Enantioselective Formal Synthesis of Eleuthesides

Abstract

An intramolecular Diels-Alder reaction of an enantiopure 3,5-hexadienyl acrylate and a chemoselective epimerization constitute the key steps of a highly stereoselective synthesis of triol 25, whose conversion to eleutherobin, eleuthosides A and B and sarcodictyins A and B is known.

antitumor agents - stereoselective addition reactions - organometallic reagents - intramolecular Diels-Alder reactions - chemoselective epimerization

References

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The relative configuration of 8 and 9 was elucidated by a NOESY experiment with acetonide A (Figure [2] ) prepared from 8/9 by desilylation (40% HF, MeCN, r.t., 90% from 8, 78% from 9) and subsequent acetalization of the resulting single diol (acetone, PPTS, r.t., 91%).

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Upon changing the lactaldehyde protecting group to TBDPS, [8b] silyl migration was slightly diminished, while complete Felkin-Anh selectivity of addition was maintained. However, the corresponding products were less readily separated. With MOM protection [8c] the diastereo-selectivity of addition was too low for synthetic utilization. Transmetalation from Li to Al (Me₂AlCl) or Mg (MgBr₂ etherate) gave less 8/9.

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<A NAME="RG24203ST-21">21</A>

Compound 25: [α]_D ²⁵ +41.6 (c 0.6, CHCl₃); ref. [2b] [α]_D ²⁵ +43.5 (c 0.2, CHCl₃).