Entry into Major Groups Retaining Taxol via Sinenxan A

Compound 1 as a key intermediate of 1, 7, 9-trideoxytaxol was synthesized in ten steps from a biosynthetically available taxane, Sinenxan A. The key steps in the synthesis were deoxygenation at C-14, allylic oxidation at C-13 and construction of the oxetane ring.

A Taxatetraene from Microbial Transformation of Sinenxan A

Sinenxan A [2α, 5α, 10β, 14β-tetraacetoxytaxa-4(20), 11-diene, 1] was biotransformed by a filamentous fungus, Aspergillus niger JCM 5546, and an unusual taxatetraene [2α, 5α-acetoxytaxa-4(20), 10(11), 12(18), 13(14)-tetraene, 2], together with two known products, 10β-deacetyl sinenxan A (3) and 10β, 14β-dideacetyl sinenxan A (4) were produced.

Chemistry of Taxoid Sinenxan A: (Ⅰ) Epimerization of the 14β-hydroxyl Group

Compound 2 with 14β-hydroxyl group was successfully converted into its epimerized α-counterpart via oxidation - reduction.The elimination product (6) was auto-oxidized to epoxide 8,even in the solid state

Reactivity of C-10 Function in Sinenxan A and Its Derivatives

The allylic nature of C-10 in sinenxan A (1) leads to facile SN1 and eliminion reactions

红豆杉愈伤组织中sinenxans高产细胞系的选择及其培养

目的：对国产红豆杉愈伤组织中的ｓｉｎｅｎｘａｎｓ高产细胞系进行选择及培养，为半合成类紫杉醇抗癌药提供充足的前体化合物。方法：红豆杉培养细胞采用平板培养及二分法继代培养，应用高效液相色谱法测定培养物中的ｓｉｎｅｎｘａｎｓ含量，选择出ｓｉｎｅｎｘａｎｓ高产细胞系并扩大培养。结果：Ｓｉｎｅｎｘａｎｓ的含量在不同种红豆杉的愈伤组织及同种不同无性系间存在明显的差异，并与培养物的色泽有一定的相关性；不同的培养基组成与培养方式对高产细胞系的生长有较大影响；获得了一个ｓｉｎｅｎｘａｎｓ高产细胞系Ｔｓ１９，其ｓｉｎｅｎｘａｎｓ含量达细胞干重的４．０％；在一个培养周期中，Ｔｓ１９组织培养物生长缓慢，ｓｉｎｅｎｘａｎｓ的含量在培养前期有所下降，而在培养后期可达到最高水平。结论：在一定的培养条件下，选择出的ｓｉｎｅｎｘａｎｓ高产细胞系的ｓｉｎｅｎｘａｎｓ含量稳定。

紫杉烷类多药耐药逆转剂的合成及其逆转耐药活性

目的 设计合成一系列新型紫杉烷类化合物并进行逆转多药耐药肿瘤细胞耐药活性的筛选。方法 以本所生物合成的紫杉烷 ,SinenxanA为原料 ,合成了 1 0个 (I1～ 7,II1 ,2 ,III)新的紫杉烷类化合物 ,其结构经FABMS ,2DNMR确证 ,并对多药耐药癌细胞进行了逆转耐药性的试验。结果 9个 (I2～ 7,II1 ,2 ,III)化合物对多药耐药的人口腔上皮癌细胞KB V2 0 0 ,能够显著逆转其耐药性 ,增强抗癌药的活性 ,其中化合物I2 ,I3 ,I4逆转活性明显好于已知对照药Verapamil。结论 紫杉烷类化合物作为多药耐药逆转剂有较好的逆转耐药活性 。