Kober reaction

Kober reaction of phenolic steroids with strong adds leading to polymethyne dyes [18, 19]. 

Marlow HW. Groups involved in the Zimmermann and Kober reactions. J Biol Chem 1950 183 167-71. 

The best method for urinary estrogens of clinical importance is that devised by Brown (B20, B21). This depends on the modification of the Kober-Ittrich color reaction to provide an extremely sensitive fluorescence reaction (see also S2). Acid hydrolysis (15 minutes) is followed by either extraction (2X1 volume) evaporation to dryness a partition between petroleum ether-benzene and water (estriol) and 1.6% NaOH (estradiol, estrone). The two solutions are methylated (10 minutes) and extracted with ether the ether is evaporated, and the residues are run on alumina columns. In the original procedure the less specific and sensitive form of the Kober reaction required more extensive purification one technician could complete four estimations in 1.5-2 days. The new procedure enables four determinations to be made every 5-6 hours. An ultrarapid version of this method for specialized obstetric use has been devised by Gemzell and his group and will be published shortly. By this method, twelve samples can be measured in 3 hours by one technician. 

For the assay of estriol, estrone, and estradiol in umbilical cord blood (A3, D8, II, M3, R17) and in infant urine (DIO) methods designed for adult material have been used, and there appears to be no reason to doubt the validity of the results obtained. In all cases the methods depended upon column chromatography for separation, with various modifications of the Kober reaction or fluorimetry, for assay. 

A few analytical methods have been selected as being of particular interest to organic chemists. The spectrophotometric determination of oxo-steroids as their glyoxalyl derivatives is mentioned on p. 331. The Kober reaction and its modifications,in which a phenolic steroid is heated with moderately concentrated sulphuric acid to generate chromogenic materials, is still not fully understood. Oestradiol 3-methyl ether, with 78 % sulphuric acid, gives a mixture including isomers of the 17-methyl-18-nor structure (776), and the derivative (777) with an... 

Jung and co-workers [95] have quoted a shortened procedure with only a single TLC stage on silica gel, using benzene-ether (40 + 60) and Kober-reaction on the eluates. 

One of the oestrogens secreted by the ovary. For a more detailed account of its role, see menstrual cycle. It is metabolized to oestriol and excreted in the urine. Specific oestradiol measurements in plasma and urine can be made by gas chromatography or by radioimmunoassay. It can also be determined, along with other oestrogens, by the Kober reaction. Decreased levels of oestradiol are found in pituitary or ovarian malfunction while increased levels can occur in some ovarian tumours. 

Kober R, Papadopoulos K, Miltz W, Enders D, Steglich W, Reuter H, Puff H (1985) Synthesis of diastereo- and enantiomerically pure a-amino-y-oxo acid esters by reaction of acyliminoacetates with enamines derived from 6-membered ketones. Tetrahedron 41 1693... 

In an attempt to identify the chromophoric systems resulting from reactions of steroids with strong acids ( colour reactions Kober, Allen, Oertel, Talbot, Salkowski, and Liebermann-Burchard reactions) a detailed study has been made, with use of all the usual spectroscopic techniques. Visible colours are attributed generally to charge-transfer between the steroid, as donor, and a delocalized carbonium ion, generated from the steroid in acidic media, acting as acceptor. The structures of the steroidal carbonium ions are discussed. 

The cyclization a /S-amino acid was first carried out by Stau-dinger. Klever, and Kober to provide an alternative synthetic route for the proof of structure trf l-boozyl-3 diniethyl-4-pliefiyl 2-azetidinone (L.XXII), which had been obtained by a cyoloaddition reaction [section The amino a d (LXXll was oyclized in 60%... 

Kober, R., and Steglich, W., Reaction of acylaminobromomalonates and acylaminobromoacetates with trialkylphosphites. A simple synthesis of ethyl 2-amino-2-(diethoxyphosphoryl)acetate, Liebigs Ann. Chem., 599, 1983. 

B21. Brown, J. B., MacNaughtan, C., Smith, M. A., and Smyth, B., Further observations on the Kober colour and Ittrieh fluorescence reactions in the measurement of oestriol, oestrone, and oestradiol. J. Endocrinol. 40, 175-188 (1968). 

Kober BJ, Scheule AM, Voth V, Deschner N, Schmid E, Ziemer G. Anaphylactic reaction after systemic application of aprotinin triggered by aprotinin-containing fibrin sealant. Anesth Analg 2008 107(2) 406-9. 

A reaction in which oestrogens (Kober chromogens), when heated with sulphuric acid, yield an orange-yellow complex which can be estimated fluorimetrically or colorimetrically. 

The non-ketonic oestrogens are more important pharmaceutically the parent materials are usually not assayed as such, but are controlled by measurement of physical characteristics such as optical rotation or ultraviolet absorption (see Table 29). Where they appear in formulations (frequently as oily injections) the reaction most commonly employed for their determination is that due to Kober in which a magenta colour is formed by reaction of the oestrogen with phenolsulphonic acid and sulphuric acid the colour produced has an absorption maximum at about 525 m/Uy but other oestrogens also react to give a brownish colour with absorption maximum at 420 m. The method is further complicated by the fact that... 

Kober E, Schroeder H, Ratz R, Ulrich H, Grundmann C (1962) Synthesis of polyfluorinated heterocycles by indirect fluorination with silver fluorides. I. Fluoro-s-triazines and reactions of cyanuric fluoride. J Org Chem 27 2577-2580... 

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