Camptothecin (hereinafter, referred to as CPT) is a pentacyclic alkaloid isolated from natural materials such as Camptotheca acuminata, Nyssaceae, which is native to China. Various effective semi-synthetic derivatives having anti-tumor activity prepared using CPT as a starting material have been provided from searching studies by the present inventors and others.
CTP-11, which is a hydrochloride trihydrate of 7-ethyl-10-[4-(1-piperidino)-1-iperidino]carbonyloxycamptothecin (hereinafter, referred to as SN-38B-11) derivatized from CPT, is a compound having high anti-tumor activity with low toxicity, and CPT-11 is widely sold as an anti-tumor agent (general name: irinotecan hydrochloride) at present.
However, since the amount of CPT that can be obtained from a natural material such as Camptotheca acuminata, which is a raw material, is extremely small, it is anticipated that it will become difficult to supply a sufficient amount of CPT as the demand of CPT-11, which is its effective derivative, increases, although means to procure the raw material including planting has been taken. Furthermore, since CPT-11 is prepared from a naturally-derived extract after isolation and purification, a difference in raw materials such as Camptotheca acuminata and Nothapodytes foetida may cause the inclusion of different impurities. Thus, when Nothapodytes foetida is used as the raw material, the extract contains 18,19-dehydrocamptothecin represented by a formula (1):
at a rate of several percent relative to CPT (refer to Patent document 1, Non-patent document 1). Regarding vinyl-form compounds having a vinyl group such as 18, 19-dehydrocamptothecin, the vinyl group remains in the subsequent production processes of CPT-11 as shown below, and the vinyl form cannot be completely removed by silica-gel column chromatography and others in any of the subsequent processes; therefore, it was difficult to obtain CPT-11 with high purity, when Nothapodytes foetida was used as the raw material.

Meanwhile, the problem of impurities will be solved when total synthesis is used; however, the preparation process by total synthesis has many problems in terms of equipment, yield and cost, so that the practical application has not yet been achieved.    [Patent document 1] JP, A, 64-61482    [Non-patent document 1] R. Aiyama, et al., Phytochemistry, Vol. 27, No. 11, pp. 3663-3664, 1988.