Non-iterative asymmetric synthesis of C-15 polyketide spiroketals

The 2,2'-methylenebis[furan] (1) was converted to 1-{(4R,6S))-6-[(2R)-2,4-dihydroxybutyl]-2,2-dimethyl-1,3-dioxan-4-yl}-3- [(2R,4R)-tetrahydro-4,6-dihydroxy-2H-pyran-2-yl)propan-2-one ((+)-18) and its (4S)-epimer (-)-19 with high stereo- and enantioselectivity (Schemes 1-3). Under acidic methanolysis, (+)-18 yielded a single spiroketal, (3R)-4-1(1R,3S,4'R,5R,6'S,7R)-3',4',5',6'-tetrahydro-4'-hydroxy-7-methox yspiro[2,6-dioxabicyclo[3.3.1]nonane-3,2'-[2H]pyran]-6'-yl]butane-1,3-di ol ((-)-20), in which both O-atoms at the spiro center reside in equatorial positions, this being due to the tricyclic nature of (-)-20 (methyl pyranoside formation). Compound (-)-19 was converted similarly into the (4'S)-epimeric tricyclic spiroketal (-)-21 that also adopts a similar (3S)-configuration and conformation. Spiroketals (-)-20, (-)-21 and analog (-)-23, i.e., (1R,3S,4'R,5R,6'R)-3',4',5',6'-tetrahydro-6'-[(2S)-2-hydroxybut-3-enyl]- 7-methoxyspiro[2,6-dioxabicyclo[3.3.1]nonane-3,2'-[2H]pyran]-4'-ol, derived from (-)-20, were assayed for their cytotoxicity toward marine P388 lymphocytic leukemia and six human cancer cell lines. Only racemic ()-21 showed evidence of cancer-cell-growth inhibition (P388, ED50: 6.9 mug/ml).


Published in:
Helvetica Chimica Acta, 87, 6, 1493-1507
Year:
2004
ISSN:
0018-019X
Keywords:
Note:
Ecole Polytech Fed Lausanne, BCH, Lab Glycochim & Synth Asymetr, CH-1015 Lausanne, Switzerland. Arizona State Univ, Inst Canc Res, Tempe, AZ 85287 USA.
Laboratories:




 Record created 2005-11-09, last modified 2018-03-17


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