SPECIAL TOPIC
Synthesis of myo- and chiro-Inositols from D-Xylose
3153
7a
13C NMR (CDCl3): d = 139.4, 138.9, 138.6, 138.5, 135.8, 128.5,
128.3, 128.27, 128.2, 128.1, 128.0, 127.6, 127.3, 118.7, 116.0, 84.2,
82.0, 81.4, 77.4, 75.9, 75.0, 70.8, 18.3, 12.5.
HRMS (ESI): m/z calcd for C38H52O4Si + Na (M + Na)+: 623.3533;
found: 623.3522.
[a]D25 –18.2 (c 1.0, CHCl3).
1H NMR (300 MHz, CDCl3): d = 7.35–7.15 (m, 15 H), 4.95 (d,
J = 11.4 Hz, 1 H), 4.83 (d, J = 10.7 Hz, 1 H), 4.74–4.64 (m, 4 H),
4.17 (m, 1 H), 4.11 (yt, J = 8.8 Hz, 1 H), 3.94 (yt, J = 8.8 Hz, 1 H),
3.53 (dd, J = 8.8, 2.9 Hz, 1 H), 3.42 (m, 1 H), 3.33 (yt, J = 8.8 Hz,
1 H), 2.54 (br s, 1 H), 2.48 (br d, 1 H).
13C NMR (CDCl3): d = 138.9, 138.4, 137.7, 128.4, 128.2, 128.0,
127.8, 126.8, 79.0, 78.7, 78.5, 78.1, 77.9, 76.1, 75.7, 75.4, 18.2,
18.1, 13.1.
(3S,4S,5R)-Tribenzyloxy-(2S)-triisopropylsilyloxy-1,6-hexane-
dial (13)
A solution of 12 (65 mg, 0.11 mmol) in pyridine (20 mL) and
CH2Cl2 (2 mL) was cooled to –78 °C and subjected to a flow of O3
in dry O2 (0.05 CFM). When TLC indicated the complete disappear-
ance (about 5 min) of 12 [hexane–EtOAc, 9:1, Rf (12) = 0.6], Me2S
(0.2 mL) was added. The mixture was allowed to warm to 20 °C and
kept for 1 h, after which it was treated with H2O (1.5 mL) and the
layers were separated. The aqueous phase was reextracted with
CH2Cl2 (2 × 2 ML), the combined CH2Cl2 layers were dried
(MgSO4), and evaporated to produce crude 13. This residue was
used directly in the next reaction.
1H NMR (300 MHz, CDCl3): d = 9.68 (s, 1 H), 9.63 (s, 1 H), 7.40–
7.15 (m, 15 H), 4.75 (d, J = 12 Hz, 2 H), 4.58 (s, 2 H), 4.51 (d,
J = 12.0 Hz, 1 H), 4.48 (d, J = 12.0 Hz, 1 H), 4.25 (s, 1 H), 4.12–
4.05 (m, 2 H), 3.95 (yt, J = 5 Hz, 1 H), 1.04 (m, 21 H).
FAB-HRMS (NBA/NaI): m/z calcd for C36H50O6Si + Na (M + Na)+:
629.3276; found: 629.3272.
8a
[a]D25 –20.4 (c 1.0, CHCl3).
1H NMR (300 MHz, CDCl3): d = 7.37–7.15 (m, 15 H), 4.95 (d,
J = 12 Hz, 1 H), 4.88 (d, J = 12 Hz, 1 H), 4.84 (d, J = 12 Hz, 1 H),
4.82 (s, 2 H), 4.78 (d, J = 12 Hz, 1 H), 4.10 (m, 1 H), 3.88–3.75 (m,
3 H), 3.53 (br d, J = 10 Hz, 1 H), 3.46 (yt, J = 10 Hz, 1 H), 2.55 (br
s, 1 H), 2.41 (br s, 1 H).
13C NMR (CDCl3): d = 138.9, 138.6, 138.4, 128.5, 128.3, 128.1,
127.9, 127.7, 127.0, 79.1, 78.8, 78.5, 78.2, 77.9, 76.1, 75.8, 75.5,
18.1, 12.7.
2,3,4-Tri-O-benzyl-1-O-triisopropylsilyl-L-chiro-inositol (14)
The crude dialdehyde 13 from above was diluted with t-BuOH
(30 mL, 0.3 mmol) in THF (6 mL) and added dropwise to a cold
(–78 °C) solution of SmI2 (0.6 mmol) in THF (6 mL). The mixture
was stirred at –78 °C for 3 h and then overnight at 20 °C. Aq sat.
NaHCO3 (6 mL) was added and the white slurry was extracted with
EtOAc (2 × 10 mL). The combined organic layers were washed
with aq 10% Na2S2O3, brine, and dried (MgSO4). Evaporation of the
solvent and flash chromatography (hexane–EtOAc, 8:2) afforded
14 (38 mg, 58%) followed by an unidentified isomeric diol (3 mg);
[a]D25 –39.0 (c 1.0, CHCl3).
1H NMR (300 MHz, CDCl3): d = 7.38–7.26 (m, 15 H), 5.01 (d,
J = 11.5 Hz, 1 H), 4.97 (d, J = 10.8 Hz, 1 H), 4.81 (d, J = 10.8 Hz,
1 H), 4.77 (d, J = 11.4 Hz, 1 H), 4.70 (d, J = 11.5 Hz, 1 H), 4.64 (d,
J = 11.4 Hz, 1 H), 4.31 (dd, J = 3.8, 2.7 Hz, 1 H), 4.02–3.89 (m, 3
H), 3.80 (dd, J = 9.8, 2.7 Hz, 1 H), 3.63 (yt, J = 9.3 Hz, 1 H), 2.3 (br
s, 1 H), 1.65 (br s, 1 H), 1.02 (m, 21 H).
HRMS (ESI): m/z calcd for C36H51O6Si (M + H)+: 607.3449; found:
607.3463.
3,4,5-Tri-O-benzyl-D-myo-inositol (7i)
To a solution of 7a (4.0 mg) in THF (0.5 mL) was added 1 M Bu4NF
in THF (0.1 mL, containing 5% H2O) and the mixture was stirred at
20 °C for 3 h, and then evaporated. The residue was dissolved in
CH2Cl2 (10 mL), washed with H2O (10 mL), dried (MgSO4), and
evaporated. The residue was purified by preparative TLC (10%
MeOH–CH2Cl2) to produce pure 7i (1.5 mg, 51%), whose 1H NMR
spectrum was identical to that reported previously.38
4,5,6-Tri-O-benzyl-D-myo-inositol (8i)
To a solution of 8a (8 mg, 13.2 mmol) in THF (0.5 mL) was added
1 M Bu4NF in THF (0.2 mL, containing 5% H2O) and the mixture
was stirred at 20 °C for 15 h, and then evaporated. The residue was
dissolved in CH2Cl2 (15 mL), washed with H2O (15 mL), dried
(MgSO4), and evaporated. The residue was purified by chromatog-
raphy (10% MeOH in CH2Cl2) to give pure 8i (4.9 mg, 83%) whose
1H NMR spectrum was identical to that reported previously.39
13C NMR (CDCl3): d = 138.45, 138.42, 138.3, 128.4, 128.1, 128.0,
127.81, 127.77, 127.73, 127.69, 127.4, 127.2, 127.1, 81.8, 81.0,
80.1, 75.2, 75.1, 73.5, 71.7, 70.9, 70.8, 17.9, 17.8, 12.2.
FAB-HRMS (NBA/NaI): m/z calcd for C36H50O6Si + Na (M + Na+):
629.3276; found: 629.3278.
(4S,5R,6S)-Tribenzyloxy-(3R)-triisopropylsilyloxyocta-1,7-di-
ene (12)
To the crude mixture of 3 and 4 (1:8.5, 0.72 g, 1.6 mmol) obtained
as described in the previous paper,35 in DMF (3.8 mL) and pyridine
(0.38 mL) was added AgNO3 (1.1 g, 6.5 mmol) followed by triiso-
propylsilyl chloride (0.7 mL, 3.3 mmol) at 20 °C. The mixture was
stirred for 2 h at 20 °C, after which it was diluted with Et2O (10 mL)
and H2O (10 mL). The aqueous layer was separated and extracted
with additional Et2O (3 × 10 mL). The combined organic extracts
were washed with brine, dried (MgSO4), and evaporated. The resi-
due was chromatographed (hexane–Et2O, 97:3) to give 5 (0.072 g,
7% over 3 steps) and 12 (0.62 g, 57% over 3 steps); [a]D25 +18.2 (c
0.2, CHCl3).
1H NMR (CDCl3): d = 7.35–7.24 (m, 15 H), 6.15–6.04 (m, 1H),
5.96–5.85 (m, 1 H), 5.29–5.15 (m, 4 H), 4.88 (d, J = 11.0 Hz, 1 H),
4.80–4.67 (m, 4 H), 4.62–4.56 (m, 2 H), 4.08 (dd, J = 6.1, 7.2 Hz, 1
H), 3.84 (dd, J = 2.5, 6.1 Hz, 1 H), 3.59 (yt, J = 5.6 Hz, 1 H), 1.50–
0.80 (m, 21 H).
Acknowledgment
A. K. would like to acknowledge the financial support from the U.S.
National Institutes of Health (RR-16480 and CA-99957) under the
BRIN/INBRE and AREA programs. M.D. acknowledges financial
support from the National Institutes of Health (DK-44589 and GM-
84819). The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National
Institutes of Health.
References
(1) Potter, B. V. L.; Lampe, D. Angew. Chem., Int. Ed. Engl.
1995, 34, 1933.
(2) Berridge, M. J.; Irvine, R. F. Nature 1989, 341, 197.
(3) Varela-Nieto, I.; Leon, Y.; Caro, H. N. Comp. Biochem.
Physiol., B: Comp. Biochem. 1996, 115, 223.
(4) Jones, D. R.; Varela-Nieto, I. Mol. Med. 1999, 5, 505.
(5) Stralfors, P. Bioessays 1997, 19, 327.
Synthesis 2008, No. 19, 3148–3154 © Thieme Stuttgart · New York