Structure and Absolute Configuration of Nyasol and Hinokiresinol via Synthesis and Vibrational Circular Dichroism Spectroscopy

Abstract

The absolute configuration of the norlignan (+)-nyasol was determined to be S by comparison of the experimental vibrational circular dichroism data with first-principle calculations taking into account the eight lowest energy conformations. The established absolute configuration of (+)-nyasol enables establishment of the absolute configuration of (-)-hinokiresinol, which is concluded to be S. A total synthesis and resolution of hinokiresinol has been performed to resolve the conflicting reports of the coupling constant of the vinylic protons of the disubstituted double bond in this molecule. Racemic hinokiresinol was resolved. Both enantiomers possess the same antiplasmodial activity.

Vibrational Circular Dichroism: A New Tool for the Solution-State Determination of the Structure and Absolute Configuration of Chiral Natural Product Molecules

“…The two natural norlignans, nyasol (9) and hirekiresinol (10) have been isolated from a number of natural sources, including Asparagus africanus, and possess the typical C 6 C 5 C 6 backbone structure shown in Figure 11. The AC of (+)-nyasol (9) was determined to be S using VCD, which in turn allowed the absolute configuration of ( − )-hirekiresinol (10) to be assigned as S owing to their synthetic and stereochemical relationship as E-stereoisomers [51]. This work has cleared up ambiguities in the literature regarding the absolute configuration of these molecules.…”

Simple and Convenient Synthesis of (±)-Bakuchiol

“…The key intermediate was prepared by adding citral (2) to a solution of vinylmagnesium bromide and a suspension of cuprous iodide in THF with 63% yield [7]. Together with the product 3, a by-product was isolated and characterized as the 1,2-addition product.…”

Progress in the Chemistry of Organic Natural Products 100

“…Thus, low-resolution neutron studies combined with H 2 O/D 2 O contrast variation were used successfully to trace detergent regions surrounding membrane protein molecules in single crystals (288) for OmpF porin from Escherichia coli (289,290), and the Rhodobacter sphaeroides photochemical reaction center (291) as well as to locate detergents in a lipase-colipase complex (292).…”

“…Optically active antipodes of the nyasol norlignans (+)-229 and (-)-230, naturally occurring in Asparagus africanus and Anemarrhena asphodeloides, respectively, were given absolute configuration assignments by VCD spectroscopy (290). The conformational search of (S)-nyasol using MMFF force field and two DFT methods: B3LYP/6-31G(d,p) and B3LYP/AUG-cc-pVDZ, provided eight stable conformers, within 2 kJ/mol, from 26 found in the initial exploration.…”