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Synlett 2002(8): 1261-1264
DOI: 10.1055/s-2002-32968
LETTER
© Georg Thieme Verlag Stuttgart · New York

Enantioselective Taxanes Approach Using Both Enantiomers of the Same Building-Block. Part 1: Taxol® A-Ring Subunit

Gérard Audran, Jean-Pierre Uttaro, Honoré Monti*
Laboratoire de Réactivité Organique Sélective UMR 6516 Faculté des Sciences de St-Jérôme (case 551), Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
Fax: +33(4)91288862; e-Mail: honore.monti@univ.u-3mrs.fr;
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Publication History

Received 14 May 2002
Publication Date:
25 July 2002 (online)

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Abstract

An efficient enantioselective synthesis of fully-oxygenated Taxol® A-ring subunit has been achieved using (-)-karahana lactone, (-)-2, as an enantiopure starting building-block and a diastereoselective allylic hydroxylation as the key step.

Key words

stereoselectivity - enantioselective synthesis - Taxol® - antitumor agents

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Preparation of (-)-3. To a stirred solution of karahana lactone (-)-2 [6] (400 mg, 2.41 mmol) in dry CH2Cl2 (40 mL) was added selenium dioxide (107 mg, 0.96 mmol), tert-butyl hydroperoxide (70 wt% in water, 868 mg, 9.64 mmol) and a catalytic amount of salicylic acid under an argon atmosphere. The reaction mixture was heated to reflux for 3 d, cooled to r.t. and Na2SO3 (2.5 g, 20 mmol) and 1 mL of water were added. The mixture was stirred for a further 30 min, filtered through a pad of MgSO4 and concentrated. After purification by crystallization from Et2O-hexane, 354 mg of pure alcohol (-)-3 were obtained as white crystals (rdt 85%).

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Spectroscopic data of compounds (-)-3 and (-)-1: (-)-3: mp 155 °C, [α]D 25 -142.9 (c 1.0, CHCl3). IR (KBr): 3440, 3091, 1759, 1036, 905 cm-1. 1H NMR (500 MHz, CDCl3): δ = 5.18 (s, 1 H, H-9), 5.08 (s, 1 H, H-9), 4.42 (d, J = 6.1 Hz, 1 H, H-3), 4.36 (br. d, J = 3.7 Hz, 1 H, H-5), 2.77 (s, 1 H, H-1), 2.22 (dd, J = 15.7, 3.8 Hz, 1 H, Hα-4), 2.08 (ddd, J = 15.7, 6.1, 1.5 Hz, 1 H, Hβ-4), 1.21 (s, 3 H, CH3 β), 0.95 (s, 3 H, CH3 α).
13C NMR (125 MHz, CDCl3): δ = 176.6 (C-7), 143.9 (C-2), 117.0 (CH2-9), 84.3 (CH-5), 68.0 (CH-3), 56.6 (CH-1), 42.8 (C-8), 32.6 (CH2-4), 25.3 (CH3 ), 20.1 (CH3 ). Anal. Calcd for C10H14O3: C, 65.92; H, 7.74. Found: C, 65.64; H 7.72.
(-)-1: Mp 59 °C, [α]D 25 -39.0 (c 1.0, CHCl3). IR (KBr): 1661, 1630, 1254, 1104 cm-1. 1H NMR (200 MHz, CDCl3): δ = 5.37 (s, 1 H, H-7), 4.26 (t, J = 4.8 Hz, 1 H, H-5), 4.12-4.05 (m, 2 H, Hdioxolane), 3.94-3.87 (m, 2 H, Hdioxolane), 2.76 and 2.60 (ABX, J = 13.7, 5.8, 4.4 Hz, 2 H, H-6), 1.92 (s,
3 H, H-8), 1.30 (s, 3 H, CH3) 1.22 (s, 3 H, CH3), 0.85 (s, 9 H, (CH3)3C-), 0.06 (s, 3 H, CH3-Si), 0.05 (s, 3 H, CH3-Si).
13C NMR (50 MHz, CDCl3): δ = 212.2 (C-1), 139.1 (C=), 133.0 (C=), 102.0 (CH-7), 72.2 (CH-5), 64.7 (CH2dioxolane), 64.4 (CH2dioxolane), 47.1 (C-2), 45.6 (CH2-6), 25.6 (CH3)3C-), 24.6 (CH3), 23.8 (CH3), 17.9 (CH3)3C-), 17.2 (CH3-8), -4.6 (CH3-Si), -4.8 (CH3-Si). Anal. Calcd for C18H32O4Si: C, 63.49; H, 9.47. Found: C, 63.67; H 9.45.