Chemo-enzymatic synthesis of both enantiomers of rugulactone

A Facile Stereoselective Total Synthesis of (R)-Rugulactone

“…The remaining task was to couple the fragment 5-phenyl-pent-1-en-3-one [36] 12 and lactone 11 (3 : 1 ratio) by cross metathesis [37–39], which was implemented by refluxing them in CH 2 Cl 2 in presence of Grubb's second generation catalyst [40] (5 mol%) to deliver enantiomerically pure ( R )-rugulactone ( 1 ) in 74% yield as colorless oil, $\begin{array}{c}{{false[\alpha false]}_{\text{D}}}^{\mathrm{normal25}}\end{array}\text{:}$ −46.2 ( c 1, CHCl 3 ), Lit [41]$\begin{array}{c}{{false[\alpha false]}_{\text{D}}}^{\mathrm{normal25}}\end{array}\text{:}$ −46.9 ( c 1, CHCl 3 ) (see Scheme 3). …”

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.…”

“…Finally, by treatment of this ketone (64) with Grubb's first-generation catalyst, rugulactone (48) was formed. In a chemoenzymatic synthetic approach, both (R)-and (S)-rugulactone were prepared by applying the Candida rugosa lipase to hydrolyze the butyrate ester of the protected 3-hydroxy homoallylic alcohol 65 (Scheme 13) [42]. The key intermediates (R)-66 (ee > 99%) and (S)-67 (ee > 98%) were obtained with high enantiomeric purity.…”

Stereoselective Total Synthesis of Rugulactone

“…Na 2 SO 4 ). Evaporation of the solvents gave the crude alcohol, which was purified by CC to afford the pure alcohol 4 (1.74 g, 87% (6). To the suspension of LiAlH 4 (0.2 g, 5.22 mmol) in dry THF (16 ml) under N 2 at 08 was added 4 (1.5 g, 5.22 mmol) in dry THF (35 ml), and the mixture was stirred at r.t. for 3 h. The mixture was cooled to 08, diluted with Et 2 O, and the reaction was quenched with sat.…”