Synthetic Studies towards NG-121: Diastereoselective Synthesis of NG-121 Methyl Ether

Abstract

Starting from unsymmetrically O-protected methyl 4-bromo-3,5-dihydroxybenzoate, a facile synthesis of the methyl ether of bioactive natural product NG-121 was accomplished in very good overall yield. The key steps were: Stille coupling reaction of the farnesyl unit with the electron-rich phenolic segment; hydroxy-directed selective epoxidation of the farnesyl chain along with concomitant phenol-driven intramolecular regio- and diastereoselective ring closure to the corresponding hydroxybenzopyran; and regioselective formylation followed by in situ reductive lactonization.

Key words

4-bromo-3,5-dihydroxybenzoate - Stille coupling - intramolecular cyclization - formylation - lactonization - NG-121 methyl ether

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