Diastereoselective Total Synthesis of Both Enantiomers of Epolactaene

Abstract

A stereocontrolled total synthesis of both the (+)- and (-)-epolactaene ((+)- and (-)-1) enantiomers from tetrahydropyran-2-ol is described. The following reactions in this synthesis are particularly noteworthy: (1) the stereoselective construction of the conjugated (E,E,E)-triene by a combination of kinetic deprotonation and thermodynamic equilibration, (2) the E-selective Knoevenagel condensation of beta-ketonitrile 33 with a chiral 2-alkoxyaldehyde, (3) a diastereoselective epoxidation achieved using a bulky nucleophile (TrOOLi) and an appropriate protecting group, (4) the mild hydrolysis of an alpha-epoxy nitrile by silica gel on TLC facilitated by hydroxyl-mediated, intramolecular assistance.

Synthetic and Structure-Activity Relationship Studies on Bioactive Natural Products

“…Epolactaene is present in a 5:1 tautomeric mixture derived from epimerization at the hemiaminal moiety. The absolute configuration of epoxide in 1 was determined independently by Hayashi 2,3) and Kogen.…”

“…[2][3][4][5][6][7][14][15][16][17] Our group accomplished the total synthesis of epolactaene by a convergent approach utilizing a fluoride anion catalyzed aldol-type reaction of a silyl epoxylactone 3 with a tetraene aldehyde 4 (Scheme 1). [14][15][16] We established large-scale preparation of enantiomerically pure 3, starting from (S)-ethyl lactate (Scheme 2).…”

Convenient synthesis of trifluoromethylated 2-pyrrolidone and 2-pyrrolone derivatives

“…1 H NMR spectra were recorded on a Varian VXR-300 spectrometer and 13 C NMR spectra were recorded on a Varian Mercury-400 spectrometer. 1 …”

“…Among these heterocycles, pyrrolidone, pyrrolone, pyrrolidine play a special role because they are a part of various alkaloids [1][2][3][4]. Although these compounds are in great demand, general methods for their synthesis are absent.…”

Transformation of thiols to disulfides by epolactaene and its derivatives

“…19 We established an efficient synthesis of epolactaene via an oxiranyl anion derived from the a,b-epoxy-c-lactone. [20][21][22][23] Using this synthetic methodology, we prepared several epolactaene derivatives to investigate the structure-activity relationship as well as its biological mechanism of action and to further examine potential new biological activities. In the course of our studies on the chemistry and biology of epolactaene and its derivatives, we found that epolactaene (1a) induce the disulfide formation of N-acetylcysteine methyl ester (2) (Scheme 1).…”