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The first total synthesis of the marine fatty acid (±)-2-methoxy-13-methyltetradecanoic acid: a cytotoxic fatty acid to leukemia cells

2003; Elsevier BV; Volume: 126; Issue: 2 Linguagem: Inglês

10.1016/s0009-3084(03)00110-5

1873-2941

Néstor M. Carballeira, Heidyleen Cruz, Elsie A. Orellano, Fernando A. González,

Carbohydrate Chemistry and Synthesis

The recently discovered marine fatty acid (±)-2-methoxy-13-methyltetradecanoic acid was synthesized for the first time in six steps (26% overall yield) starting from commercially available methyl 12-methyltridecanoate. The synthetic approach provided enough material to corroborate the structure of the acid, which was recently identified in the sponge Amphimedon complanata from Aguadilla, Puerto Rico, and to test its cytotoxicity to three leukemia cell lines. The key step in the synthesis was the addition of trimethylsilyl cyanide to 12-methyltridecanal under triethylamine catalysis. Nuclear magnetic resonance data are provided for the first time for this methoxylated fatty acid and the synthetic approach utilized is of general applicability since it can be used in the synthesis of other methyl-branched 2-methoxylated fatty acids. We also report that the acid (±)-2-methoxy-13-methyltetradecanoic acid is cytotoxic to human chronic myelogenous leukemia K-562 (EC50=238 μM), histiocytic lymphoma U-937 (EC50=250 μM), and promielocytic leukemia HL-60 (EC50=476 μM) in RPMI 1640 medium.