Stereoselective Synthesis of Both Enantiomers of Rugulactone

Abstract

The stereoselective total synthesis of both enantiomers of rugulactone 1 has been completed by applying enantioselective allyl additions as key steps. Two different strategies based on highly stable and enantiomerically pure α-substituted allylboronic esters 2 and 3 were performed starting from boronic ester 4.

Rugulactone and its Analogues Exert Antibacterial Effects through Multiple Mechanisms Including Inhibition of Thiamine Biosynthesis

“…Several syntheses of rugulactone have already appeared in the scientific literature. The key step—the introduction of the single chiral centre at C‐6—has been achieved variously by use of a chiral pool approach,5 proline‐catalysed α‐aminooxylation of alcohols,2 Jacobsen′s hydrolytic kinetic resolution of epoxides,6 Keck asymmetric allylation7 or allylation of carbonyl compounds with chiral boronic esters 8. In our syntheses of rugulactone and of probes, we utilized asymmetric catalytic Overman esterification9 as the crucial step (Scheme S1 in the Supporting Information).…”

Recent Advances in the Stereoselective Total Synthesis of Natural Pyranones Having Long Side Chains

“…The compound was found to inhibit constitutive NF-kB activity in human lymphoma cell lines. Several syntheses of rugulactone (48) have recently been reported [38][39][40][41][42][43][44][45][46][47][48]. In these syntheses, the chirality has been introduced by applying different methodologies such as Jacobsen's hydrolytic kinetic resolution of epoxides, Keck/Maruoka asymmetric allylation, chemoenzymatic process, the chiral pool approach, and allylation with chiral boronic esters.…”

“…The intermediate 81 was prepared by Barua et al [45] from the chiral epoxide 82 (Scheme 17) and by Pietruszka et al [46] from the allylic boronic ester 85 (Scheme 18). In a synthetic approach, Reddy and Singh [48] applied Sharpless asymmetric epoxidation of an allyl alcohol to generate a chiral alcohol, which was applied as a key intermediate.…”

A Facile Stereoselective Total Synthesis of (R)-Rugulactone

“…The biological assays of 6-arylalkyl-5,6-dihydro-2H-pyran-2-one, ( R )-rugulactone ( 1 ), which has been extracted from the evergreen tree Cryptocarya rugulosa [13] of Lauraceae family, have been found to inhibit the nuclear factor (NF- κ B) activation pathway occurring in different types of cancers [14–18]. Due to the attractive biological activity of ( R )-rugulactone ( 1 ) (Figure 1), several total syntheses have already been reported in the literature [19–25]. In those reported syntheses the chiral center was created by different means: by Jacobsen's hydrolytic kinetic resolution of epoxides [19], by Keck's asymmetric allylation [21], by proline catalyzed α -aminoxylation [22] of aldehydes, by enzymatic resolution of racemic homoallylic alcohols [23], and by using a chiral pool [24, 25].…”

“…Due to the attractive biological activity of ( R )-rugulactone ( 1 ) (Figure 1), several total syntheses have already been reported in the literature [19–25]. In those reported syntheses the chiral center was created by different means: by Jacobsen's hydrolytic kinetic resolution of epoxides [19], by Keck's asymmetric allylation [21], by proline catalyzed α -aminoxylation [22] of aldehydes, by enzymatic resolution of racemic homoallylic alcohols [23], and by using a chiral pool [24, 25]. In this communication, we describe the stereoselective synthesis of ( R )-rugulactone starting from inexpensive starting materials.…”