Interphylal product splicing:: The first total syntheses of cephalostatin 1, the north hemisphere of ritterazine G, and the highly active hybrid analogue, ritterostatin GN1N

被引:118
作者
LaCour, TG [1 ]
Guo, CX
Bhandaru, S
Boyd, MR
Fuchs, PL
机构
[1] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA
[2] NCI, Lab Drug Discovery Res & Dev, Frederick, MD 21702 USA
关键词
D O I
10.1021/ja972160p
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Convergent total syntheses of the extremely potent cell growth inhibitor cephalostatin 1 and two hybrid analogues, ritterostatins G(N)1(N) and G(N)1(S), have been achieved. Ritterostatin G(N)1(N) displays sub-nanomolar activity in the 60 cell line human tumor panel of the National Cancer Institute. The North hemisphere of ritterazine G was efficiently constructed from hecogenin acetate in 15% yield over 13 steps. Extension of a key photolysis/Prins sequence to intermediates 19 and 32 proceeded in excellent yield, leading to installation of the Delta(14) moiety in the-North G-and South I steroidal subunits. Application of a method for directed unsymmetrical coupling furnished the natural and analogue pyrazines in good yield from the cephalostatin and ritterazine components.
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页码:692 / 707
页数:16
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