The Cephalostatins. 23. Conversion of Hecogenin to a Steroidal 1,6-Dioxaspiro[5.5]nonane Analogue for Cephalostatin 11.

Abstract

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.

• Authors: George R Pettit, Bryan R Moser, Delbert L Herald, John C Knight, Jean-Charles Chapuis, Xing Zheng
• Journal: Journal of natural products (J Nat Prod) Vol. 78 Issue 5 Pg. 1067-72 (May 22 2015) ISSN: 1520-6025 [Electronic] United States
• PMID: 25915559 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Alkanes
• Antineoplastic Agents
• Furans
• Phenazines
• Pyrazines
• Sapogenins
• Spiro Compounds
• Steroids
• spiroketal
• cephalostatin I
• cephalostatin 11
• hecogenin
• hecogenin acetate
• nonane

Topics

• Alkaloids (chemistry, metabolism)
• Alkanes (chemistry)
• Animals
• Antineoplastic Agents (chemistry, metabolism)
• Furans (chemistry)
• Humans
• Molecular Structure
• Phenazines (chemistry, metabolism)
• Pyrazines (chemistry)
• Sapogenins (chemistry, metabolism)
• Spiro Compounds (chemistry, metabolism)
• Steroids (chemistry, metabolism)