Compounds useful in the synthesis of halichondrin B analogs

摘要

In general, the invention features compounds useful for the synthesis of analogs of halichondrin B, such as eribulin or pharmaceutically acceptable salts thereof, e.g., eribulin mesylate. Exemplary compounds are of formula (I), (II), or (III):;

主权项

1. A compound having the formula:wherein X is halogen or oxo; Q is —C(O)H, —CH═CHC(O)OY1, —C(R)H(CH2)nOY1, or —C(R)HCH2C(O)OY1; R is H or —OY2; n is 1 or 2; Y1, Y2, Y3, and Y4 are each independently H or a hydroxyl protecting group; T is oxo or —OY5; and Y5 is H or a hydroxyl protecting group, or Y5, together with the oxygen atom to which it is bound, is a leaving group, wherein each of Y3 and Y4 is, independently and together with the oxygen atom to which it is bound, an ester, carbonate, carbamate, sulfonate, or ether hydroxyl protecting group; Y3 and Y4 together with the oxygen atoms to which they are bound are a cyclic carbonate, cyclic boronate, or cyclic silylene hydroxyl protecting group, or Y3 and Y4 together are acetal, ketal, or 1,1,3,3-tetraisopropylsiloxanediyl.