A facile asymmetric synthesis of (+)-eldanolide

The monoterpenoid pheromone (+)-eldanolide, a long range sex attractant, has been synthesized in four steps from the chiral 2,3-epoxy alcohol 4 in 36% overall yield. Our synthetic strategy features the formation of a 1,3-diol by regio- and stereoselective ring opening of 2,3-epoxy alcohol 4, an intermediate easily available from Sharpless asymmetric epoxidation. Other key steps include one carbon elongation, saponification, and lactonization. The present work constitutes a general method for the rapid synthesis of a number of related γ-lactone natural products.

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(2R,3R)-2,3-Epoxy-6-methylhept-5-en-1-olC8H14O2Ee = 93.6% (assumed to be the same as that of its corresponding O-benzoate)[α]D27=+19.15 (c 2.25, CHCl3)Source of chirality: asymmetric epoxidationAbsolute configuration: (2R,3R)

((2R,3R)-3-(3-Methylbut-2-enyl)oxiran-2-yl)methyl benzoateC15H18O3Ee = 93.6% [HPLC: Chiral Delta-S column, hexanes/2-propanol: 100/1, rate: 0.8 mL/min][α]D23=+20.63 (c 1.45, CHCl3)Source of chirality: (2R,3R)-2,3-epoxy-6-methylhept-5-en-1-olAbsolute configuration: (2R,3R)

(2S,3R)-2,6-Dimethylhept-5-ene-1,3-diolC9H18O2[α]D20=+20.6 (c 1.2, EtOH)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

(3S,4R)-4-Hydroxy-3,7-dimethyloct-6-enenitrileC10H17NO[α]D20=-5.4 (c 1.2, EtOH)Source of chirality: (2S,3R)-2,6-dimethylhept-5-ene-1,3-diolAbsolute configuration: (3S,4R)

(+)-EldanolideC10H16O2[α]D20=+48.2 (c 1.15, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,5R)