Asymmetric synthesis of (-)-(S,S)-homaline

作者：Davies Stephen G^*; Lee James A; Roberts Paul M; Stonehouse Jeffrey P; Thomson James E

来源：Tetrahedron Letters, 2012, 53(9): 1119-1121.

DOI：10.1016/j.tetlet.2011.12.088

• (-)-(S,S)-Homaline
• Homalium alkaloids
• Lithium amide
• Conjugate addition
• Asymmetric synthesis

The asymmetric synthesis of (-)-(S,S)-homaline was achieved in 8 steps from commercially available starting materials using the diastereoselective conjugate addition of the novel lithium amide reagent lithium (R)-N-(3-chloropropyl)-N-(alpha-methyl-p-methoxybenzyl)amide to methyl cinnamate to install the correct stereochemistry. Subsequent functional group manipulation of the resultant beta-amino ester and Sb(OEt)(3)-mediated macrolactamisation was followed by homodimerisation to give (-)-(S,S)-homaline in 18% overall yield, representing the first asymmetric, and by far the most efficient synthesis of this natural product reported to date.

• 出版日期2012-2-29