Total Asymmetric Synthesis and Stereochemical Confirmation of (+)- and (−)-Lyoniresinol and Its Deuterated Analogues

Abstract

Lyoniresinol and its derivatives are lignans which have been isolated from a plethora of plant species. In addition to exhibiting a range of interesting biological activities including anticancer, anti-inflammatory, antimicrobial, and others, these compounds have also been discovered in wines and spirits and shown to have gustatory effects in these alcoholic matrices. (+)-Lyoniresinol 1 is reported to impart a strong bitter taste while its enantiomer (−)-lyoniresnol 2 is tasteless. The first total asymmetric synthesis of both natural enantiomers (+)-1 and (−)-2 and their deuterated analogues (D 4 )-(+)-3 and (D 4 )-(−)-4 has been achieved, confirming the structure and stereochemistry of the natural products. The synthesized compounds can be utilized as internal standards in stable isotope dilution analysis for improving and optimizing the existing lyoniresinol quantitation methods in the future.

The enantioselective total syntheses of (+)-7-oxohinokinin, (+)-7-oxoarcitin, (+)-conicaol B and (−)-isopolygamain

“…It should be noted that our approach of using aldol addition of a substituted benzaldehyde, followed by deoxygenation, rather direct alkylation of a benzylic halides was preferred due to the prior experiences of ourselves, and others, who have shown that direct alkylation of a highly electron-rich benzylic halides to be highly problematic and inconsistent. 21,22 Following this retrosynthetic plan, we herein report the synthesis of 1-3 for the first time and in addition, five unnatural lignan derivatives were also accessed using the same strategy by altering the aromatic substitutions with common lignan patterns.…”

“…It should be noted that our approach of using aldol addition of a substituted benzaldehyde, followed by deoxygenation, rather direct alkylation of a benzylic halides was preferred due to the prior experiences of ourselves, and others, who have shown that direct alkylation of a highly electron-rich benzylic halides to be highly problematic and inconsistent. 21,22…”

Total Syntheses and Absolute Stereochemical Correction of Negundin B, Vitexin 1, and Vitexin 6

“…The aldehyde functionality in vitexin 1 was envisaged to be accessed through selective oxidation of an allylic alcohol. − This oxidation could therefore take place from the diol product accessed through reductive cleavage of dihydro-naphthalene lactone 1 . , Lactone 1 was proposed to be formed via acid-catalyzed cyclization of butyrolactone 2 , with subsequent elimination of the C7′ substituent to install the allylic system. This was envisaged to be possible by using an acid-labile protecting group at C7′.…”

“…yield from 4-pentenoic acid and ( S )-4-benzyl-2-oxazolidinone . Initially, isopropyl protected vanillin was chosen as the aldol partner and underwent an anti -aldol addition , to give an 83% yield of aldol 5a with excellent diastereomeric excess ( e.e . > 99%), determined by 1 H NMR (Scheme ).…”

“…Others have similarly reported instability in dihydro-naphthalane diols . Removal of the isopropyl groups using AlCl 3 led to decomposition of diol 12a . Further deprotections were attempted (Table S2); however, diol 12a was deemed unstable so the removal of the isopropyl groups was instead attempted on stable lactone 11a .…”