Direct isolation

Tetracyclines are produced by various Streptomyces strains and are extensively applied in human and veterinary medicine. They display a broad spectrum of antimicrobial activity in combination with low toxicity and can be applied orally. The most commonly prescribed tetracycline drugs are tetracycline itself and oxytetracycline, an oxygenated derivative, which are directly isolated from fermentation liquors, and doxycycline whose partial synthesis from oxy-... 

There are three general processes that ate used, as of ca 1996, woddwide for steroid production (/) direct isolation from natural sources, (2) partial synthesis from steroid raw materials that have been isolated from plants and animals, and (J) total synthesis from nonsteroidal starting materials (120). 

The direct isolation of the well defined and stable neopentyl glycol arylboronic esters, without the need for an intermediate aqueous work-up. 

A general scheme for the bloassay directed Isolation and characterization of antimicrobial agents from plants Is presented and discussed. The utility of the procedure Is demonstrated by the characterization of two antimicrobial alkaloids from the tulip tree, Llrlodendron tullplfera L. The generalization of the approach to the study of allelopathic agents In plants Is suggested. 

In the course of the tempestuous development of organophosphorus chemistry, interest has only recently been focused on compounds of formally quinquevalent phosphorus having coordination number 3, such as 1, 2, or 3, although one of the other species of this kind has long been postulated as reactive intermediate of solvolysis of phosphorylation reactions. Definite evidence of even proof of the existence of such coordinatively unsaturated phosphorus compounds, however, has been obtained only recently in mechanistic studies, by trapping reactions with suitable cycloaddends, or actually by direct isolation. 

In this presentation, bioactivity-directed isolation and stmcture elucidation of the active constituents will be given. Structures of the constituents, which form namely terpenoids (sesqni, di- and triterpenoids) were based on spectroscopic tech-niqnes, particnlarly intensive NMR and Mass spectroscopies. 

Direct isolation of sufficient quantities of each metabolite for structural characterization, assay validation and pharmacological or toxicological testing from in vivo studies using biological specimens is, therefore, often impossible, particularly from dmgs with a low therapeutic index. Furthermore, many metabolites have structural modifications which are difficult to replicate by traditional chemical methods. A number of synthetic steps may be required to prepare such metabolites from the API, or, in the worst case, a completely new synthetic route may need to be developed. 

Treatment of 2-amino-l,3,4-oxadiazoles 13 with bromoketones in boiling ethanol gives imidazo[2,l-h][l,3,4]oxadiazoles 20 directly (isolated as salts (82JIC1170).2... 

Bioassay-directed isolation of antifungal compounds from the bark of Macaranga monandrayie ( eA. two clerodane-type diterpenes, kolavenic acid and 2-oxo-kolavenic acid, with moderate activity against Phomopsis viticola... 

Direct isolation ( one-pot ) processes should be considered for materials prepared for Phase 2 and later development. Examples of this were shown in Schemes 2.3 and 2.4 for the tosylate salt 13 and the product 15 from the Dimroth rearrangement. Considerable processing time may be saved, resulting in lower COG from reduced labor costs. The attendant savings on solvent costs and waste disposal can also reduce COG. Some research time may be necessary to develop these processes, in particular fine-tuning the processes to purge impurities. In early phases of dmg development the fastest scale-up may be through conventional extractive work-up, concentration, and crystallization. 

Allylic hydroperoxides are primary products in the autoxidation of - olefins, and lack of definite information on their reactivity and chemical behavior has hampered efforts to understand olefin oxidation mechanisms (2). This deficiency is most strongly felt in determining the relative rates of addition and abstraction mechanisms for acyclic olefins since assignment of secondary reaction products to the correct primary source is required. Whereas generalizations about the effect of structure on the course of hydroperoxide decompositions are helpful, most questions can be answered better by directly isolating the hydroperoxides involved and observing the products formed by decomposition of the pure compounds. 

Thus, it is apparent that the initial a-hydroxylation of nitrosamine constitutes a possibly important pathway to produce the so-called proximate carcinogen. The a-hydroxylated nitrosamines have eluded direct isolation, although derivatives such as esters and ethers have been prepared by various groups (4, 5, 6, 7, 8). These materials, particularly g-acetoxydimethylnitrosamine (9), have been shown to be very potent carcinogens. 

Engel, W., Bahr, W., Schieberle, P. (1999) Solvent assisted flavour evaporation—a new and versatile technique for the careful and direct isolation of aroma compounds from complex food matrices. Eur. Food Res. Technof 209 237-241. 

Bioassay directed isolation of serine protease inhibitors from Coscinoderma mathewsi yielded the 1-methylherbipoline salts (366-367) of known sesterterpenes halisulfate-1 (359) and suvanine (358) [321]. Coscinosulfate 1 (368), a sesquiterpene sulfate, was isolated from a New Caledonian collection of C. mathewsi. It displayed significant activity as an inhibitor of the protein phosphatase Cdc25 [322]. A total synthesis starting from (+)-sclareolide was described [323]. 

Direct isolation of human central nervous system stem cells. Uchida, N., Buck,... 

This chapter will focus on various classes of compounds that possess potent antitumor, anti-HIV, and antifungal activity recently discovered in my laboratory. These compounds were obtained by bioactivity- and mechanism of action-directed isolation and characterization... 

Identification of Alcohols. The alcohol component of the plasticizers, after direct isolation, can be identified by gas chromatography, whereas, paper or thin layer chromatographic methods require that alcohols be converted into suitable derivatives prior to identification. 

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