Synthesis 2005(19): 3225-3228  
DOI: 10.1055/s-2005-918449
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of the C1-C21 Southern Hemisphere of the Originally Proposed Structure of Spirastrellolide A

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

Publication History

Received 8 August 2005
Publication Date:
27 October 2005 (online)

Abstract

A stereocontrolled synthesis of the C1-C21 [6,6]-spiro­acetal-containing domain of the originally assigned structure of spirastrellolide­ A is reported, exploiting asymmetric boron aldol methodology and an alkyne addition to a C17 aldehyde. Comparison of the 1H NMR data obtained for this synthetic fragment with that for the corresponding region of spirastrellolide suggested some stereochemical reassignment was required.

    References

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5

In addition to the originally proposed structure by Professor Andersen, as reported in ref. 1, a preliminary stereochemical assignment was made by us for the C1-C11 region.

11

All new compounds gave spectroscopic data in agreement with the assigned structures. Compound 2 had [α]D 22 = +34.5 (c 0.80, CHCl3); 1H NMR (500 MHz, C6D6): δ = 7.78-7.83 (m, 4 H, ArH), 7.22-7.29 (m, 6 H, ArH), 5.60 (dd, J = 9.9, 2.4 Hz, 1 H, H15), 5.51 (dd, J = 9.9, 1.7 Hz, 1 H, H16), 4.38 (m, 1 H, H11), 4.22 (m, 1 H, H9), 4.07 (m, 1 H, H3), 4.03 (m, 1 H, H7), 3.94 (m, 1 H, H21eq.), 3.88 (m, 3 H, 2 × H1, H21ax.), 3.81 (m, 1 H, H13), 3.15 (m, 1 H, H20), 3.10 (s, 3 H, OMe), 2.12 (m, 1 H, H8), 2.10 (m, 1 H, H2), 2.09 (1H, m, H10), 2.04 (m, 1 H, H10), 2.02 (m, 1 H, H14), 1.97 (m, 1 H, H19ax.), 1.93 (m, 2 H, 2 × H12), 1.84 (m, 1 H, H18eq., H19eq.), 1.82 (m, 1 H, H2), 1.76 (m, 1 H, H8), 1.65 (m, 1 H, H6eq.), 1.58 (m, 1 H, H4eq.), 1.50 (m, 1 H, H18ax.), 1.49 (m, 2 H, 2 × H5), 1.36 (m, 1 H, H6ax.), 1.25 (m, 1 H, H4ax.), 1.19 (s, 9 H, Si t Bu), 1.05 (s, 9 H, Si t Bu), 1.03 (s, 9 H, Si t Bu), 0.80 (d, J = 7.1 Hz, 3 H, Me14), 0.26 (s, 3 H, SiMe), 0.28 (s, 3 H, SiMe), 0.24 (s, 3 H, SiMe), 0.20 (s, 3 H, SiMe); 13C NMR (125 MHz, C6D6): δ = 135.8, 135.7, 134.2, 134.1, 134.0, 129.7, 129.4, 93.0, 74.9, 71.0, 68.4, 68.3, 67.7, 67.6, 63.7, 61.5, 55.7, 46.6, 43.0, 42.5, 36.3, 34.5, 34.3, 30.8, 29.8, 27.0, 26.1, 26.0, 25.3, 19.3, 18.8, 18.2, 18.1, 17.0, -3.5, -3.7, -3.9, -4.0; HRMS (ES+): m/z [M + H]+ calcd for C51H87O7Si3: 895.5754; found: 895.5752.