Winterstein acid

The absolute configuration of the terpenoid core of taxine I was deduced by the X-ray analysis of the bromoderivative of a transformation product of its corresponding cinnamate (taxinine) [60], The L (1() absolute configuration of the dextrorotatory Winterstein acid obtained from the degradation of crude taxine was established by comparison with the rotatory power of the semisynthetic enantiomers prepared from D- and L P-phenyl-p-alanine [61]. 

Schulze and Winterstein, in 1899, proved that aiginine was S-guani-dine-a-aminovalerianic acid by s)mthesis from cyanamide and ornithine —... 

The mammalian alkaloids are formed from aromatic amino acids and their metabolically derived amines by reaction with carbonyl substrates at physiological pH. The reaction is catalyzed by acid and is commonly referred to as the Pictet-Spengler cyclization (I0a,b,II). Winterstein and Trier in 1910 proposed that the Pictet-Spengler reaction might be of significance in the biosynthesis of benzylisoquinoline alkaloids in plants (5a). The carbonyl compounds participating in the Pictet-Spengler synthesis of mammalian alkaloids are aldehydes and a-keto acids, which are produced... 

Astrup and Jensen converted the crystalline barium acid salt to the sodium salt of heparin, which they subjected to elemental analysis. Results in good agreement with those of Charles and Scott were claimed w hen allowance was made for the hydration. Reinert and Winterstein also prepared heparin by the benzidine-salt procedure and obtained 25-50 mg. 

Fried and Wintersteiner first prepared a crystalline salt of streptomycin. Crude streptomycin phosphotungstate was converted to a crude picrate which was fractionated by flowing chromatography. One or more of the fractions, after removal of the picric acid, yielded a highly active amorphous product from which a crystalline streptomycin reineck-ate was obtained. 

Acid hydrolysis of streptomycin trihydrochloride yielded an optically inactive, strongly basic degradation product which was readily isolated and purified as its picrate. This base, designated streptidine, was also obtained as the crystalline sulfate (anhydrous and monohydrate forms), dihydrochloride, dihydriodide, carbonate, and a variety of other crystalline salts. Analytical data on all of these salts indicated the molecular formula C8Hi8Ne04-2HX. Fried, Boyack and Wintersteiner have described the free base. 

Fried and Wintersteiner - oxidized streptomycin trihydrochloride with bromine water to an amorphous, antibiotically inactive product The relatively strongly acidic nature of this substance, which they named streptomycinic acid, was demonstrated by electrometric titration. In the infrared spectral region the substance exhibited an absorption maximum at a wave length of 6.06m, which was partially displaced to 5.81m when the spectrum was observed in the presence of deuterium oxide and deuterium chloride. A shift of this type is usually found with dipolar ions and was taken therefore as an indication of the expected dipolar ion character of streptomycinic acid. 

Fried, Walz and Wintersteiner isolated 4-desoxy-i/-glycero-tetrose phenylosazone (XLII) from the reaction of streptobiosamine hydrochloride with phenylhydrazine and thus demonstrated that streptose was configurationally an l sugar. The levorotation ([a] o —37°, water ) of streptosonic acid monolactone (XXIII) might also be adduced as contributory evidence for the l configuration of the penultimate carbon of streptose, should Hudson s lactone rule be applicable to this rather complex structure. 

The solvent is removed on the water-bath, the residue is oxidised by means of a mixture of concentrated sulphuric acid, concentrated nitric acid and hydrogen peroxide, according to Winterstein s method, and the arsenic is determined in the solution obtained by the colorimetric method with mercuric chloride paper (see p. 326). 

The poisonous properties of the alkaloidal material obtained from the yew tree were first investigated by Borchers in 1876 [18], but its structural characterization was exceedingly slow, despite intensive work by numerous research groups. The first clue came only in 1923, when Winterstein, the chemist who coined the classical definition of an alkaloid, showed that taxine is the ester of a polyalkol esterified with acetic acid and (L)-P-dimethylamino-P-phenylpropionic acid [19], This P-aminoacid was then named after Winterstein. The early studies on taxine were... 

Winterstein esters easily undergo P-elimination to A -cinnamic acid esters (Scheme I). It is not dear to what extent this conversion is enzymatic or only chemical. The conversion can take place on storage [31] or in mild acidic medium. Prolonged times (months) are required with silica gel [32], With compounds of the taxine B-type, the reaction can take place fairly easily on plant storage, though the extent of this reaction in the seeds is much less [30], The degradation of Winterstein esters of the taxine B-type (2a-d) has a dramatic effect on the composition of taxine, since Winterstein esters of the 2 -deacetoxyaustrospicatine-type (40 and... 

Taxane alkaloids are made up of a terpenoid core and a phenylpropanoid (3-amino acid, joined by an ester bond. They can be classified according to the carbon-carbon connectivity of the terpenoid core and the type of the side-chain. Thus, the diterpenoid core can be of the taxane- (Tables 3-8), 11 (151 )abeotaxane-(Table 10), 2(3->20)abeotaxane-(Table 2) or 3-11-cyclotaxane (Table 9) type, whereas the side chain can be Winterstein s add [L(R) (3-dimethylamino-P-phenylpropionic add] or N, A/-dimethylphenylisoserine (2R, 3S (threo) a-hydroxy-3-dimethylamino-P-phenylpropionic acid). Further modification occurs in the... 

Taxine B-type (Table 3, 2a-d) the terpenoid core is normal (taxane) and bears a 13-oxo group, whereas the side chain is Winterstein s acid. Modification occurs by deoxygenation at C( 1) and in the acetylation pattern of the terpenoid core. 

A relationship seems to exist between the functionalization pattern of the terpenoid core and the type of side-chain. Thus, alkaloids of the 13-oxo type are generally esterified with Winterstein s acid, and those of the 2(3->20) abeo-type with phenylisoserine, whereas N-demethylation is observed mainly in alkaloids of the 13-acetoxyl type. 

The biogenesis of Winterstein s acid and phenylisoserine has been investigated in detail [42-43], These P-aminoacids are derived from phenylalanine, probably through a diotopic reaction involving the migration of the amino group from the a- to the P-carbon of the amino acid [44], Cinnamic acid was not incorporated in the yew P-amino acids [44],... 

Winterstein esters are easily turned into >-cinnamates by the action of acids (H silica gel) [32]. For preparative purposes the reaction has been carried out using the Hoffmann elimination of the corresponding methylammonium hydroxides [27] or the Cope elimination of the corresponding tf-oxides [SI], The latter procedure is more convenient, since, if the reaction is carried out in THF, elimination of dimethylhydroxylamine takes place spontaneously at room temperature. If only a moderate excess of peracid is employed, the exocyclic double bond at C-4 is not affected [30], The transformation of Winterstein esters into cinnamates can be very useful for separation purposes. Thus, whereas taxine B (2a) and isotaxine B (2b) are difficult to separate by HPLC, their corresponding cinnamates can be separated by column chromatography... 

Prolonged (ca 3 h) irradiation of Winterstein esters leds to the formation of the corresponding phenylpropionates [41] (Scheme 4) The reaction is typical of Winterstein s acid derivatives and does not involve antenna-like effects from chromophores on the terpenoid moiety. Similar results were obtained in fact with simple aliphatic esters of this P-aminoacid [41]. Under these conditions (irradiation for several hours), alkaloids of the lS-oxo.A4 20 11-taxadiene-type (taxine B and comptonine-type) undergo photocyclization to 3,11-cyclotaxanes [40], The photocyclization of this type of alkaloids could be accomplished without reductive deamination using shorter (17 min) irradiation times [S3]. 

Liquid uronititic iiiniiic i. for example aniline or lsiH iiinolinc, ofcen become badly discolored on storage us Ihc rcsull of air oxidation. Distillation from a pinch of zinc dust affords tdmost water-clear liquid. Kuhn and Winterstein" found that the violet carotinoid ester-acid bixin can be reduced very smoothly to its yellow dihydride with zinc dust in pyridine containing a small amount of acetic acid. Thus on addition of... 

The year 23004 marked the centenary of two important discoveries in the field of metabolism The discovery of beta-oxidation of fatty acids by Franz Knoop (1904), and the discovery of the oxygen dependence for normal pump function of the heart by Hans Winterstein (1904).2 The year 2004 also marked the 50th anniversary of the discovery, by Richard Bing and his colleagues, that the human heart prefers fatty acids for respiration.3... 

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