Preparation of an A-ring building block for the total synthesis of 1α,25-dihydroxy vitamin D3 and structurally related congeners: Lipase-catalyzed stereoselective esterification of a suitable epoxyalcohol

Tetrahedron Asymmetry

Volumn 11, Issue 13, 2000, Pages 2665-2668

  Ferraboschi, Patrizia ^a   Reza Elahi, Shahrzad ^a   Scotti, Luca ^a   Santaniello, Enzo ^a  

^a UNIVERSITY OF MILAN   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ALCOHOL; CALCITRIOL; CALCITRIOL DERIVATIVE; EPOXYALCOHOL; ERGOCALCIFEROL; ORGANIC SOLVENT; TRIACYLGLYCEROL LIPASE; UNCLASSIFIED DRUG;

ACYLATION; ARTICLE; CATALYSIS; CONTROLLED STUDY; DRUG SYNTHESIS; ESTERIFICATION; PRIORITY JOURNAL; STEREOCHEMISTRY; TECHNIQUE;

EID: 0034647611     PISSN: 09574166     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0957-4166(00)00239-1     Document Type: Article

References (16)

1. Hamada, K.; Shinomiya, H. Drugs of the Future 1993, 18, 1057.
2. Zeelen, F. J. Adv. Drug Res. 1992, 22, 149.
3. Zhu, G.-D.; Okamura, W. H. Chem. Rev. 1995, 95, 1877.
4. Toh, H. T.; Okamura, W. H. J. Org. Chem. 1983, 48, 1414.
5. 2 3.
6. 2-7), 4.60 (s, 1H, CH-19), 4.92 (s, 1H, CH-19), 5.41 (t, 1H, CH-6).
7. 3 congeners. Among many available examples, see: (a) Sardina, F. J.; Mouriño, A.; Castedo, L. J. Org. Chem. 1986, 51, 1264. (b) Hatakeyama, S.; Ikeda, T.; Irie, H.; Izumi, C.; Mori, H.; Uenoyama, K.; Yamada, H.; Nishizawa, M. J. Chem. Soc., Chem. Commun. 1995, 1959.
8. 3 congeners. Among many available examples, see: (a) Sardina, F. J.; Mouriño, A.; Castedo, L. J. Org. Chem. 1986, 51, 1264. (b) Hatakeyama, S.; Ikeda, T.; Irie, H.; Izumi, C.; Mori, H.; Uenoyama, K.; Yamada, H.; Nishizawa, M. J. Chem. Soc., Chem. Commun. 1995, 1959.
9. Kiegel, J.; Wovkulich, P. M.; Uskokovic, M. R. Tetrahedron Lett. 1991, 32, 6057.
10. 2/t-BuOOH epoxidation showed the most significant resonances at 3.10 (t, 0.24H, CH, 6α-isomer) and 3.16 (dd, 0.76H, CH 6β-isomer) ppm corresponding to a 3:1 ratio of β:α-epimers.
11. Purification of the epoxyalcohol mixture was carried out by column chromatography (neutral aluminum oxide III: crude mixture, 10:1). Elution with hexane:ethyl acetate (8:2) afforded pure β-epoxyalcohol 7 (30% yields).
12. For a recent review on the preparation of chiral synthons by enzymatic acylation and esterification reactions, see: Santaniello, E.; Reza-Elahi, S.; Ferraboschi, P. In Stereoselective Biocatalysis; Patel, R. N., Ed.; M. Dekker: New York, 2000; pp. 415-460.
13. 3 is not selective, since the β/α-acetate mixture 9 is in the same ratio as the starting material.
14. Candida antarctica lipase (CAL B, Novozym 435) was a gift from Novo Nordisk (Italy).
15. 2O) from the α/β-epoxide 6:7 (1:3 ratio): 3.08 (t, 0.25H, CH, 6α-isomer) and 3.16 (dd, 0.75H, CH, 6β-isomer) ppm.
16. For an extensive review on the application of biocatalysis to steroids and, in particular, to the preparation of vitamin D synthons, see: Ferrero, M.; Gotor, V. In Stereoselective Biocatalysis; Patel, R. N., Ed.; M. Dekker: New York, 2000; pp. 579-631.