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

• Published in: Journal of natural products (Washington, D.C.) Vol. 68; no. 11; pp. 1603 - 1609
• Main Authors: Lassen, Peter R, Skytte, Dorthe Mondrup, Hemmingsen, Lars, Nielsen, Simon Feldbæk, Freedman, Teresa B, Nafie, Laurence A, Christensen, S. Brøgger
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01-11-2005; Glendale, AZ American Society of Pharmacognosy
• Subjects: Animals; Antimalarials - chemical synthesis; Antimalarials - chemistry; Antimalarials - pharmacology; Biological and medical sciences; Circular Dichroism; General pharmacology; Lignans - chemical synthesis; Lignans - chemistry; Lignans - pharmacology; Medical sciences; Molecular Structure; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Phenols - chemical synthesis; Phenols - chemistry; Phenols - pharmacology; Plasmodium falciparum - drug effects; Stereoisomerism; Antimalarial; Pharmacognosy; Theoretical study; Modeling; Vibrational circular dichroism; Biological activity; Total synthesis; Infrared spectrometry; Antiprotozoal agent; Enantiomer; Circular dichroism spectrometry; Absolute configuration; Molecular model; Force field method; Parasiticide; S configuration; Lignan; Chemical synthesis; Comparative study; Structural analysis; Conformation
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np0502995

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.