Efficient Enantioselective Hetero-Diels−Alder Reaction of Brassard's Diene with Aliphatic Aldehydes:  A One-Step Synthesis of (R)-(+)-Kavain and (S)-(+)-Dihydrokavain

Abstract

An efficient catalytic asymmetric hetero-Diels-Alder reaction of Brassard's diene with aliphatic aldehydes was reported. The catalyst, which was generated from (R)-BINOL, Ti(i-PrO)4, and 4-picolyl chloride hydrochloride, promoted the reaction smoothly to afford the corresponding alpha,beta-unsaturated delta-lactone derivatives in moderate-to-good yields (46-79%) with high enantioselectivities (up to 88% ee). Natural products (R)-(+)-kavain (70% ee, >99% ee after single recrystallization) and (S)-(+)-dihydrokavain (84% ee) were also prepared in one step by using this methodology.

Identification and Characterization of Kava‐derived Compounds Mediating TNF‐α Suppression

“…Thus, the various derivatives of kava extract collectively display an array of inhibitory and activating effects on the NF‐ κ B signaling pathway that provide one potential starting point for elucidating the molecular mechanism(s) underlying the TNF‐ α suppression effects of specific family members. Although there are numerous synthetic approaches to kavalactones (37–42), despite the compelling biological activities reported for this class of compounds no systematic medicinal chemistry optimization program has been described.…”

Solid-Phase Biomimetic Synthesis of Polyketide

“…The enantiomeric ratio was determined by HPLC analysis (Chiralpak AD-H, hexane/2-propanol = 90:10, 1.0 mL min –1 ): t R = 18.1 min (major) and 20.7 min (minor). The absolute configuration of the major enantiomer was determined by comparing with the literature data . [α] D 26 + 81.5 ( c = 0.1, EtOH).…”

“…S-Dodecyl (S)-2-Hydroxy-3-phenylpropanethioate (24). To a solution of (S)-3-phenyllactic acid (828.7 mg, 4.987 mmol) in DMF (16.6 mL), CDI (808.5 mg, 4.986 mmol) was added at 0 °C, and the reaction mixture was stirred for 30 min at this temperature.…”

“…The absolute configuration of the major enantiomer was determined by comparing with the literature data. 24 [α] D 26 + 81.5 (c = 0.1, EtOH).…”

De novo biosynthesis of diverse plant-derived styrylpyrones in Saccharomyces cerevisiae

“…Additionally, the complexity of plant extracts hinders efficient styrylpyrone isolation and production, which hinders the investigation of their pharmacological effects. While chemical synthesis is an alternative solution for the production of plant natural products (PNPs), only a few kavalactones and their derivatives have been chemically synthesized at laboratory scales with yields ranging from 30% to 60% ( Ali Shaik et al, 2012 ; Israili and Smissman, 1976 ; Kraus and Wanninayake, 2015 ; Lin et al, 2008 ; Volgin et al, 2020 ). The poor stereospecificity and the involvement of heave metals as catalysts further hinders large-scale chemical synthesis.…”