Caylobolide Tadeusz F. OH OH OH Molinski HO OH OH OH OH 巨大鞘丝藻 HO Lyngbya majuscula A 36-membered macrolactone from Lyngbya majuscula which displayed Cytotoxicity against human colon tumour cell (HCT-116)in vitro was isolated in University of California
Caylobolide A 36-membered macrolactone from Lyngbya majuscula which displayed Cytotoxicity against human colon (结肠) tumour cell (HCT-116) in vitro was isolated in University of California. O HO OH OH OH OH O HO OH OH OH 巨大鞘丝藻 Lyngbya majuscula Tadeusz F. Molinski
三、内酯环含有氧环的大环内酯类 大环内酯类化合物由于在环的结构上含有双键，羟基等， 在次生代谢过程中发生氧化，脱水等化学反应，形成各种含氧 3,5 or 6-membered epoxide rings. H HO H3CO 苔藓虫素 OH OCH3 G.R.Pettit Arizona State Uni. 例：Bryostatin-l(苔藓虫素n Phase-Ⅱtrials)总合草苔虫为海洋底栖动物. 新颖的作用机制：作用于蛋白激酶C(PKC) G.R.Pettit,et al.J.Am.Chem.Soc.,1982,104,6846
新颖的作用机制：作用于蛋白激酶C (PKC) v例：Bryostatin-1 (苔藓虫素 In Phase-II trials) 总合草苔虫为海洋底栖动物. 大环内酯类化合物由于在环的结构上含有双键，羟基等， 在次生代谢过程中发生氧化，脱水等化学反应，形成各种含氧 环 3, 5 or 6-membered epoxide rings. 苔藓虫素 O O O O O H3CO O OH H OH HO O O OCH3 O OH O O H H H H G. R. Pettit, et al. J. Am. Chem. Soc., 1982, 104, 6846. G. R. Pettit Arizona State Uni
Bryostatins 苔藓虫素 In 1968,NCI commissioned a large-scale collection of the bryozoan Bugula neritina by Gulf Specimen Company off the west coast of Florida that was sent to Pettit's group for chemical workup.The aqueous 2-propanol extract was subsequently tested by NCI for its intrinsic activity as an antitumor agent in the then current P-388 and L- 1210 murine leukemia in vivo models. HO H3CO 总合草苔虫 苔藓虫素
Bryostatins • In 1968, NCI commissioned a large-scale collection of the bryozoan Bugula neritina by Gulf Specimen Company off the west coast of Florida that was sent to Pettit’s group for chemical workup. The aqueous 2-propanol extract was subsequently tested by NCI for its intrinsic activity as an antitumor agent in the then current P-388 and L- 1210 murine leukemia in vivo models. O O O O O H3CO O OH H OH HO O O OCH3 O OH O O H H H H 总合草苔虫 苔藓虫素
Total Synthesis Bryostatins 斯坦福大学化学系Paul A.Wender教授 HO H3CO Paul A.Wender AcO 0 Me Me OH Ph NH Me Me OCH3 OH HO H OBz OAc Fourteen tons of Bugula neritina harvested from waters off the coast of California yielded a paltry 18 grams of bryostatin
Paul A. Wender 斯坦福大学化学系Paul A. Wender教授 Total Synthesis Bryostatins O O O O O H3CO O OH H OH HO O O OCH3 O OH O O H H H H Me Me HO Me AcO OBz H Me OAc OH O O O OH Ph NH O O Fourteen tons of Bugula neritina harvested from waters off the coast of California yielded a paltry 18 grams of bryostatin
Bryostatins苔藓虫素 1968年发现总合草苔虫有抗癌活性，1982年以釜野德明Y.Kamano)为 中心的Pettit Group.从采集于加利福尼亚太平洋蒙特内海湾的总合草苔虫 Bugula nertina分得第一个具有抗癌活性的大环内酯类并用X-ray确定了 结构。 HO 1982年Bryostatin-1 1983Bryostatin-2 and 3 (500 Kg material) 1984年Bryostatin-4 1985年Bryostatin-5-8 OCH 1986Bryostatin-9-11 1987Bryostatin-12-13 (1000 Kg) 苔藓虫素 1994-6Bryostatin-14-18 Total 20.Bryostatin-1 and 3 in clinic trial. G.R.Pettit
v1968年发现总合草苔虫有抗癌活性，1982 年以釜野德明(Y. Kamano)为 中心的Pettit Group从采集于加利福尼亚太平洋蒙特内海湾的总合草苔虫 Bugula nertina分得第一个具有抗癌活性的大环内酯类并用X-ray 确定了 结构。 v1982 年Bryostatin-1 v1983 年Bryostatin-2 and 3 (500 Kg material) v1984 年Bryostatin-4 v1985 年Bryostatin-5-8 v1986 年Bryostatin-9-11 v1987 年Bryostatin-12-13 (1000 Kg) v1994-6 年Bryostatin-14-18 vTotal 20. Bryostatin-1 and 3 in clinic trial. 苔藓虫素 O O O O O H3CO O OH H OH HO O O OCH3 O OH O O H H H H G. R. Pettit