Our efforts toward the drug development of new potent antitumor anthracycline antibiotic Aclacinomycin A have been extended to the studies on biogenesis, structure-activity relationships and microbial and chemical transformations to produce more active and less toxic compounds than adriamycin. Since 1973 we have produced about 100 compounds : aclacinomycins, 2-hydroxyaclacinomycins, 13-methylaclacinomycins, 4-Ο- methylaclacinomycins, 11- hydroxyaclacinomycins, 4''' -dehydrorhodomycin Y, 11 -hydroxycinerubin A, rhodirubins, roseorubicins, baumycins, 4 - hydroxybaumycinols, feudomycins, 1 -hydroxydaunorubicinol, trisarubicinol, 4''' aminoaclacinomycin derivatives, cinerulosyl-2 - deoxyfucosylrhodosaminyldaunomycinone derivatives by fermentation, by microbial glycosidation and by chemical modification. The biosynthetic pathways that transform the hypothetical decaketide precursors of anthracyclinones to the appropriate end products were elucidated on the basis of the chemical structures of anthracyclines newly produced by feeding presumptive biosynthetic intermediates to mutants blocked in the biosynthesis of parent metabolites. Outline of fermentation and purification, structures of anthracycline antibiotics produced by microorgnisms, biosynthesis of anthracyclinones, biological activity and its relationships to chemical structure were reviewed.
Chemical synthesis of anthracycline antibiotics which attract much attention due to their promising therapeutic properties against various types of human cancers, is reviewed. The synthetic routes to these novel antibiotics are described on a) preparation of the aglycones, anthracyclinones, b) synthesis of the aminosugars represented by L-daunosamine, and c) coupling of the two components by glycosidation reaction. The aglycone syntheses on which much synthetic efforts have recently been paid, are further summarized based on the key reactions constructing the tetracyclic system of anthracyclinones : a) Friedel-Crafts reaction, b) Diels-Alder reaction, and c) 1, 2- or 1, 4-addition reaction; and on the preparation methods for optically active aglycones. Full scope of the anthracycline synthesis is disclosed by delineating the key point of each synthetic scheme.
Present review describes recent investigations on the intermediates in the biosynthesis of cyclic tetrapyrroles such as heme, chlorophyll, and vitamin B12. Hydroxymethylbilane has been newly found to be the product of the reaction with PBG deaminase and to be the substrate of uroporphyrinogen III cosynthetase. Porphyrinogen carboxy-lyase has been proved to remove carbon dioxide from the four acetate chain of uroporphyrinogen III in stereochemically same manner. The new route to cobyrinic acid, a precursor of vitamin B12' from uroporphyrinogen III is established by synthesis of radioactive pyrroles. It has been demonstrated that methylation by methionine occurrs at C-2 position, first, and succesive ring contraction to corrin macrocycle of vitamin B12 liberates acetic acid arising from C-20 atom and C-20 methyl moiety.
This article describes the syntheses of various types of novel condensation polymers by vinylogous nucleophilic substitution polymerization and related aromatic nucleophilic substitution polymerization. After a brief introduction of the chemistry of vinylogous nucleophilic substitution, the polymerizations of open-chain and ring-containing activated vinyl monomers, as well as activated aromatic monomers, with various nucleophiles such as diamines, bisphenols, and dithiols are presented.