The quest for novel antitumor agents for treatment of breast disease centers on the development of transition state (multisubstrate) analogs of steroid sulfurylation. However, the scope of the work includes an evaluation of each component of the multisubstrate analog as well. Accordingly, a general method was developed for synthesis of substituted estrone 3-phosphates, which leads to 4-nitoestrone 3-phosphate in acceptable yield. The synthesis of 3P1-estrone 5'P2-(3'-phosphoadenosine)5'-pyrophosphate has been repeated and the identity of the product has been confirmed. Moreover, the Ki is in agreement with that obtained in an earlier study. The importance of the 3'phosphate ether in this multisubstrate analog is demonstrated. 4-Nitroestrone 3-methyl ether, synthesized on a scale appropriate for study on DMBA induced mammary tmors, demonstrates in preliminary study, a significant effect.