This project is the synthetic organic chemistry component of this program project. Our tasks is the synthesis of research quantities of lead compounds. These compounds are supplied from other projects for biological testing. Amounts ranging from 100 mg to 1 g are sufficient for confirmation of initial in vitro activity and testing in secondary systems, such as mouse mammary organ culture (MMOC). If the results are promising, short-term animal testing can also be performed with these quantities of test materials, as can mechanistic evaluations. In this context, this project is also responsible for derivatization and synthetic modification of lead compounds for structure-activity relationships (SARs), which will be used for lead optimization. In addition, project 5 will perform scale-up syntheses of lead compounds for use in full-term animal studies for the assessment of chemopreventive activity. Scale-up synthesis will involve multi-step processes and possibly stereoselective transformations for quantities ranging from 500 g to 2 kg. The goal of project 5 is the efficient and timely synthesis of compounds from the discovery part of the program to the stage of complete biological evaluation. To accomplish this goal, a flexible, competent, and responsive synthetic group has been assembled. In ongoing studies, this project will focus on large scale syntheses of sulforamate, oxomate, sulforaphane, brassinin, cyclobrassinin, 4'-bromoflavone, E-resveratrol and 4'-bromorot- 2'-enonic acid for inclusion in animal carcinogenesis models (project 3). We will also continue analog syntheses of resveratrol, rotenoids and isoflavones. Thus, in a highly coordinated manner, project 5 will contribute to the further development of lead compounds that have or will emerge from this program project.
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