Herbicidin A

Some of nucleoside antibiotics include complex structures as well as sensitive functionality, which are challenging targets for organic chemists. Among complex nucleoside antibiotics, there are also good drug candidates because they possess a variety of interesting biological properties. Herbicidin B and fully protected tunicaminyluracil, which were undecose nucleoside antibiotics, were synthesized using a samarium diiodide (SmI(2)) mediated aldol reaction with the use of alpha-phenylthioketones as enolate sources. The characteristics of the SmI(2)-mediated aldol reaction are that the enolate can be regioselectively generated and the aldol reaction proceeds under near neutral condition. This reaction is proved to be a powerful reaction for the synthesis of complex nucleoside antibiotics. The synthesis of caprazol, the core structure of caprazamycins, was conducted by the strategy including beta-selective ribosylation without using a neighboring group participation and the construction of a diazepanone by a modified reductive amination. Our synthetic route would provide a range of key analogues with partial structures to define the pharmacophore, which can be a lead for the development of more effective anti-bacterial agents.

Herbicidin A is a potent herbicide against dicotyledonous plants as well as an antibiotic against phytopathogens. In this study, fermentation parameters for herbicidin A production in submerged culture ofStreptomyces scopuliridisM40 were investigated. The herbicidin A concentration varied with the C/N ratio. High C/N ratios (>4) resulted in a herbicidin A production of more than 900 mg/l, whereas maximally 600 mg/l was obtained at ratios between 1 and 3.5. In 5-L batch fermentation, there was a positive correlation between the oxygen uptake rate (OUR) and herbicidin A production. Once the OUR increased, the substrate consumption rate increased, leading to an increase in volumetric productivity. Mechanical shear force affected the hyphal morphology and OUR. When the medium value of hyphal size ranged from 150 to 180 μm, high volumetric production of herbicidin A was obtained with OUR values >137 mg O2/l·h. The highest herbicidin A concentration of 956.6 mg/l was obtained at 500 rpm, and coincided with the highest relative abundance of hyphae of 100-200 μm length and the highest OUR during cultivation. Based on a constant impeller tip speed, which affects hyphal morphology, herbicidin A production was successfully scaled up from a 5-L jar to a 500-L pilot vessel.

The undecose nucleoside antibiotics herbicidin C and aureonuclemycin are biologically highly active and represent challenging targets for total synthesis. Herein, the gradual evolution of our synthetic strategy toward these natural products is described in detail. The initial route encompasses metalate addition chemistry but suffers from poor stereochemical control. In contrast, the ultimately successful strategy benefits from a variety of reagent-controlled stereoselective transformations, including a surprisingly facile and highly diastereoselective N-glycosylation process. The presented work also describes new building blocks that might find further application in carbohydrate chemistry.