Dictyostatin and its analogs show great promise as new anticancer agents.
The present invention provides dictyostatin analogs, synthetic
intermediates for the synthesis of dictyostatin analogs, and synthetic
methods for the synthesis of such analogs and intermediates. Dictyostatin
analogs can have the following structure or its enantiomer wherein
R.sup.1 is H, an alkyl group, an aryl group, an alkenyl group, an alkynyl
group, or a halogen atom; R.sup.2 is H, a protecting group, an alkyl
group, a benzyl group, a trityl group, --SiR.sup.aR.sup.bR.sup.c,
CH.sub.2OR.sup.d, or COR.sup.e; R.sup.a, R.sup.b and R.sup.c are
independently an alkyl group or an aryl group; R.sup.d is an alkyl group,
an aryl group, an alkoxylalkyl group, --R.sup.iSiR.sup.aR.sup.bR.sup.c or
a benzyl group, wherein R.sup.i is an alkylene group; R.sup.e is an alkyl
group, an allyl group, a benzyl group, an aryl group, an alkoxy group, or
--NR.sup.gR.sup.h, wherein R.sup.g and R.sup.h are independently H, an
alkyl group or an aryl group; R.sup.3 is (CH.sub.2).sub.n where n is and
integer in the range of 0 to 5, --CH.sub.2CH(CH.sub.3)--, --CH.dbd.CH--,
--CH.dbd.C(CH.sub.3)--, or --C.ident.C--; R.sup.4 is wherein R.sup.23a
is H, a protecting group, an alkyl group, a benzyl group, a trityl group,
--SiR.sup.aR.sup.bR.sup.c, CH.sub.2OR.sup.d, or COR.sup.e; R.sup.23b is
H, a protecting group, an alkyl group, a benzyl group, a trityl group,
--SiR.sup.aR.sup.bR.sup.c, CH.sub.2OR.sup.d, or COR.sup.e, or R.sup.23a
and R.sup.23b together form a portion of six-membered acetal ring
incorporating CR.sup.tR.sup.u; R.sup.t and R.sup.u are independently H,
an alkyl group, an aryl group or an alkoxyaryl group; and R.sup.5 is H or
OR.sup.2b, wherein R.sup.2b is H, a protecting group, an alkyl group, an
aryl group, a benzyl group, a trityl group, --SiR.sup.aR.sup.bR.sup.c,
CH.sub.2OR.sup.d, or COR.sup.e; provided that the compound is not
dictyostatin 1.