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Synlett 2007(18): 2891-2893  
DOI: 10.1055/s-2007-990958
LETTER
© Georg Thieme Verlag Stuttgart · New York

Concise Total Synthesis of (-)-Muricatacin and (-)-iso-Cladospolide B Using Chemoselective Cross-Metathesis

Laurent Ferrié, Sébastien Reymond, Patrice Capdevielle, Janine Cossy*
Laboratoire de Chimie Organique, ESPCI, CNRS, 10 Rue Vauquelin, 75231 Paris Cedex 05, France
Fax: +33(1)40794660; e-Mail: janine.cossy@espci.fr;
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Publication History

Received 6 July 2007
Publication Date:
19 October 2007 (online)

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Abstract

A concise total synthesis of (-)-muricatacin and (-)-iso-cladospolide B has been achieved by using chemoselective cross-metatheses and asymmetric dihydroxylations. These key reactions allow a fast access to α-hydroxybutyrolactones.

Key words

cross-coupling - metathesis - chemoselectivity - dihydroxylations - total synthesis

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Compound 5 (prepared in >10 mmol scale): IR (neat): 3000-2800, 2200, 1650, 1593, 1427, 1339, 1167,1095, 995, 953, 832, 789 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.39 (dd, J = 15.0, 11.3 Hz, 1 H), 6.47 (t, J = 11.3 Hz, 1 H), 6.05 (d, J = 11.3 Hz, 1 H), 6.01 (dq, J = 15.1, 6.9 Hz, 1 H), 3.66 (s, 3 H), 3.20 (s, 3 H), 1.84 (d, J = 6.9 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 167.4 (br s), 143.1 (d), 139.0 (d), 128.6 (d), 113.5 (d), 61.5 (q), 32.1 (br q), 18.5 (q). MS (EI): m/z (%) = 155 (21) [M+•], 124 (2) [M - OMe+], 95 (100) [M - NMeOMe+], 67 (60) [95 - CO+].

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Modified AD-mix: OsO4 (2 mol%), (DHQ)2PHAL for AD-mix α (4 mol%), or (DHQD)2PHAL for AD-mix β (4 mol%), MeSO2NH2 (1 equiv), K3Fe(CN)6 (3 equiv), K2CO3 (3 equiv), t-BuOH-H2O, see ref. 8c.

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The ee of lactone 7 was determined by chiral supercritic fluid chromatography (SFC) [Chiralcel OD-H, CO2 100 bar, 5 mL/min, 7% i-PrOH, λ = 220 nm, t R (S,S) = 5.87 min, t R (R,R) = 6.50 min].

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(-)-Muricatacin (prepared in <1 mmol scale): mp 69-72 °C (synthetic product3j mp 68-70 °C); [α]D 20 -19.6 (c 1.0, CHCl3) {isolated natural product5 [α]D 20 -16.1; reported synthetic product3j [α]D 23 -19.5 (c 2.1, CHCl3)}; IR (neat): 3396, 3000-2800, 1727, 1470, 1176 cm-1. 1H NMR (400 MHz, CDCl3): δ = 4.41 (td, J = 7.5, 4.6 Hz, 1 H), 3.57 (m, 1 H), 2.62 (ddd, J = 17.8, 9.9, 5.0 Hz, 1 H), 2.54 (ddd, J = 17.8, 9.5, 9.0 Hz, 1 H), 2.30-2.20 (m, 1 H), 2.17-2.06 (m, 1 H), 1.88 (m, 1 H, OH), 1.60-1.18 (m, 22 H), 0.88 (t, J = 6.7 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 177.1 (s), 82.9 (d), 73.7 (d), 33.0 (t), 31.9 (t), 29.6 (t), 29.6 (t), 29.6 (t), 29.5 (t), 29.5 (t), 29.5 (t), 29.3 (t), 28.9 (t), 25.4 (t), 24.1 (t), 22.7 (t), 14.1 (q). MS (EI): m/z (%) = 283 (1) [M - H+], 207 (9), 97 (14), 86 (100), 69 (17), 55 (17). ESI-HRMS: m/z calcd for C17H32O3 + Na+: 307.2244; found: 307.2239.

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(-)-iso-Cladospolide B (prepared in <1 mmol scale): [α]D 20 -61.6 (c 0.50, MeOH); {isolated natural product4c [α]D 28 -61.0 (c 16.6, MeOH)}. IR (neat): 3487, 3000-2800, 1745, 1462, 1329, 1165, 1097, 1042, 828 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.46 (dd, J = 5.8, 1.5 Hz, 1 H), 6.18 (dd, J = 5.8, 2.0 Hz, 1 H), 4.99 (dtapp, J = 4.5, 1.8 Hz, 1 H), 3.86-3.66 (m, 2 H), 2.21-1.81 (m, 2 H, OH), 1.66-1.26 (m, 10 H), 1.18 (d, J = 6.2 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 172.9 (s), 153.8 (d), 122.7 (d), 86.2 (d), 71.7 (d), 68.0 (d), 39.0 (t), 33.0 (t), 29.3 (t), 25.5 (t), 25.4 (t), 23.5 (q). ESI-HRMS (ESI): m/z calcd for C12H20O4 + Na+: 251.1248; found: 251.1253.