Triptolide isolation

Triptolide, isolated from the herb Tripterygium wilfordii Hook F, has anti-inflammatory and immunosuppressive activities, and... 

Kupchan et al. [38] first isolated triptolide, a highly oxygenated diterpene from an ethanol ic extract of the Chinese medicinal plant Triptergium... 

The unusual triepoxide triptolide (33) was first isolated from Tripterygium wilfordii Hook F. or the thunder god vine by the late Morris Kupchan as part of his systematic investigation of natural products as potential anticancer agents. T. iDilfordii is used in traditional Chinese medicine for the treatment of arthritis and related... 

Other activities of triptolide and of T. ivilfordii extracts are discussed in a recent review these include immunosuppressive and anti-inflammatory effects as well as antiproliferative effects. The potential as well as the chemical complexity of triptolide have led to several synthetic approaches to the compound but current supplies are still provided by isolation from T. wilfordii. Some investigations of plant tissue culture production methods have been carried out " but this approach is not yet practical on a large scale, so compound supply could be an issue in the event that PG490-88 or a related compound is approved for clinical use. Triptolide is thus a versatile lead compound and it will be interesting to find out if its diverse activities lead to clinical benefits to cancer patients. 

Triptolide can be found in all parts of the plant roots, stems and leaves. The content of 1, 2 and 4 depends upon the growth area, age and size of the plant. The yield of 1 from the roots or from the leaves is usually around 10 ppm [21, 27]. One isolation method begins with alcohol extraction, followed by a chloroform extraction and finally use of repeated silica gel column separation to obtain compound 1 and other diterpenoids [26],... 

The first natural optically active triptolide was synthesized starting with the natural /-dehydroabietic acid 93 [76], which is isolated from natural gum rosin [77]. Natural product 93 was oxidized by... 

In 1972, Kupchan et al. isolated the novel diterpenoid triepoxides, triptolide, tripdiolide, and triptonide from the roots of T. wilfordii with strong antileukemic activity [108]. Most recently, crude extracts and refined extracts (a so-called multi-glycoside extract, or GTW) have been used increasingly in clinical treatment of rheumatoid arthritis, ankylosing spondylitis, and a variety of dermatological disorders [90, 91, 109]. 

The isolation of these antileukemic compounds encouraged Kutney and coworkers [173, 174] to develop a plant cell culture line of T. wilfordii that would hopefully produce these compounds in higher yield and under laboratory controlled conditions. In this line, this group have published that the stable cell line, coded as TRP4a, was shown to produce the cytotoxic diterpene triptolide (79) and tripdiolide (80) in yields that were 3 and 16 times greater, respectively, than those observed in the parent plant source. 

In the past 20 years hundreds of Chinese traditional and herbal medicines with immunomodulating functions have been screened, and their active components studied. Through these studies, six diterpene lactone epoxide compounds, with antiinflammatory and immunosuppressive actions, were isolated from T. wilfordii. Zheng et al. [183] assayed the half-effective dose (ED50), the therapeutic index (TI) and a certain safety factor (CSF) using croton oil induced ear swelling and hemolysin-antibody formation mouse models and found that triptolide (79), tripdiolide (80), triptonide (81), tripchlorolide (92), and triptolidenol (93) possessed both antiinflammatory and immunosuppressive activities, while triptriolide (94) showed antiinflammatory action only. Fig. (28). The results of the TI and CSF of both activities clearly demonstrated that the antiinflammatory and immunosuppressive compounds in T. wilfordii are pluralistic and the differences in these compounds can be used as a base for the evaluation and selection of them. 

Jatrophone, 22, also has a broad antitumor spectrum and has been of interest in the NCI program (586). Tripdiolide, 23, and related compounds such as triptolide, 24, have also been of interest as antitumor agents in the NCI program (283). Four novel furanoditerpenes of the entclerodane type, plaunol B (25), C (26), D (27), and E (28) have been isolated from Croton sublyratus and show interesting activity against Shay-induced ulcers in rats at 3-10 mg/kg (552). 

---