Assembly of Multicyclic Isoquinoline Scaffolds from Pyridines: Formal Total Synthesis of Fredericamycin A

The construction of isoquinoline skeleton typically starts with benzene derivatives as substrates with the assistance of acids or transition metals. Disclosed here is a concise approach to prepare isoquinoline analogues...

Novel Fredericamycin Variant Overproduced by a Streptomycin-Resistant Streptomyces albus subsp. chlorinus Strain

Streptomycetes are an important source of natural products potentially applicable in the pharmaceutical industry. Many of these drugs are secondary metabolites whose biosynthetic genes are very often poorly expressed under laboratory cultivation conditions. In many cases, antibiotic-resistant mutants exhibit increased production of natural drugs, which facilitates the identification and isolation of new substances. In this study, we report the induction of a type II polyketide synthase gene cluster in the marine strain Streptomyces albus subsp. chlorinus through the selection of streptomycin-resistant mutants, resulting in overproduction of the novel compound fredericamycin C2 (1). Fredericamycin C2 (1) is structurally related to the potent antitumor drug lead fredericamycin A.

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

This is a review of our efforts toward the synthesis of a group of natural products that display noteworthy biological activity: Fredericamycin A, nothapodytine B, and topopyrones B and D. In each case, directed aromatic functionalization methodology greatly facilitated the assembly of the key molecular subunits.