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Enhanced yield of medicinal products from Tripterygium cell cultures Samija, Mijo Daniel

Abstract

The growth of cell suspensions of the Asian medicinal plant Tripterygium wilfordii was manipulated in order to produce large amounts of pharmacologically active diterpene and triterpene natural products. A method was developed where elicitation with a strain of the fungus Botrytis stimulated the production of oleanane and friedelane triterpene acids. In rapidly growing twelve liter bioreactor cultures, triterpene yields were increased five to ten fold with this process, routinely providing more than 25 mg/L each of 22α-hydroxy-3-oxoolean-12-en-29-oic acid (B) and 3β,22α-dihydroxyolean-12-en-29-oic acid (D) and more than 5 mg/L each of 22β-hydroxy-3-oxoolean-12-en-29-oic acid (A) and 3β,22β-dihydroxyolean-12-en-29-oic acid (C). Yield improvement for the triptolide family of diterpenes (triptolide and tripdiolide) was approached through the synthesis of potential intermediates of the natural biosynthetic pathways, the first step in a technique where synthetic elaborations would be completed by cell cultures. These synthetic intermediates were also sought to establish the details of triptolide biosynthesis. Advances were made towards the synthesis of one potential intermediate, 18(4→ 3)-isodehydroabietenolide, starting from (L)-dehydroabietic acid....(more text)

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