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Synlett 2012; 23(19): 2822-2826
DOI: 10.1055/s-0032-1317520
letter
© Georg Thieme Verlag Stuttgart · New York

A Concise Total Synthesis of (+)-Cladospolide D

Debjani Si
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India   Fax: +91(22)25723480   eMail: kpk@chem.iitb.ac.in
,
Krishna P. Kaliappan*
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India   Fax: +91(22)25723480   eMail: kpk@chem.iitb.ac.in
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Publikationsverlauf

Received: 05. September 2012

Accepted after revision: 08. Oktober 2012

Publikationsdatum:
09. November 2012 (online)

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Dedicated to Professor M. Periasamy (University of Hyderabad) on the occasion of his 60th birthday

Abstract

A short and convergent total synthesis of (+)-cladospolide D is delineated, which involves olefin cross metathesis and furan oxidation to access the γ-oxo-α,β-unsaturated acid and Yamaguchi lactonization to construct the 12-membered ring as key steps.

Key words

olefin cross-metathesis - Julia–Kocienski olefination - Yamaguchi lactonization - cladospolides - total synthesis

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References and Notes

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  • 22 Experimental Details and Spectral Data for Selected Compounds (5R,11S,Z)-5-(tert-Butyldimethylsilyloxy)-11-methylcyclododec-2-ene-1,4-dione (41) To a stirred solution of hydroxy acid 40a (60 mg, 0.20 mmol) and Et3N (55 μL, 0.40 mmol) in anhyd THF (5 mL) was added 2,4,6-trichloroenzoyl chloride (40 μL, 0.26 mmol) at 0 °C, and the resulting mixture was stirred for a further 2 h. The reaction mixture was then diluted with anhyd toluene (10 mL), was added to a refluxing solution of DMAP (51 mg, 0.40 mmol) in toluene (60 mL) at a rate of 3 mL/h and was refluxed for further 8 h. The resulting mixture was cooled to r.t., quenched with a sat. NaHCO3 solution (20 mL), and the aqueous layer was extracted with EtOAc (3 × 20 mL). The combined organic fractions were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (8% EtOAc in hexanes) to afford macrolactone 41 (17 mg, 25%) as an oily liquid. Rf = 0.30 (10% EtOAc in hexanes); [α]D 20 +72.5 (c 0.9, CHCl3). IR (neat): 2930, 2857, 2254, 1722, 1463, 1379, 1258, 1101, 1018 cm–1. 1H NMR (400 MHz, CDCl3): δ = 6.75 (d, J = 12.5 Hz, 1 H), 6.25 (d, J = 12.5 Hz, 1 H), 4.94–4.89 (m, 1 H), 4.33 (dd, J = 7.5, 3.8 Hz, 1 H), 1.97–1.89 (m, 1 H), 1.79–1.24 (m, 9 H), 1.28 (d, J = 6.1 Hz, 3 H), 0.94 (s, 9 H), 0.11 (s, 3 H), 0.10 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 203.4, 166.5, 133.7, 130.8, 76.4, 74.1, 33.5, 30.5, 26.4, 26.0, 25.9, 22.3, 21.3, 20.2, 18.3, 14.3, –4.5,–4.9. ESI-HRMS: m/z calcd for C18H33O4Si: 341.2148; found: 341.2152. (+)-Cladospolide D (5) 6b,c To a plastic flask was added lactone 41 (8 mg, 0.023 mmol) and 5% HF in MeCN (26 μL) at r.t. The reaction mixture was stirred for 8 h, and then EtOAc was added to dilute the reaction solution. The reaction mixture was washed with NaHCO3, extracted with EtOAc (3 × 5 mL), dried over anhyd. Na2SO4, filtered, and evaporated under reduced pressure to leave the crude product which was then purified using silica gel column chromatography (12% EtOAc in hexanes) to give cladospolide D (5.3 mg, 56%) as a colorless oil. Rf = 0.25 (10% EtOAc in hexanes); [α]D 20 +55.1 (c 0.1, MeOH). IR (neat): 3468, 2930, 2854, 1725, 1462, 1101, 1012 cm–1. 1H NMR (400 MHz, CDCl3): δ = 6.42 (d, J = 13.4 Hz, 1 H), 6.31 (d, J = 13.4 Hz, 1 H), 5.26–5.21 (m, 1 H), 4.68–4.65 (m, 1 H), 3.20 (d, J = 5.5 Hz, 1 H), 1.96–1.92 (m, 1 H), 1.71–1.64 (m, 3 H), 1.52–1.28 (m, 6 H), 1.30 (d, J = 6.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 203.6, 165.3, 133.4, 131.1, 73.6, 71.6, 33.3, 31.2, 23.1, 21.7, 21.6, 20.8. ESI-HRMS: m/z calcd for C12H18O4Na: 249.1103; found: 249.1104.