INTERPHYLAL PRODUCT SPLICING - THE FIRST TOTAL SYNTHESES OF CEPHALOSTATIN-1, THE NORTH HEMISPHERE OF RITTERAZINE-G, AND THE HIGHLY-ACTIVE HYBRID ANALOG, RITTEROSTATIN G(N)1(N)

Convergent total syntheses of the extremely potent cell growth inhibit or cephalostatin 1 and two hybrid analogues, ritterostatins G(N)1(N) a nd G(N)1(S), have been achieved. Ritterostatin G(N)1(N) displays sub-n anomolar activity in the 60 cell line human tumor panel of the Nationa l Cancer Institute. The North hemisphere of ritterazine G was efficien tly constructed from hecogenin acetate in 15% yield over 13 steps. Ext ension of a key photolysis/Prins sequence to intermediates 19 and 32 p roceeded 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 ritterazin e components.