358778-59-3

Upstream product

• 156127-34-3 taxuyunnanin C 

Relevant academic research and scientific papers

Regio- and stereo-selective biotransformation of 2α,5α,10β,14β-tetra-acetoxy-4(20), 11-taxadiene by Ginkgo cell suspension cultures

Ginkgo biloba cell suspension cultures were used to bioconvert sinenxan A, 2α,5α,10β,14β-tetra-acetoxy-4(20), 11-taxadiene, a taxoid isolated from callus tissue cultures of Taxus spp. Besides two major products, 9α-hydroxy-2α,5α,10β,14β-tetra-acetoxy-4(20

Molecular cloning and characterization of a cytochrome P450 taxoid 9a-hydroxylase in Ginkgo biloba cells

Taxol is a well-known effective anticancer compound. Due to the inability to synthesize sufficient quantities of taxol to satisfy commercial demand, a biotechnological approach for a large-scale cell or cell-free system for its production is highly desirable. Several important genes in taxol biosynthesis are currently still unknown and have been shown to be difficult to isolate directly from Taxus, including the gene encoding taxoid 9α-hydroxylase. Ginkgo biloba suspension cells exhibit taxoid hydroxylation activity and provides an alternate means of identifying genes encoding enzymes with taxoid 9α-hydroxylation activity. Through analysis of high throughput RNA sequencing data from G. biloba, we identified two candidate genes with high similarity to Taxus CYP450s. Using in vitro cell-free protein synthesis assays and LC-MS analysis, we show that one candidate that belongs to the CYP716B, a subfamily whose biochemical functions have not been previously studied, possessed 9α-hydroxylation activity. This work will aid future identification of the taxoid 9α-hydroxylase gene from Taxus sp.

Biotransformation of 2α,5α,10β,14β-tetra-acetoxy-4(20), 11-taxadiene by Ginkgo cell suspension cultures

Ginkgo biloba cell suspension cultures were used to biotransform 2α,5α,10β,14β-tetra-acetoxy-4(20),11-taxadiene. Two novel compounds were obtained and their structures were identified as 9α-hydroxyl-2α,5α,10β,14β-tetra-acetoxy-4(20), 11-taxadiene 1 and 9α, 10β-dihydroxyl-2α,5α,14β-tri-acetoxy-4(20), 11-taxadiene 2, respectively, on the basis of their physical and chemical data. Compound 1 was subsequently used as a substrate for the bioconversion by Ginkgo cell cultures, and the product obtained was confirmed to be the same as 2, which suggested that 2 is biosynthesized from 1. Investigation on properties of the related enzymes responsible for the biotransformation reaction through the experimental techniques of cell-free culture and substrate/product concentration analysis revealed that the enzymes were extracellular and constitutive.

Synthesis and structure-activity relationships of taxuyunnanine C derivatives as multidrug resistance modulator in MDR cancer cells

A series of new generation taxoids bearing a bulky group on different positions such as C-2, C-5, C-7, C-9, C-10 or C-14 were obtained by chemical modifications and biotransformation of taxuyunnanine C (1) and its analogs, 4, 5, and 10. Compounds 3, 5, 6, 8, and 9a showed significant activity toward calcein accumulation in MDR 2780AD cells. The most effective compound 9a with a cinnamoyloxy group at C-14 and a hydroxyl group at C-10 was actually efficient for the cellular accumulation of the anticancer agent, vincristine, in MDR 2780AD cells. The enhancing effects of 6 and 9a for taxol, adriamycin, and vincristine were at the same levels as those of verapamil toward MDR 2780AD cells. Thus, compounds 6 and 9a can modulate the multidrug resistance of cancer cells. The cytotoxicity (IC50) of the compounds was examined against human normal cell line, WI-38, and cancer model cell lines, VA-13 and HepG2. Since compounds 6 and 8 had no cytotoxicity, they were expected to be lead compounds of MDR cancer reversal agents. On the contrary, compounds 3, 5, and 9a showed cell growth inhibitory activity toward VA-13 and/or HepG2 as well as accumulation activity of calcein and/or vincristine in MDR 2780AD and they were expected to be lead compounds of new-type anticancer agents.

Combined biotransformations of 4(20),11-taxadienes

Taxuyunnanine C (1) and its analogs (2 and 3), the C-14 oxygenated 4(20), 11-taxadienes from callus cultures of Taxus sp., were regio- and stereo-selectively hydroxylated at the 7β position by a fungus, Abisidia coerulea IFO 4011, and it was interesting that the longer the alkyl chain of the acyloxyl group at C-14 became, the higher the yield of 7β-hydroxylated product was. Besides the three 7β-hydroxylated products (5, 9, 17), other nine new products (7, 11, 12, 14, 15, 16, 18, 20 and 21) and six known products (4, 6, 8, 10, 13 and 19) were obtained. Subsequently, the acetylated derivatives (24 and 27) of 7β-and 9α-hydroxylated products of 1 were regio- and stereo-specifically hydroxylated at the 9α position by Ginkgo cells and 7β position by A. coerulea, respectively. Thus, the two specific oxidations have been combined. These bioconversions would provide not only valuable intermediates for the semi-synthesis of paclitaxel or other bioactive taxoids from 1 and its analogs, but also some useful hints for the biosynthetic pathway of taxoid in the natural Taxus plant.

Substrate specificity for the hydroxylation of polyoxygenated 4(20),11-taxadienes by Ginkgo cell suspension cultures

Three C-14 oxygenated taxanes isolated from callus cultures of Taxus spp., 2α,5α,10β,14β-tetra-acetoxy-4(20),11-taxadiene 3, 2α,5α,10β-triacetoxy-14β-propionyloxy-4(20),11- taxadiene 4, 2α,5α,10β-triacetoxy-14β-(2-methylbutyryl)-oxy-4(20), 11-taxadiene 5, and three deacetylated derivatives of 3, 10β-hydroxy-2α,5α,14β-triacetoxy-4(20),11-taxadiene 6, 14β-hydroxy-2α,5α,10β-triacetoxy-4(20),11-taxadiene 7, 10β,14β-dihydroxy-2α,5α-diacetoxy-4(20),11-taxadiene 8, could all be regio- and stereo-selectively hydroxylated at the 9α-position by Ginkgo cell suspension cultures to yield a series of new 9α,14β-dihydroxylated taxoids. The effects of functional groups, especially at C-14 of the substrates, on the biotransformation were also investigated. The results revealed that substrates with an acetoxyl group at C-14 could be more efficiently 9α-hydroxylated than those with a longer ester chain or a hydroxyl group at C-14. An acetoxyl or hydroxyl group at C-10 had no effect on the conversion rates of the substrates, but substrates with the hydroxyl group (compared with the acetoxyl analogues) could be converted into 9α-hydroxylated products more easily.