A facile and efficient synthesis of some (6E)-hydroximino-4-en-3-one steroids, steroidal oximes from Cinachyrella spp. sponges.
Using beta-sitosterol as a starting material, (6E)-hydroximino-24-ethylcholest-4-en-3-one (1), a natural steroidal oxime from Cinachyrella alloclada and C. apion, was synthesized in four steps with a high overall yield. First, beta-sitosterol (5a) is transformed into the corresponding 24-ethylcholest-4-en-3,6-dione (6a) via oxidation with pyridinium chlorochromate (PCC). Selective reduction of 6a by NaBH(4) in the presence of CoCl(2) gives 24-ethylcholest- 4-en-3beta-ol-6-one (7a). The reaction of 7a with hydroxylamine hydrochloride offers the oxime 8a and the oxidation of 8a by Jones reagent gives the target steroid 1. (6E)-Hydroximinocholest-4-en-3-one (2) and (6E)-hydroximino-24-ethylcholest-4,22-dien-3-one (4) were synthesized by a similar method. The cytotoxicity of the synthesized compounds against sk-Hep-1 (human liver carcinoma cell line), H-292 (human lung carcinoma cell line), PC-3 (human prostate carcinoma cell line) and Hey-1B (human ovarian carcinoma cell line) cells were investigated. The presence of a cholesterol-type side chain appears to be necessary for the biological activity.
Cui
Jianguo
J
Department of Chemistry, Guangxi Teachers Education University, Nanning, PR China. cuijg1954@126.com
Huang
Liliang
L
Fan
Lei
L
Zhou
Aimin
A
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D002774:Cholestadienes / Q000138:chemical synthesis* / Q000633:toxicity; D002783:Cholestenones / Q000138:chemical synthesis* / Q000633:toxicity; D006801:Humans; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry; D011161:Porifera / Q000737:chemistry* / Q000145:classification; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry
C528943:6-hydroximino-24-ethylcholest-4,22-dien-3-one; C528941:6-hydroximino-24-ethylcholest-4-en-3-one; C528942:6-hydroximinocholest-4-en-3-one; D000970:Antineoplastic Agents; D002774:Cholestadienes; D002783:Cholestenones; D010091:Oximes; D013256:Steroids