Synthesis of Optically Active and Biologically Active Compounds

Based on the consideration that biologically active chiral compounds should be prepared in optically active forms showing desired biological activities, the compounds not only exhibiting interesting biological activities but also bearing intriguing structures were selected as synthetic targets and their efficient syntheses were studied by employing optical resolution, asymmetric synthesis, and chemical transformation. Thus, efficient syntheses of anticancer agents such as anthracyclines, nogalamycins, and sesbanimides were accomplished in optically active forms. Syntheses of optically active quinocarcin and fredericamycin A showing pronounced anticancer activities were also studied. A number of efficient synthetic routes to the optically active key intermediates of carbapenem antibiotics and antihypertensive peptide-like renin inhibitors were successfully explored. 1. Introduction 2. Synthetic Studies on Optically Active Anthracyclines 2.1. Synthesis of 4-Demethoxyanthracyclinones 2.2. Synthesis of an L-Daunosamine Derivative 2.3. Synthesis of 4-Demethoxyanthracyclines 2.4. Synthesis of Anthracycline Congeners 3. Synthetic Studies on Optically Active Nogalamycin Congeners 3.1. Synthesis of the CDEF-Ring 3.2. Synthesis of Nogalamycin Congeners 3.3. Structure-Activity Relationships of Nogalamycin Congeners 4. Synthetic Studies on Optically Active Sesbanimides 4.1. Synthesis of Sesbanimide A and B 4.2. Synthesis and Structure-Activity Relationships of Sesbanimide Congeners 5. Synthetic Studies on Optically Active Quinocarcin 6. Synthetic Studies on Optically Active Fredericamycin A 7. Synthetic Studies on Optically Active Carbapenem Key Intermediates 7.1. Synthesis by the Cycloaddition Reaction of a Nitrone 7.2. Synthesis by the [2 + 2] Cycloaddition Reactions 7.3. Synthesis by the Reformatsky Reaction 8. Synthetic Studies on the Key Intermediates of Peptide-Like Renin Inhibitors 8.1. Synthesis by the 1,2-Addition Reactions with Aldehydes 8.2. Synthesis by the 1,2-Addition Reaction with an Imine 8.3. Synthesis by the [2 + 2] Cycloaddition Reaction 8.4. Synthesis Employing Optical Resolution, Asymmetric Reduction, and Chemoselective Amidation 9. Conclusion