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Synlett
Volumn , Issue 10, 2008, Pages 1523-1525
Efficient synthesis of (3R,5S)-3,5,6-trihydroxyhexanoic acid derivative as a chiral side chain of statins
Author keywords

3,5,6 trihydroxy heptanoic acid; Chiral side chain; Hydration; Selective protection; Statins
Indexed keywords

1 NAPHTHOYL CHLORIDE; 3,5,6 TRIHYDROXYHEXANOIC ACID DERIVATIVE; ACETIC ACID DERIVATIVE; DIOXANE; HEXANOIC ACID DERIVATIVE; HYDROXYL GROUP; LITHIUM CHLORIDE; PIVALOYL CHLORIDE; PYRIDINE; STATINE DERIVATIVE; TERT BUTYL [6 HYDROXYMETHYL 2,2 DIMETHYL 1,3 DIOXAN 4 YL]ACETATE;
EID: 46449135092     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/S-2008-1078428     Document Type: Article
Times cited : (13)
References (29)
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    • For a highlight on the chemoenzymatic synthesis of statin side chains, see
    • For a highlight on the chemoenzymatic synthesis of statin side chains, see: Müller, M. Angew. Chem. Int. Ed. 2005, 44, 362.
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    • Müller, M.1
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    • Preparation of 4a,b 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 x 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 x 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
    • 4 and concentrated. Column chromatography provided a mixture of 4a and 4b (1.28 g, 86% over two steps).
  • 24
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    • Immobilized lipase was used for regioselective acetylation of 4. See: Blacker, A. J, Reeve, C. D, Holt, R. A. US 7157255, 2007;
    • Immobilized lipase was used for regioselective acetylation of 4. See: Blacker, A. J.; Reeve, C. D.; Holt, R. A. US 7157255, 2007;
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    • 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 and diluted with EtOAc (20 mL, The organic phase was washed twice with 1 N H2SO4 (2 x 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 1H NMR (300 MHz, CDC13, 5, 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, δ, 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, CDC1
    • 3): δ = 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].
  • 28
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    • 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. NaHCO 3 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
    • D -3.7 (c 14.9 in MeOH); see: Wess G., Kesseler K., Baader E., Beck G.; US 4977279, 1990;
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    • Chem. Abstr. 1990, 112, 55602.
    • (1990) Chem. Abstr , vol.112 , pp. 55602

* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.