Phthalides biological activities

Phthalides are valuable synthons for obtaining several biologically active compounds and natural products. Naphthols, anthraquinones and anthraquinone antibiotics, isoquinolones, phthalide isoquinolines, indolizidine and quinolizidine alkaloids, and berbine alkaloids have been synthesised with phthalides as the starting compounds. Some of the syntheses, which have interesting chemistry, are described below. The required phthalides, in some cases, have been synthesised through aromatic lithiation reactions, while in others by more conventional methods. 

CHEMISTRY AND BIOLOGICAL ACTIVITIES OF NATURALLY OCCURRING PHTHALIDES... 

In this article, we review the chemical structures and sources of the currently known naturally occurring phthalides of plant. Recent advances related to the biological activities of the extensively investigated natural phthalides are also described. As examples, we focus on the phthalide ingredients and medical uses of three commonly used phthalide-containing TCM herbs. 

The details of the classifications and chemical structures of four types of natural phthalides are illustrated in Figs. (2-6). Most of the isolated natural phthalides belong to the 3-substituted phthalide type, which accounts for about 61% of the total known naturally occurring phthalides, and of these, non-alkaloid phthalides constitute the most important subtype due not only to their abundance in nature (75 compounds identified) but also their extensively reported pharmacological activities. The pharmacological activities of individual phthalides are discussed in the following Biological Activity Section. 

Table 2. Summary of the Biological Activities of Naturally Occurring Phthalides of Plant Origin...

Chiral 3-substituted phthalides are central structures in a number of biologically active compounds. The synthesis of chiral phthalides has been achieved by Witulski and Zimmerman, starting with enantiopure substituted propargylic alcohols 409 (Scheme 2-38). The chiral ester-linked diyne 410 was cyclotrimerized with acetylene by using RhCl(PPh3)3 as the catalyst to afford enantiopure phthalides 411 in good yields. 

Phthalides are an important class of oxygen-containing heterocycles found in natural products and exhibit a broad spectrum of biological activities [7]. 

---