LETTER
Synthesis of (3R,5S)-3,5,6-Trihydroxyhexanoic Acid Derivative
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and diluted with EtOAc (20 mL). The organic phase was
washed twice with 1 N H2SO4 (2 × 30 mL). The separated
organic layer was dried over MgSO4, and concentrated.
Column chromatography (EtOAc–hexane = 1:20 to 1:3) of
the residue provided 7a and 7d in 85% yield, respectively.
Spectroscopic Data of 7a
References and Notes
(1) Istvan, E. S.; Deisenhofer, J. Nature (London) 2001, 292,
1160.
(2) Joshi, N.; Bhirud, S. B.; Chandrasekhar, B.; Rao, K. E.;
Damle, S. US 7312329, 2005; Chem. Abstr. 2005, 143,
26633.
(3) Satyanarayana Reddy, M.; Thirumalai Rajan, S.; Sahadeva
Reddy, M. WO 2007125547, 2007; Chem. Abstr. 2007, 147,
522015.
(4) Hiyama, T.; Minami, T.; Takahashi, K. Bull. Chem. Soc.
Jpn. 1995, 68, 364.
(5) For a highlight on the chemoenzymatic synthesis of statin
side chains, see: Müller, M. Angew. Chem. Int. Ed. 2005, 44,
362.
(6) Wess, G. Tetrahedron Lett. 1990, 31, 2545.
(7) Nishiyama, A.; Horikawa, M.; Yasohara, Y.; Ueyama, N.;
Inoue, K. US 7094594, 2006; Chem. Abstr. 2001, 136,
904153.
(8) Evans, D. A.; Carreira, E. M. J. Org. Chem. 1991, 56, 741.
(9) Evans, D. A.; Kozlowski, M. C.; Murry, J. A.; Burgey, C. S.;
Campos, K. R.; Connel, B. T.; Staples, R. J. J. Am. Chem.
Soc. 1999, 121, 669.
(10) Beck, G.; Kessler, K.; Jendralla, H. Synthesis 1995, 1014.
(11) (a) Hunter, T. J.; O’Doherty, G. A. Org. Lett. 2001, 3, 1049.
(b) Miyazawa, M.; Matsuoka, E.; Sasaki, S.; Oonuma, S.;
Maruyama, K.; Miyashita, M. Chem. Lett. 1998, 109.
(12) Solladié, G.; Bauder, C.; Rossi, L. J. Org. Chem. 1995, 60,
7774.
(13) (a) Wolberg, M.; Hummel, W.; Wandrey, C.; Müller, M.
Angew. Chem. Int. Ed. 2000, 39, 4306. (b) Wolberg, M.;
Hummel, W.; Wandrey, C.; Müller, M. Chem. Eur. J. 2001,
7, 4562.
(14) (a) Kapa, P. K.; Oljan, R. Tetrahedron Lett. 1984, 25, 2435.
(b) Honda, T.; Endo, K.; Ono, S. Chem. Pharm. Bull. 2000,
48, 1545.
(15) Shin, H.; Choi, B. S.; Lee, K. K.; Choi, H.-w.; Chang, J. H.;
Lee, K. W.; Nam, D. H.; Kim, N.-S. Synthesis 2004, 2629.
(16) Scheffler, J.-L.; Bette, V.; Mortreux, A.; Nowogrocki, G.;
Carpentier, J.-F. Tetrahedron Lett. 2002, 43, 2679.
(17) Preparation of 4a,b
1H NMR (300 MHz, CDCl3): d = 4.34 (m, 1 H), 4.09–4.24
(m, 2 H), 3.42 (s, 2 H), 2.96 (d, 1 H), 2.76 (d, J = 5.55 Hz, 2
H), 1.48 (s, 9 H), 1.23 (s, 9 H). 13C NMR (75 MHz, CDCl3):
d = 196.9, 172.9, 160.9, 76.4, 61.8, 60.2, 45.6, 40.7, 33.3,
22.5, 21.7. ESI-MS: m/z = 320 [M + NH4].
Spectroscopic Data of 7d
1H NMR (300 MHz, CDCl3): d = 7.33–8.90 (m, 7 H), 4.49
(m, 1 H), 4.35–4.39 (m, 2 H), 3.36 (s, 2 H), 2.71–2.87 (m, 2
H), 1.38 (s, 9 H). 13C NMR (75 MHz, CDCl3): d = 197.4,
162.0, 161.1, 128.5, 128.3, 126.1, 125.2, 123.3, 122.6,
121.4, 121.0, 120.5, 119.2, 76.9, 62.6, 60.6, 45.8, 40.9, 22.6.
ESI-MS: m/z = 395 [M + Na].
(20) Chen, K.-M.; Hardmann, G. E.; Prasad, K.; Repic, O.;
Shapiro, M. J. Tetrahedron Lett. 1987, 28, 155.
(21) (3R,5S)-{2,2-Dimethyl-6-trimethylacetoxymethyl-
[1,3]dioxan-4-yl}-acetic Acid tert-Butyl Ester (1)
Compound 7a (2.7 g, 9 mmol) was dissolved in a 5:1 mixture
of THF and MeOH (18 mL), cooled to –78 °C and treated
with Et2BOMe (10 mL, 10 mmol, 1 M in THF). After
stirring for 30 min, the resulting solution was treated with
NaBH4 (380 mg, 10 mmol) and stirred at –78 °C for 5 h. The
reaction was quenched with AcOH (5 mL) and solvent was
evaporated in vacuo. The residue was dissolved in
methanolic AcOH soln (50 mL, 3% v/v) and evaporated
again. The resulting mixture was dissolved in EtOAc (20
mL), and washd twice with a sat. NaHCO3 solution. The
organic phases were dried over anhyd MgSO4 and
concentrated. Column chromatography (EtOAc–
hexane = 1:10 to 1:2) of the residue gave diol compound
(2.3 g, 85%), 1.3 g (4.3 mmol) of which was dissolved in
acetone (5 mL) and treated with 2,2-dimethoxypropane (667
mg, 6.4 mmol) and PTSA (4 mg, 0.02 mmol). After stirring
at ambient temperature for 2 h, the reaction mixture was
quenched with Et3N. The reaction mixture was evaporated in
vacuo, and diluted with hexane (10 mL). The organic phase
was washed with a sat. NaHCO3 solution (2 × 10 mL). The
organic phases were dried over anhyd MgSO4 and
concentrated. Column chromatography (EtOAc–
hexane = 1:20 to 1:3) of the residue gave 8 (1.34 g, 91%).
Compound 8 (1.20 g, 3.5 mmol) was dissolved in EtOH (5
mL) and treated with NaOEt (1.6 g, 5.2 mmol). After stirring
at ambient temperature for 15 h, the reaction mixture was
quenched with solid NH4Cl. The reaction mixture was
evaporated in vacuo, and diluted with EtOAc (10 mL). The
separated organic layer was washed with H2O (10 mL) and
brine (10 mL), dried over anhyd MgSO4. After evaporation
of solvent, the crude product was purified by column
chromatography (EtOAc–hexane = 1:10 to 1:3) to give 1
(0.73 g, 81%). 1H NMR (300 MHz, CDCl3):d = 4.29 (m, 1
H), 4.01 (m, 1 H), 3.45–3.65 (m, 2 H), 2.65 (br s, 1 H), 2.38
(dd, J1 = 22.9 Hz, J2 = 7.1 Hz), 1.49 (s, 3 H), 1.45 (s, 9 H),
1.38 (s, 3 H), 1.26–1.61 (m, 2 H). 13C NMR (75 MHz,
CDCl3): d = 164.8, 93.5, 75.2, 64.4, 60.4, 37.3, 26.7, 24.6,
22.7, 14.4. MS: m/z = 261 [M + H]+. [a]D –3.7 (c 2.0 in
MeOH); lit.: [a]D –3.7 (c 14.9 in MeOH); see: Wess G.,
Kesseler K., Baader E., Beck G.; US 4977279, 1990; Chem.
Abstr. 1990, 112, 55602.
A solution of 2 (1.6 g, 6.8 mmol) in THF (30 mL) was treated
with DBU (1.3 mL, 8.6 mmol) at ambient temperature. After
20 h, the reaction mixture was quenched with 0.5 N HCl (30
mL). The organic phase was separated and the aqueous
phase was re-extracted with EtOAc (2 × 20 mL). The
combined organic layer was washed with aq NaHCO3
solution, dried with MgSO4, and concentrated in vacuo. The
crude 3 was dissolved in 9:1 mixture of H2O and THF (40
mL), and treated with LiCl (1.8 g, 42.6 mmol) and PTSA (81
mg, 0.42 mmol). The mixture was stirred for 20 h at ambient
temperature and quenched by solid NaHCO3 (71 mg, 0.85
mmol). The organic phase was separated and the aqueous
phase was re-extracted with EtOAc (5 × 10 mL). The
combined organic layer was dried with MgSO4 and
concentrated. Column chromatography provided a mixture
of 4a and 4b (1.28 g, 86% over two steps).
(18) Immobilized lipase was used for regioselective acetylation
of 4. See: Blacker, A. J.; Reeve, C. D.; Holt, R. A. US
7157255, 2007; Chem. Abstr. 2001, 136, 356851.
(19) Preparation of 7a and 7d
A cooled (ca. 0 °C) solution of 4a,b (10 mmol) in pyridine
(5 mL) was treated with protecting agent (10–11 mmol). The
resulting solution was stirred at the same temperature for 1 h
Synlett 2008, No. 10, 1523–1525 © Thieme Stuttgart · New York