Synlett 2014; 25(20): 2887-2890
DOI: 10.1055/s-0034-1379476
letter
© Georg Thieme Verlag Stuttgart · New York

An Expeditious Asymmetric Synthesis of the Polyketide Unit Present in HIV-Inhibitory Depsipeptides Aetheramide A and B

Omkar Revu
Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560 012, India   Fax: +91(80)23600529   Email: prasad@orgchem.iisc.ernet.in
,
Kavirayani R. Prasad*
Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560 012, India   Fax: +91(80)23600529   Email: prasad@orgchem.iisc.ernet.in
› Author Affiliations
Further Information

Publication History

Received: 05 August 2014

Accepted after revision: 21 September 2014

Publication Date:
27 October 2014 (online)


Abstract

The enantioselective synthesis of the polyketide unit present in depsipeptides aetheramide A and B, which possess potent HIV-inhibitory activity, is accomplished from a chiral furyl carbinol.

Supporting Information

 
  • References and Notes

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  • 4 Numbering of the macrolactone as reported by Muller et al. in the isolation paper, see ref. 3.
  • 5 While this manuscript was in preparation, a report concerning the synthesis of the macrocyclic aetheramide A was published, see: Ghosh AK, Rao KV, Akasapu S. Tetrahedron Lett. 2014; 55: 5191
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  • 9 The diastereomeric ratio of the product was found to be ca. 95:5, as estimated by 1H NMR spectroscopic analysis. The stereochemistry of the major diastereomer was assigned based on previously reported reduction of structurally similar ketones. See refs. 7a–d.
  • 10 The Grignard reagent was prepared from the corresponding tetrahydro-2H-pyran-2-yloxybutyl bromide, which was synthesized according to a previously described procedure, see: Grieco PA, Larsen SD. J. Org. Chem. 1986; 51: 3553
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  • 13 All compounds exhibited satisfactory analytical data. Data for selected compounds: Compound 8: [α]D 24 +71.5 (c 1.05, CHCl3); IR (neat): 3442, 2954, 2929, 1700, 1587 cm–1; 1H NMR (400 MHz, CDCl3): δ = 7.40–7.22 (m, 5 H), 7.08 (d, J = 11.2 Hz, 1 H), 6.58–6.45 (m, 1 H), 5.81 (dd, J = 15.2, 4.8 Hz, 1 H), 4.44 (d, J = 7.2 Hz, 1 H), 4.27 (br. s, 1 H), 4.20 (q, J = 7.2 Hz, 2 H), 2.97 (d, J = 2.4 Hz, 1 H), 1.89 (s, 3 H), 1.28 (t, J = 7.2 Hz, 3 H), 0.90 (s, 9 H), 0.05 (s, 3 H), –0.18 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 168.5, 140.5, 138.8, 137.3, 128.1 (2 × C), 127.8, 127.5, 127.1, 127.0 (2 × C), 78.1, 76.6, 60.6, 25.7 (3 × C), 18.1, 14.3, 12.6, –4.6, –5.0; HRMS: m/z calcd for C22H34O4Si + Na: 413.2124; found: 413.2124. Compound 14: [α]D 24 –48.8 (c 0.65, CHCl3); IR (neat): 3450, 2932, 2888, 1725, 1458, 1099 cm–1; 1H NMR (400 MHz, CDCl3): δ = 7.35–7.20 (m, 5 H), 6.36 (dd, J = 15.0, 11.2 Hz, 1 H), 5.89 (d, J = 11.2 Hz, 1 H), 5.43 (dd, J = 15.2, 7.2 Hz, 1 H), 4.68 (d, J = 5.2 Hz, 1 H), 4.63 (dd, J = 6.8, 2.0 Hz, 1 H), 4.55 (dd, J = 6.8, 2.0 Hz, 1 H), 4.19 (t, J = 6.8 Hz, 1 H), 3.62–3.52 (m, 2 H), 3.40 (t, J = 7.2 Hz, 1 H), 3.10 (br s, 6 H), 2.31 (br s, 1 H), 1.56 (s, 3 H), 1.55–1.45 (m, 2 H), 1.44–1.20 (m, 4 H), 0.84 (s, 9 H), 0.02 (s, 3 H), –0.12 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 141.4, 137.2, 129.9, 128.7, 127.5 (2 × C), 127.1, 127.0 (2 × C), 126.9, 94.3, 87.0, 80.7, 77.7, 62.3, 55.7, 55.1, 33.2, 32.4, 25.7 (3 × C), 21.9, 18.1, 10.9, –4.9, –5.1; HRMS: m/z calcd for C27H46O5Si + Na: 501.3012; found: 501.3013. Compound 3: [α]D 24 –19.4 (c 0.5, CHCl3); IR (neat): 3400, 2919, 1710, 1655, 1087 cm–1; 1H NMR (400 MHz, CDCl3): δ = 7.40–7.15 (m, 5 H), 6.34 (dd, J = 15.2, 11.0 Hz, 1 H), 5.87 (d, J = 10.8 Hz, 1 H), 5.45–5.30 (m, 2 H), 4.70 (d, J = 5.2 Hz, 1 H), 4.66 (d, J = 6.8 Hz, 1 H), 4.58 (d, J = 6.8 Hz, 1 H), 4.21 (t, J = 6.2 Hz, 1 H), 4.10 (d, J = 7.8 Hz, 1 H), 3.42 (dd, J = 7.2, 4.0 Hz, 1 H), 3.15 (s, 3 H), 3.14 (s, 3 H), 2.70–2.58 (m, 1 H), 2.28–1.95 (m, 2 H), 1.90–1.80 (m, 1 H), 1.61 (s, 3 H), 1.60 (s, 3 H), 1.45–1.20 (m, 3 H), 1.14 (d, J = 6.8 Hz, 3 H), 0.91 (d, J = 8.0 Hz, 9 H), 0.87 (s, 9 H), 0.58 (q, J = 8.0, 6 H), 0.04 (s, 3 H), –0.10 (s, 3 H); 13C NMR (100 MHz, CDCl3): δ = 177.8, 141.6, 137.4, 137.3, 135.6, 130.1, 128.8, 127.6 (2 × C), 127.2 (3 × C), 127.1, 94.5, 87.6, 80.9, 80.4, 77.8, 55.7, 55.2, 33.8, 29.7, 26.8, 25.8 (3 × C), 25.7, 18.3, 12.9, 11.0, 10.9, 6.8 (3 × C), 4.7 (3 × C), –4.8, –4.9; HRMS: m/z calcd for C39H68O7Si2 + Na: 727.4401; found: 727.4401.