CP-225,917 and CP-263,114, novel Ras farnesylation inhibitors from an unidentified fungus. I. Taxonomy, fermentation, isolation, and biochemical properties.
نویسندگان
چکیده
During the course of our screening for squalene synthase inhibitors and Ras farnesylation inhibitors, a novel fungal culture was discovered to produce two structurally unique compounds, CP-225,917 and CP-263,114, as well as zaragozic acid A (squalestatin I). The two compounds are characterized by a bicyclo[4.3.1]dec-1,6-diene core plus two extended alkyl chains. CP-225,917 and CP-263,114 inhibit Ras farnesyl transferase from rat brain with IC50 values of 6 microM and 20 microM, respectively. CP-225,917 inhibits squalene synthase with an IC50 value of 43 microM and CP-263,114 with an IC50 of 160 microM. The producing organism, though not fully classified, exhibits the characteristics of a sterile Phoma species.
منابع مشابه
Total synthesis of the CP-molecules (CP-263,114 and CP-225,917, phomoidrides B and A). 3. Completion and synthesis of advanced analogues.
The completion of the total syntheses of the CP-molecules is reported. Several strategies and tactics, including the use of amide-based protecting groups for the homologated C-29 carboxylic acid and the use of an internal pyran protecting group scheme, are discussed. The endeavors leading to the design of new methods for the homologation of hindered aldehydes and to the isolation of a polycycli...
متن کاملTotal synthesis of the CP-molecules (CP-263,114 and CP-225,917, phomoidrides B and A). 1. Racemic and asymmetric synthesis of bicyclo[4.3.1] key building blocks.
A brief introduction into the chemistry of the CP-molecules is followed by first-generation synthetic sequences toward key building blocks for their total synthesis. Processes for both racemic and enantiomerically enriched bicyclo[4.3.1] ketone 6 or its equivalent are described, and the absolute stereochemistries of the optically enriched intermediates are determined. The efficient route develo...
متن کاملFR901469, a novel antifungal antibiotic from an unidentified fungus No.11243. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological properties.
FR901469 is a novel antifungal antibiotic produced by an unidentified fungus No.11243. This compound was isolated from the culture broth by solvent extraction, HP-20 and YMC ODS gel column chromatography, and lyophilization. FR901469 is a white powder which melts at 182 approximately 187 degrees C and possesses the molecular formula C71H116N14O23. This compound has good water solubility. FR9014...
متن کاملTotal synthesis of the CP-molecules (CP-263,114 and CP-225,917, phomoidrides B and A). 2. Model studies for the construction of key structural elements and first-generation strategy.
Crucial model synthetic and mechanistic studies directed toward the development of methodology for the construction of the maleic anhydride moiety of the CP-molecules are described. Studies directed toward the stereoselective attachment of the upper side chain, culminating in the discovery of long-range stereochemical control, are also discussed. In addition, a first-generation strategy toward ...
متن کاملNovel polyether antibiotics X-14868A, B, C, and D produced by a Nocardia. Discovery, fermentation, biological as well as ionophore properties and taxonomy of the producing culture.
Polyether antibiotics are a large class of microbial secondary metabolites generally produced by soil actinomycetes of the genus Streptomyces'). Intensive search for new polyether antibiotics has in recent years revealed that other genera of streptomycetes also produce these antibiotics. Laidlomycin is produced by Streptoverticillum eurocidium'). Cationomycin'), antibiotics CP-47,433 and CP-47,...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of antibiotics
دوره 50 1 شماره
صفحات -
تاریخ انتشار 1997