Furaquinocin B

A modular approach to the total synthesis of furaquinocins culminated in the total syntheses of furaquinocin A, B, and E. A Pd-catalyzed dynamic kinetic asymmetric transformation (DYKAT) on carbonates derived from Baylis-Hillman adducts, followed by a reductive Heck cyclization allows the enantio- and diastereoselective construction of dihydrobenzofuran 32. Introduction of a double unsatured side chain via Horner-Wadsworth-Emmons reaction and assembly of the naphthoquinone with squaric acid based methodology leads to furaquinocin E. The use of differentially substituted squaric acid derivatives allows the synthesis of three analogues of furaquinocin E. The additional stereocenters in furaquinocin A and B can be introduced with a diastereoselective Sakurai allylation. The stereoselective elongation of the side chain is possible using cross metathesis or ring closing metathesis. The obtained late-stage intermediates were successfully transformed to furaquinocin A and B.

Two novel antibiotics, furaquinocins A and B were isolated from the culture broth of Streptomyces sp. KO-3988. These antibiotics possess cytocidal activities against HeLa S3 cells in vitro at concentrations of 3.1 micrograms/ml for A and 1.6 micrograms/ml for B. Neither substance possessed antimicrobial activities against Gram-positive and Gram-negative bacteria, fungi or yeast at a concentration of 1,000 micrograms/ml.

Actinomycetes are the most prominent group of microorganisms that produce biologically active compounds. Among them, special attention is focused on bacteria in the genus Streptomyces. Streptomycetes are an important source of biologically active natural compounds that could be considered therapeutic agents. In this study, we described the identification, purification, and structure elucidation of two new naphthoquinone-based meroterpenoids, furaquinocins K and L, from Streptomyces sp. Je 1-369 strain, which was isolated from the rhizosphere soil of Juniperus excelsa (Bieb.). The main difference between furaquinocins K and L and the described furaquinocins was a modification in the polyketide naphthoquinone skeleton. In addition, the structure of furaquinocin L contained an acetylhydrazone fragment, which is quite rare for natural compounds. We also identified a furaquinocin biosynthetic gene cluster in the Je 1-369 strain, which showed similarity (60%) with the furaquinocin B biosynthetic gene cluster from Streptomyces sp. KO-3988. Furaquinocin L showed activity against Gram-positive bacteria without cytotoxic effects.