Novel stereoselective syntheses of N-octyl-β-valienamine (NOV) and N-octyl-4-epi-β-valienamine (NOEV) from (−)-shikimic acid

Abstract

N-Octyl-β-valienamine (NOV) 1 and N-octyl-4-epi-β-valienamine (NOEV) 2 are potent chemical chaperone drug candidates for the therapy of lysosomal storage disorders. Novel stereoselective syntheses of NOV 1 and NOEV 2 starting from naturally abundant (−)-shikimic acid are described in this article. The common key intermediate compound 5 was first synthesized from readily available (−)-shikimic acid via 9 steps in 50% yield. Compound 5 was then converted to NOV 1 via 5 steps in 61% yield, and it was also converted to NOEV 2 via 8 steps in 38% yield. In summary, NOV 1 was synthesized via 14 steps in 31% overall yield; and NOEV 2 was synthesized via 17 steps in 19% overall yield.