Abstract
Two chiral ansa-bridged lactams ([16]metacyclophanes) 2a,b were synthesized starting from 2-methoxyhydroquinone diisopropyl ether (6) in 14 (2a, 3.9% overall) and 16 synthetic steps (2b, 0.6% overall). Both compounds contain typical features of geldanamycin (1) in the C-1 to C-9 part of the ansa chain, i.e. the α,β,γ,δ-unsaturated anilide (C-1 to C-5), the carbamate at the stereogenic carbon atom C-7 and the E-double bond between C-8 and C-9. While the rest of the ansa chain (C-10 to C-15) was an alkyl chain in compound 2a, a more polar CH2OCH2CH2OCH2 chain was installed in compound 2b. Key step of the sequence was a ring-closing metathesis in which the ansa compounds 3 were formed as a mixture of isomers. Deprotection and oxidation to the quinone failed for diisopropyl ether 2b but was successfully conducted with precursor 2a.
Key words
ansamycins - metathesis - protecting groups - quinones - stereoselective synthesis
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