Recent advances in natural phthalides: Distribution, chemistry, and biological activities

An Underutilized Food “Miwu”: Diet History, Nutritional Evaluations, and Countermeasures for Industrial Development

“…Phthalides, a class of ester derivatives bearing a benzene ring fused to a five-membered lactone ring, belong to o-hydroxymethylbenzoic acid lactone [ 42 ]. It is characterized by small molecular polarity, volatility, and instability and is a typical representative component of volatile oil from CX [ 43 ].…”

Oxidative aromatization mechanism of ligustilide

“…7 It generates various dimers and trimers through 2+2 or 4+2 cycloaddition 8 and its aromatic species butylidenephthalide (2) also participates in the polymerization (Scheme 1). 9,10 To date, more than 70 polymers derived from 1 have been found in nature, 1,2 which are also bioactive constituents of Traditional Chinese Medicines. 4,6 The aromatization phenomenon is universal in phthalides, 11,12 which increases the structural diversity of phthalides and may contribute to their bioactivities such as antioxidant, yet its chemical reaction mechanism is unclear.…”

“…For the triplet oxygen, the oxidation should be stepwise because the spins of the two unpaired electrons are mismatched, and a spin flip is needed to form the singlet ground state of compound 2. The spin flip can take place either at triplet diradical complex 3 A, which is generated by a triplet diradical hydrogen abstraction (TDHA) of 1, to produce the singlet diradical complex 1 A, which undergoes a singlet diradical hydrogen abstraction (SDHA) to deliver singlet compound 1 2 and H 2 O 2 , or at triplet compound 3 2, which is formed by two successive TDHAs. In contrast, for singlet oxygen, the oxidation may be a concerted process with no intermediate.…”

“…In contrast, for singlet oxygen, the oxidation may be a concerted process with no intermediate. In this work, we performed density functional theory (DFT) calculations to investigate the above aromatization mechanisms of ligustilide (1).…”

“…At this stage, one of the two unpaired electrons in intermediate 3 A is much more likely to reverse its spin to form singlet intermediate 1 A, whose free energy is only 0.2 kcal mol À1 higher than the former and which undergoes a barrierless SDHA process to produce singlet 1 2 and H 2 O 2 highly exothermally. Nucleus-independent chemical shift (NICS) calculations indicated that states 3 A and 1 A are antiaromatic while compound 1 2 is aromatic (Table S2, ESI †). This conforms to Baird's rule 16 and explains the barrierless SDHA.…”