First Total Synthesis of Lippialactone and Its C9 Epimer

Abstract

This paper describes the first total synthesis of bioactive lippialactone and C9-epi-lippialactone adopting Keck asymmetric allylation/Barbier allylation and olefin cross-metathesis as the key steps.

Key words

lippialactone - 6-substituted α,β-unsaturated δ-lactones - l-threonine - Keck allylation - Barbier allylation - cross-meta­thesis

• References

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• 15 The diastereomeric ratio of 7a/7b was determined by ¹H NMR analysis of the mixture, from the relative integration of the well-resolved, diagnostic protons due to O-CH₂-O (MOM) which resonated in 7a at δ 4.80 (q, J = 6.8 Hz), 4.72 (d, J = 6.8 Hz) and 4.64 (d, J = 6.8 Hz), while in 7b the same protons were observed at δ 4.76 (d, J = 6.8 Hz) and 4.70 (q, J = 7.0 Hz). Further, the O-CH₃ (MOM) protons appeared at δ 3.46 and 3.39 as singlets in 7a, while in 7b the same protons were observed at δ 3.43 and 3.41. The ratio was also confirmed by HPLC analysis {LCMS [column: XDB-C18, 30% H₂O (NH₄OAc, 10 mmol) in MeCN, flow rate: 1 mL/min, 230 nm]: t _R (major) = 3.825 min, t _R (minor) = 4.158 min}.