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Synlett 2010(4): 571-574  
DOI: 10.1055/s-0029-1219347
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthetic Studies towards Iriomoteolide 1a: Stereocontrolled Construction of C1-C9 and C11-C23 Segments Using Lactate Aldol Chemistry

Ian Paterson*, Philipp Rubenbauer
University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK
Fax: +44(1223)336362; e-Mail: ip100@cam.ac.uk;
Further Information

Publication History

Received 1 December 2009
Publication Date:
25 January 2010 (online)

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Abstract

The stereocontrolled construction of C1-C9 and C13-C23 segments of the cytotoxic macrolide iriomoteolide 1a is reported, exploiting boron aldol additions of enantiomeric lactate-derived ketones and a Suzuki-Miyaura cross-coupling reaction.

Key words

macrolide - anticancer - aldol reactions - cross-coupling - asymmetric synthesis

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14

Aldehyde 2: [α]D ²0 +32.0 (c 0.20, CHCl3). IR (neat): 2952, 2881, 1737, 1461, 1376, 1252, 1095, 1011 cm-¹. ¹H NMR (500 MHz, CDCl3): δ = 9.33 (1 H, s), 5.72-5.78 (1 H, m), 5.32 (1 H, d, J = 15.4 Hz), 3.65-3.70 (2 H, m), 2.13-2.18 (1 H, m), 1.81-1.87 (1 H, m), 1.57-1.64 (2 H, m), 1.42-1.48 (2 H, m), 1.38 (3 H, s), 1.06 (3 H, d, J = 6.2 Hz), 0.96 (9 H, t, J = 7.8 Hz), 0.95 (9 H, t, J = 7.8 Hz), 0.88 (9 H, s), 0.86 (3 H, d, J = 7.1 Hz), 0.85 (3 H, d, J = 6.9 Hz), 0.62 (6 H, q, J = 7.8 Hz), 0.58 (6 H, q, J = 7.8 Hz), 0.04 (3 H, s), 0.02 (3 H, s). ¹³C NMR (125 MHz, CDCl3): δ = 200.7, 133.2, 130.8, 80.2, 74.6, 71.4, 37.6, 37.3, 36.3, 33.9, 25.9, 22.7. HRMS (ES+): m/z calcd for C32H69O4Si3 [M + H+] 601.4504; found: 601.4509.

16

Dihydropyrone 3: [α]D ²0 -30.0 (c 0.10, CHCl3). IR (neat): 2931, 2856, 1709, 1512, 1249, 1095, 1034 cm-¹. ¹H NMR (500 MHz, CDCl3): δ = 7.24 (2 H, d, J = 8.6 Hz), 6.87 (2 H, d, J = 8.6 Hz), 5.79 (1 H, dt, J = 15.5, 6.8 Hz), 5.77 (1 H, s), 5.59 (1 H, ddt, J = 15.5, 7.2 Hz, 1.3 Hz), 4.52 (1 H, app t, J = 6.6 Hz), 4.41 (2 H, s), 3.80 (3 H, s), 3.42-3.47 (2 H, m), 2.36 (2 H, app qd, J = 6.7, 1.3 Hz), 2.26-2.33 (1 H, m), 1.94 (3 H, s), 1.15 (3 H, d, J = 7.2 Hz). ¹³C NMR (125 MHz, CDCl3): δ = 163.8, 160.4, 159.2, 132.8, 130.3, 129.2, 128.5, 116.3, 113.8, 83.2, 72.6, 68.9, 55.2, 37.6, 32.7, 21.4, 15.5. HRMS (ES+): m/z calcd for C19H24O4Na [M + Na+]: 339.1572; found: 339.1588.