The Cephalostatins. 23. Conversion of Hecogenin to a Steroidal 1,6-Dioxaspiro[5.5]nonane Analogue for Cephalostatin 11.
Cephalostatin 1 (1) has proved to be a remarkably potent cancer cell growth inhibitor. Since this steroidal alkaloid constituent of the marine worm Cephalodiscus gilchristi possesses a complex structure, providing preclinical supplies by total synthesis continues to be challenging. Therefore, syntheses of less complex structural modifications of this important pyrazine have also received substantial attention. Herein are summarized the synthesis of [5.5]spiroketal 5, a simplified right-side steroidal unit of 1, in seven steps from hecogenin acetate (11) with an overall yield of 4.6%. Consistent with other SAR studies, such reduction in structural complexity compared to 1 led to loss of cancer cell growth inhibitory activity against the P388 lymphocytic leukemia cell line.
Department of Chemistry and Biochemistry, Arizona State University, P.O. Box 871604, Tempe, Arizona 85287-1604, United States.
George R
GR
Pettit
Department of Chemistry and Biochemistry, Arizona State University, P.O. Box 871604, Tempe, Arizona 85287-1604, United States.
Bryan R
BR
Moser
Department of Chemistry and Biochemistry, Arizona State University, P.O. Box 871604, Tempe, Arizona 85287-1604, United States.
Delbert L
DL
Herald
Department of Chemistry and Biochemistry, Arizona State University, P.O. Box 871604, Tempe, Arizona 85287-1604, United States.
John C
JC
Knight
Department of Chemistry and Biochemistry, Arizona State University, P.O. Box 871604, Tempe, Arizona 85287-1604, United States.
Jean-Charles
JC
Chapuis
Department of Chemistry and Biochemistry, Arizona State University, P.O. Box 871604, Tempe, Arizona 85287-1604, United States.
Xing
X
Zheng
D000470:Alkaloids / Q000737:chemistry / Q000378:metabolism; D000473:Alkanes / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D005663:Furans / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D010619:Phenazines / Q000737:chemistry* / Q000378:metabolism*; D011719:Pyrazines / Q000737:chemistry; D012502:Sapogenins / Q000737:chemistry / Q000378:metabolism*; D013141:Spiro Compounds / Q000737:chemistry* / Q000378:metabolism*; D013256:Steroids / Q000737:chemistry* / Q000378:metabolism*
D000470:Alkaloids; D000473:Alkanes; D000970:Antineoplastic Agents; D005663:Furans; D010619:Phenazines; D011719:Pyrazines; D012502:Sapogenins; D013141:Spiro Compounds; D013256:Steroids; C520774:spiroketal; C454806:cephalostatin I; C086773:cephalostatin 11; C007908:hecogenin; C505698:hecogenin acetate; C017573:nonane