on a silica gel column with chloroform–
methanol (100:1, v/v) to afford 7 as a colorless oil
(1.161 g, 90%). IR (film): w=3410, 2934, 2882, 1455,
3. Conclusions
An efficient synthesis of a four-carbon chiron, (2S,3S)-
4-azido-3-benzyloxy-1,2-O-isopropylidene-1,2-butane-
diol, was elaborated starting from
L-ascorbic acid.
1
1372, 1214, 1057 cm−1; H NMR (300 MHz, CDCl3):
Using a one-pot procedure it was transformed into
unstable (2S)-3-azido-2-benzyloxypropanal, which was
readily phosphonylated with dialkyl phosphites.
l=7.38–7.25 (m, 5H), 4.77 and 4.69 (AB, J=11.7 Hz,
2H), 4.31 (ddd, J=6.9 Hz, J=6.5 Hz, J=6.0 Hz, 1H),
4.01 (dd, J=8.3 Hz, J=6.5 Hz, 1H), 3.82 (dd, J=8.3
Hz, J=6.9 Hz, 1H), 3.78–3.69 (m, 1H), 3.64–3.54 (m,
2H), 1.44 (s, 3H), 1.37 (s, 3H).
4. Experimental
General procedures and instrumentation have been
4.3. Mesylation of 7
1
described earlier.14 In addition, some H, 13C and 31P
NMR spectra were obtained on a Varian-Mercury
spectrometer at 300, 75.5 and 121.5 MHz, respectively.
To a solution of 7 (1.16 g, 4.60 mmol) and pyridine (1.2
mL) in CH2Cl2 (6 mL) mesyl chloride (0.47 mL, 6.0
mmol) was added dropwise at 0°C and the reaction
mixture was left at room temperature for 20 h. After
diluting with CH2Cl2 (15 mL), the solution was washed
with water (20 mL). The aqueous phase was extracted
with CH2Cl2 (3×20 mL) and organic phases were dried
(MgSO4) and concentrated. The residue was coevapo-
rated with toluene (3×20 mL) and finally kept in vacuo
for 8 h to afford the crude mesylate 8 as a pale yellow
4.1. Methyl (2R,3S)-2-benzyloxy-3,4-O-isopropylidene-
3,4-dihydroxybutanoate 6
A suspension of 5 (1.67 g, 8.78 mmol), benzyl bromide
(1.62 mL, 14.05 mmol), Ag2O (3.26 g, 14.1 mmol) and
powdered molecular sieves was stirred at room temper-
ature for 4 h. After filtration through a pad of Celite,
the solvent was evaporated and the crude product was
purified on a silica gel column with chloroform–
1
oil (1.504 g, 99%). H NMR (300 MHz, CDCl3): l=
7.37–7.26 (m, 5H), 4.74 and 4.70 (AB, J=11.9 Hz, 2H),

992
A. E. Wro´blewski, I. E. Głowacka / Tetrahedron: Asymmetry 13 (2002) 989–994
4.39 (dAB, J=10.9 Hz, J=3.8 Hz, 1H), 4.27 (dt, J=5.2
Hz, J=6.5 Hz, 1H), 4.26 (dAB, J=10.9 Hz, J=6.1 Hz,
1H), 4.02 (dd, J=8.5 Hz, J=6.7 Hz, 1H), 3.83 (dd,
J=8.5 Hz, J=6.5 Hz, 1H), 3.76 (ddd, J=6.2 Hz,
J=5.2 Hz, J=3.8 Hz, 1H), 2.99 (s, 3H), 1.43 (s, 3H),
1.35 (s, 3H).
838, 756, 700 cm−1; 1H NMR (300 MHz, CDCl3):
l=7.41–7.31 (m, 5H), 4.75 (s, 2H), 4.01 (dAB, JAB
=
3.6 Hz, J=10.1 Hz, 1H, H-1), 3.96 (dddAB, J=3.6 Hz,
J=5.8 Hz, J=5.8 Hz, J=9.3 Hz, 1H, H-2), 3.810 and
3.806 (2d, J=10.7 Hz, 6H), 3.524 and 3.517 (AB part
of ABX system, JAB=12.6 Hz, J=5.8 Hz, J=5.8 Hz,
2H), 2.8–1.8 (brs, 1H); 13C NMR (75.5 MHz, CDCl3):
l=137.27, 128.53, 128.34, 128.17, 77.13 (d, J=3.4 Hz),
73.91, 67.92 (d, J=162.0 Hz), 53.81 (d, J=8.0 Hz),
53.32 (d, J=6.9 Hz), 51.19 (d, J=10.3 Hz); 31P NMR
(121.5 MHz, CDCl3): l=24.40. Anal. calcd for
C12H18N3O5P: C, 45.72; H, 5.75; N, 13.33. Found: C,
45.76; H, 5.54; N, 13.14%.
4.4. (2S,3S)-4-Azido-3-benzyloxy-1,2-O-isopropylidene-
1,2-butanediol 3
A mixture of 8 (1.504 g, 4.55 mmol) and NaN3 (0.355
g, 5.46 mmol) in DMF (5 mL) was heated at 60°C for
48 h. After diluting with AcOEt (15 mL), the precipi-
tate was filtered off, and the organic phase was washed
with aqueous NaHCO3 (5%, 2×20 mL) and brine (2×30
mL), dried with MgSO4 and concentrated. The residue
was chromatographed on a silica gel column with chlo-
roform–methanol (100:1, v/v) to afford 3 as a colorless
oil (1.016 g, 81%). [h]D=+10.5 (c=2.47 in CHCl3). IR
4.6.2. Dimethyl (1R,2S)-3-azido-2-benzyloxy-1-hydroxy-
propylphosphonate 9b. Colorless oil. [h]D=+23.4 (c=
1.02 in CHCl3). IR (film): w=3274, 2956, 2855, 2103,
1
1224, 1053, 836, 743, 699 cm−1; H NMR (300 MHz,
1
CDCl3): l=7.41–7.26 (m, 5H), 4.72 and 4.66 (AB,
(film): w=2987, 2935, 2886, 2102, 1214, 1074 cm−1; H
J
AB=11.1 Hz, 2H), 4.14 (dd, J=7.5 Hz, J=6.3 Hz,
NMR (300 MHz, CDCl3): l=7.40–7.26 (m, 5H), 4.75
and 4.72 (AB, J=11.7 Hz, 2H), 4.26 (dddꢀq, J=6.8
Hz, J=6.6 Hz, J=5.6 Hz, 1H), 3.99 (dAB, J=8.6 Hz,
J=6.6 Hz, 1H), 3.79 (dAB, J=8.6 Hz, J=6.8 Hz, 1H),
3.64 (ddd, J=6.5 Hz, J=5.6 Hz, J=4.4 Hz, 1H), 3.37
(dAB, J=13.1 Hz, J=4.2 Hz, 1H), 3.33 (dAB, J=13.1
Hz, J=6.5 Hz, 1H), 1.43 (s, 3H), 1.35 (s, 3H); 13C
NMR (75.5 MHz, CDCl3): l=137.76, 128.34, 127.87,
127.79, 109.45, 78.36, 75.84, 73.22, 65.31, 51.32, 26.44,
25.23. Anal. calcd for C14H19N3O3: C, 60.63; H, 6.90;
N, 15.15. Found: C, 60.71; H, 6.80; N, 15.28%.
1H), 3.90 (dddd, J=9.7 Hz, J=6.3 Hz, J=5.6 Hz,
J=3.4 Hz, 1H), 3.78 and 3.75 (2×d, J=10.6 Hz, 6H),
3.61 and 3.60 (AB part of ABX system, JAB=13.5 Hz,
J=5.6 Hz, J=3.4 Hz, 2H), 3.4–1.8 (brs, 1H); 13C NMR
(75.5 MHz, CDCl3): l=137.36, 128.55, 128.31, 128.13,
78.38 (d, J=4.0 Hz), 73.14, 67.59 (d, J=160.6 Hz),
58.68 and 58.67 (2d, J=6.0 Hz), 51.33 (d, J=8.0 Hz);
31P NMR (121.5 MHz, CDCl3): l=26.14. Anal. calcd
for C12H18N3O5P: C, 45.72; H, 5.75; N, 13.33. Found:
C, 45.51; H, 5.91; N, 13.07%.
4.5. (2S)-3-Azido-2-benzyloxypropanal 4
4.7. Dimethyl 3-acetamido-1,2-dihydroxypropylphospho-
nates 12
A solution of 3 (0.932 g, 3.36 mmol) and H5IO6 (0.843
g, 3.70 mmol) in AcOEt (6 mL) was stirred at room
temperature for 1 h. The reaction mixture was filtered
through a pad of silica gel and the solution was concen-
trated to give unstable 4 as a yellowish oil (0.642 g,
4.7.1. Acetylation of 9a and 9b, general procedure. A
solution of 9 (1.0 mmol), Ac2O (3.0 mmol) and NEt3
(3.3 mmol) in CH2Cl2 (1 mL) containing a few crystals
of DMAP was stirred at room temperature for 0.5 h.
The reaction mixture was diluted with CH2Cl2 (20 mL),
washed with H2O (2×20 mL), aqueous NaHCO3 (25
mL), dried over MgSO4 and concentrated. The crude
product was purified on a silica gel column with chloro-
form–methanol–triethylamine (100:1:0.1, v/v).
1
93%). H NMR (300 MHz, CDCl3): l=9.69 (d, J=1.0
Hz, 1H), 7.40–7.30 (m, 5H), 4.76 (s, 2H), 3.96 (ddd,
J=5.7 Hz, J=4.2 Hz, J=1.0 Hz, 1H), 3.55 (dAB,
J=12.3 Hz, J=4.2 Hz, 1H), 3.52 (dAB, J=12.3 Hz,
J=5.7 Hz, 1H).
4.6. Addition of dimethyl phosphite to (2S)-4
Compound (1S,2S)-11a: From (1S,2S)-9a (0.109 g,
0.360 mmol), (1S,2S)-11a (0.113 g, 92%) was obtained
as a colorless oil. [h]D=−2.9 (c=1.75 in CHCl3). IR
(film): w=2956, 2930, 2857, 2104, 1753, 1219, 1030
A mixture of the crude aldehyde (2S)-4 (0.303 g, 1.48
mmol), dimethyl phosphite (0.168 mL, 1.48 mmol) and
triethylamine (0.021 mL, 0.15 mmol) was stirred at
room temperature for 20 h. After addition of CH2Cl2
(10 mL), the solution was washed with water (2×20
mL), dried over MgSO4 and concentrated to leave a
yellowish oil, which was chromatographed on a silica
gel column with a chloroform–methanol–triethylamine
mixture (100:1:0.2, v/v). The appropriate fractions were
collected to give: 9a (0.184 g, 43%), a mixture of 9a and
9b (0.053 g, 12%) and 9b (0.180 g, 42%).
1
cm−1; H NMR (300 MHz, CDCl3): l=7.39–7.27 (m,
5H), 5.50 (dd, J=11.1 Hz, J=5.8 Hz, 1H), 4.73 (s, 2H),
3.99 (dddd, J=9.2 Hz, J=6.0 Hz, J=5.8 Hz, J=4.8
Hz, 1H), 3.78 and 3.77 (2×d, J=10.8 Hz, 6H), 3.50
(dAB, JAB=13.0 Hz, J=6.0 Hz, 1H), 3.46 (dAB, JAB
=
13.0 Hz, J=4.8 Hz, 1H), 2.12 (s, 3H); 13C NMR (75.5
MHz, CDCl3): l=169.30 (d, J=4.9 Hz), 137.24,
128.50, 128.14, 128.09, 76.79 (d, J=3.8 Hz), 67.36 (d,
J=164.6 Hz), 53.74 (d, J=6.8 Hz), 53.54 (d, J=6.0
Hz), 51.62 (d, J=6.3 Hz), 20.79; 31P NMR (121.5
MHz, CDCl3): l=20.78. Anal. calcd for C14H20N3O6P:
C, 47.06; H, 5.64; N, 11.76. Found: C, 46.80; H, 5.52;
N, 11.69%.
4.6.1. Dimethyl (1S,2S)-3-azido-2-benzyloxy-1-hydroxy-
propylphosphonate 9a. White needles. Mp 71–72°C
(from diethyl ether). [h]D=+16.6 (c=2.19 in CHCl3).
IR (KBr): w=3214, 2956, 2863, 2163, 2096, 1241, 1064,

A. E. Wro´blewski, I. E. Głowacka / Tetrahedron: Asymmetry 13 (2002) 989–994
993
Compound (1R,2S)-11b: From (1R,2S)-9b (0.095 g, 0.30
4.8. Dimethyl 1,2-O-isopropylidene-3-acetamido-1,2-
mmol), (1R,2S)-11b was obtained as a colorless oil
(0.090 g, 81%). [h]D=+2.0 (c=1.38 in CHCl3). IR
dihydroxypropylphos-phonates 13, general procedure
1
(film): w=2956, 2854, 2101, 1753, 1216, 1028 cm−1; H
A solution of the diol 12 (1.0 mmol) and 2,2-
dimethoxypropane (2.0 mmol) in CH2Cl2 (1 mL) con-
taining a few crystals of p-toluenesulfonic acid was left
at room temperature for 4.5 h. The catalyst was neu-
tralized with NEt3 (0.2 mL) and the volatiles were
removed in vacuo. The crude products were purified on
a silica gel column with chloroform–methanol–triethy-
lamine (50:1:0.1, v/v).
NMR (300 MHz, CDCl3): l=7.41–7.29 (m, 5H), 5.63
(dd, J=12.93 Hz, J=3.8 Hz, 1H), 4.73 and 4.62 (AB,
JAB=11.1 Hz, 2H), 3.98 (dddd, J=7.9 Hz, J=7.1 Hz,
J=3.8 Hz, J=3.6 Hz, 1H), 3.78 and 3.75 (2×d, J=10.7
Hz, 6H), 3.55 (dAB, JAB=13.3 Hz, J=3.6 Hz, 1H),
3.51 (dAB, JAB=13.3 Hz, J=7.1 Hz, 1H), 2.15 (s, 3H);
13C NMR (75.5 MHz, CDCl3): l=169.12 (d, J=4.9
Hz), 136.84, 128.49, 128.43, 128.12, 77.15, 72.72, 66.37
(d, J=164.6 Hz), 53.75 (d, J=7.2 Hz), 53.47 (d, J=
6.7), 51.30 (d, J=2.9 Hz), 20.77; 31P NMR (121.5
MHz, CDCl3): l=20.67. Anal. calcd for C14H20N3O6P:
C, 47.06; H, 5.64; N, 11.76. Found: C, 47.25; H, 5.36;
N, 11.58%.
Compound (1S,2S)-13a: From (1S,2S)-12a (0.054 g,
0.21 mmol), (1S,2S)-13a (0.049 g, 78%) was obtained as
a colorless oil. [h]D=−2.0 (c=0.98 in CHCl3); IR (film):
w=3438, 3297, 2990, 2960, 2939, 2856, 1659, 1555,
1
1248, 1043 cm−1; H NMR (300 MHz, CDCl3): l=6.4
(brs, 1H), 4.34 (dddd, J=10.8 Hz, J=9.1 Hz, J=5.2
Hz, J=5.2 Hz, 1H), 3.91 (dd, J=9.1 Hz, J=2.4 Hz,
1H), 3.87 and 3.86 (2×d, J=10.7 Hz, 6H), 3.68 (ddAB,
4.7.2. Hydrogenolysis of azides 11a and 11b, general
procedure. A solution of the azide (0.3 mmol) in
methanol (0.5 mL) was kept under a hydrogen atmo-
sphere over Pd/C catalyst (5 mg) at room temperature
for 7 days. The suspension was filtered through a pad
of Celite and washed with methanol. After evaporation
of the solvent, the residue was chromatographed on a
silica gel column with chloroform–methanol (10:1, v/v).
J
AB=13.9 Hz, J=6.7 Hz, J=5.2 Hz, 1H), 3.46 (ddAB,
AB=13.9 Hz, J=5.2 Hz, J=5.2 Hz, 1H), 2.01 (s, 3H),
J
1.46 (s, 3H), 1.44 (s, 3H); 13C NMR (62.9 MHz,
CDCl3): l=170.30, 111.41 (d, J=10.4 Hz), 75.93 (d,
J=5.0 Hz), 73.38 (d, J=172.2 Hz), 53.87 (d, J=7.0
Hz), 53.55 (d, J=6.7 Hz), 40.79, 26.57, 25.91, 23.06; 31
P
NMR (121.5 MHz, CDCl3): l=22.30. Anal. calcd for
C10H20NO6P: C, 42.71; H, 7.17; N, 4.98. Found: C,
42.42; H, 7.19; N, 4.74%.
Compound (1S,2S)-12a: From (1S,2S)-11a (0.113 g,
0.32 mmol) in the presence of 10% Pd–C, (1S,2S)-12a
(0.061 g, 86%) was obtained as a colorless oil. [h]D=
−12.4 (c=2.12 in CHCl3). IR (film): w=3297, 2959,
2856, 1654, 1558, 1219, 1048 cm−1; 1H NMR (300
MHz, CDCl3): l=6.73 (brt, 1H), 4.54 (brdd, J=11.0
Hz, J=7.1 Hz, 1H, HO-C1), 4.40 (brd, J=5.4 Hz, 1H,
HO-C2), 4.06–3.98 (m, 1H, H-2), 3.93 (ddd, J=11.7
Hz, J=7.1 Hz, J=2.7 Hz, 1H, H-1), 3.86 and 3.82 (2d,
J=10.5 Hz, 6H), 3.61 (ddAB, JAB=14.1 Hz, J=7.0
Hz, J=6.0 Hz, 1H, H-3a), 3.68 (ddAB, JAB=14.1 Hz,
J=7.2 Hz, J=5.6 Hz, 1H, H-3b), 2.04 (s, 3H); 13C
NMR (75.5 MHz, CDCl3): l=172.31, 69.67 (d, J=1.5
Hz, C-2), 68.72 (d, J=164.3 Hz, C1), 54.14 and 53.34
(2d, J=7.0 Hz), 42.39 (d, J=13.2 Hz, C-3), 23.15; 31P
NMR (121.5 MHz, CDCl3): l=25.67. Anal. calcd for:
C7H18NO7P: C, 32.44; H, 7.00; N, 5.38. Found: C,
32.68; H, 7.29; N, 5.57%.
Compound (1R,2S)-13b: From (1R,2S)-12b (0.051 g,
0.18 mmol), (1R,2S)-13b (0.048 g, 63%) was obtained
as a colorless oil. [h]D=+31.3 (c=0.97 in CHCl3); IR
(film): w=3407, 3300, 2989, 2959, 2856, 1659, 1552,
1
1224, 1040 cm−1; H NMR (300 MHz, CDCl3): l=6.66
(brs, 1H), 4.48 (dddd, J=23.2 Hz, J=6.9 Hz, J=6.9
Hz, J=6.1 Hz, 1H), 4.37 (dd, J=6.9 Hz, J=1.0 Hz,
1H), 3.88 and 3.84 (2×d, J=10.6 Hz, 6H), 3.80 (ddd,
J=13.9 Hz, J=6.4 Hz, J=6.1 Hz, 1H), 3.57 (ddd,
J=13.9 Hz, J=6.9 Hz, J=6.6 Hz, 1H), 2.00 (s, 3H),
1.53 (s, 3H), 1.35 (s, 3H); 13C NMR (75.5 MHz,
CDCl3): l=170.36, 110.95 (d, J=6.3 Hz), 75.45, 72.73
(d, J=169.9 Hz), 53.98 (d, J=7.1 Hz), 53.41 (d, J=7.2
Hz), 39.74 (d, J=4.8 Hz), 26.91, 25.08, 23.59; 31P NMR
(121.5 MHz, CDCl3): l=22.32. Anal. calcd for
C10H20NO6P: C, 42.71; H, 7.17; N, 4.98. Found: C,
42.55; H, 7.46; N, 4.83%.
Compound (1R,2S)-12b: From (1R,2S)-11b (0.137 g,
0.38 mmol) in the presence of 20% Pd(OH)2/C,
(1R,2S)-12b (0.085 g, 82%) was obtained as a colorless
oil. [h]D=+35.6 (c=1.81 in CHCl3); IR (film): w=3307,
Acknowledgements
1
2959, 2856, 1647, 1556, 1226, 1054 cm−1; H NMR (300
MHz, CDCl3): l=6.61 (brm, 1H), 5.49 (dd, J=25.5
Hz, J=5.4 Hz, 1H, HO-C1), 4.36 (brs, 1H, HO-C2),
4.02–3.82 (m, 2H, H-2, H-3a), 3.89 and 3.86 (2d, J=
10.6 Hz, 6H), 3.67 (ddd, J=9.8 Hz, J=9.8 Hz, J=5.4
Hz, 1H, H-1), 3.24 (dddd, J=14.7 Hz, J=5.0 Hz,
J=3.0 Hz, J=3.0 Hz, 1H, H-3b), 2.08 (s, 3H); 13C
NMR (75.5 MHz, CDCl3): l=173.37, 70.52 (d, J=2.9
Hz, C-2), 67.59 (d, J=164.6 Hz, C-1), 54.20 and 53.81
(2d, J=6.8 Hz), 41.68 (d, J=13.6 Hz, C-3), 23.07; 31P
NMR (121.5 MHz, CDCl3): l=27.58. Anal. calcd for
C7H18NO7P: C, 32.44; H, 7.00; N, 5.40. Found: C,
32.24; H, 7.06; N, 5.38%.
Financial support from the Medical University of Ło´dz´
(502-13-853) is gratefully acknowledged.
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