Total synthesis of (+)-asperlin

Syntheses of (+)-asperlin 1 were achieved via two different synthetic routes. 1,2-Addition of α-furyl anion to (2R,3S)-2-tbutyldimethylsilyloxy-3-chlorobutanal 6 gave (1S,2R,3S)-1-(2-furyl)-2-tbutyldimethylsilyloxy-3-chlorobutanol 7, which was converted to the chiral intermediate, (1S,2R,3R)-1-(2-furyl)-2,3-epoxybutanol 8 (37% overall yield from 6) for the synthesis of (+)-1. The second synthesis of (+)-asperlin 1 from (2R,3S)-6 was achieved in 8% overall yield, based on a combination of the indium-assisted stereoselective addition of 3-bromopropenyl acetate 9 to (2R,3S)-6 and the ring closing metathesis (RCM) using Grubbs catalyst.

Figure optionsDownload as PowerPoint slide

(1S,2R,3R)-1-(2-Furyl)-2,3-epoxybutanolC8H10O3Ee = >99%[α]D24=-42.2 (c 0.67, CHCl3)Source of chirality: lipaseAbsolute configuration: (1S,2R,3R)

(3R,4R,5S,6R)-3-Acetoxy-4-acryloyloxy-5,6-epoxy-1-hepteneC12H16O5Ee = >99%[α]D25=+19.1 (c 0.54, EtOH)Source of chirality: lipaseAbsolute configuration: (3R,4R,5S,6R)