Addition of methyl thioglycolate and benzylamine to (Z)-ligustilide, a bioactive unsaturated lactone constituent of several herbal medicines. An improved synthesis of (Z)-ligustilide.
(Z)-Ligustilide [1] is a dihydrophthalide purported to be the active ingredient of Ligusticum plant species widely used as herbal medicines in the Orient and in Native American and Hispanic cultures. It readily underwent 1,6-conjugate addition with methyl thioglycolate in the presence of triethylamine. The methyl thioglycolate reaction also yielded a product from addition to the C-6-C-7 double bond and a diadduct from both 1,6-addition and addition to the C-6-C-7 bond. Reaction of 1 with benzylamine did not afford a 1,6-adduct, but yielded instead an N-benzyllactam, presumably formed by rearrangement from initial 1,2-addition to the carbonyl. An improved total synthesis of 1 was developed. (Z)-Ligustilide had weak antiviral properties and weak antimicrobial activity against Gram-positive, Gram-negative, and yeast microorganisms. The broad biological activity of 1 and its electrophilic reactivity are consistent with the use of Ligusticum species in folk medicine.
Beck
J J
JJ
Department of Chemistry, Colorado State University, Fort Collins 80523, USA.
Stermitz
F R
FR
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000890:Anti-Infective Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D001596:Benzylamines / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013864:Thioglycolates / Q000737:chemistry
D000890:Anti-Infective Agents; D000998:Antiviral Agents; D001596:Benzylamines; D013864:Thioglycolates; C027820:ligustilide; D015107:4-Butyrolactone