Thiazole 2-amino- from

Chemical manganese dioxide (CMD). This form of Mn02 is used for batteries it is available from I. C. Sample office (Cleveland, Ohio, 44101). Shioiri et al. report it is superior to commercial activated Mn02 (Aldrich) and more convenient than freshly prepared activated Mn02 for dehydrogenation of 2-(l-ami-noalkyl)thiazolidine-4-carboxylic acids to the corresponding thiazoles (thiazole amino acids). 

A thiazolium amino acid (Taz) has been developed which can be utilized to mimic TDP-dependent enzyme function [52]. In this strategy, illustrated in Fig. 15, the commercially available amino acid 4-thiazolylalanine is incorporated into peptides by solid phase peptide synthesis. Prior to deprotection of the amino acid side chains and cleavage of the peptide from the resin, the thiazole amino acid is alkylated with an alkyl halide to generate the corresponding thiazolium amino acid having various N3-substituents (BzTaz = 3-benzyl-Taz, NBTaz = 3-nitrobenzyl-Taz). 

Anthraquinoneazoles. In contrast to the older yellow Algol dyes, which contain two thiazole rings (e g., 2,2-bisanthra [2,1 d thiazole-6,11-quinonyl), the red to blue oxazoles and thiazoles derived from l-aminoanthraquinone-2-carboxylic acid and 3-amino-2-hydroxy- or -mercaptoanthraquinones exhibit good lightfastness. The good fastness to atmospheric conditions and chlorine of the blue deriv-... 

Table 1 2,3-Dihydrooxazoles and -thiazoles (6) from a-Amino Acids...

Enantiomerically pure thiazoline and thiazole amino acids can be synthesized by condensation reactions between cysteine esters and chiral imino ethers derived from amino acids (Scheme 110)... 

With the increasing importance of the need to discover new dmgs, considerable effort has been directed to identify a convenient method for rapidly preparing a large number of diverse molecules. To satisfy such keen demand, polymer-supported synthesis offers tremendous utility, and several methods have been developed to derive heterocyclic compounds based on a heterocyclization strategy. For example, Habermann et al. described a convenient method for preparing 2-amino-1,3-thiazole derivatives from a-bromoketone precursors by direct treatment with thiourea in refluxing THF in the presence of PS-TBD [63] (Scheme 6.15). 

The structure of the un-named alkaloid (19) obtained from a Thermoac-tinomyces strain has been confirmed by a simple synthesis from tryptamine and the thiazole amino-acid (20), prepared from (+)-(5)-alanine (Scheme 2). ... 

Further products prepared by the thionyl chloride method in solution are Dolastatin, a thiazole amino acid component (gln)Thz (70% yield) [1110], 4-phenyl-3-furoxanecarbonitrile (55% yield) [1111], ethyl 5-cyano-l-(l,l-dimethyl-ethyl)-lH-pyrazolo-4-carboxylate (61% yield) [1112], ethyl 2-anilino-4-chloro-5-cya-nothiophene-3-carboxylate (77% yield) [1113], and 4-cyanoisoxazole from its oxime tosylate (47% yield) [1114]. 

Amino-thiazole synthesis from a-aminonitriles and carbon disulfide, or carbon oxysulfide, isothiocyanate, dithioacids. 

If wewakazole contains oxazole amino acids, trichamide and venturamides A and B contain two thiazole amino acids. These compounds were isolated from Trichodesmium erythraeum and Oscillatoria sp. (Buenaventura Bay, Panama). Trichamide A is the first natural product to be isolated from T. erythraeum venturamides A and B have antimalarial activities, with IC50 values around 5 xM. 

The application of this technique has shown that, in most cases, thiazole amino acids have the absolute configuration R. If these thiazole amino acids are the result of cyclization/dehydration between an amino acid and a cysteine, oxazole amino acids may be formed from a serine through a similar mechanism. To facilitate the writing of formulas, the symbols Tzl (thiazole), Tzn (thiazoline), Ozl (oxazole) and Ozn (oxazoline) are often used, and, depending on the nature of the alkyl group, we add the symbol of the normal amino acid (o-LeuTzl, o-ValTzl,... 

Amino-4 -methylthiazole slowly decomposes on storage to a red viscous mass. It can be stored as the nitrate, which is readily deposited as pink crystals when dilute nitric acid is added to a cold ethanolic solution of the thiazole. The nitrate can be recrystallised from ethanol, although a faint pink colour persists. Alternatively, water can be added dropwise to a boiling suspension of the nitrate in acetone until the solution is just clear charcoal is now added and the solution, when boiled for a short time, filtered and cooled, deposits the colourless crystalline nitrate, m.p. 192-194° (immersed at 185°). The thiazole can be regenerated by decomposing the nitrate with aqueous sodium hydroxide, and extracting the free base with ether as before. 

Chapter V. Quinaldine (V,2) 2-methyl-, 2 5-dimethyl- and 2-acetyl-thiophene (V,8-V,10) 2 5-dimethyl and 2 4-dimethyl-dicarbethoxy-p3nrole (V,12-V,13) 2-amino- and 2 4 dimethyl-thiazole (V,15-V,16) 3 5-dimethyl-pyrazole (V,17) 4-ethylp3rridine (from pyridine) (V,19) n-amyl-pyridines from picolines) (V,28) picolinic, nicotinic and isonicotinic acid (V,21-V,22) (ethyl nicotinate and p-cyanop3n idine (V,23-V,24) uramil (V,25) 4-methyl-(coumarin (V,28) 2-hyi-oxylepidine (V,29). 

Diazo coupling involves the N exocyclic atom of the diazonium salt, which acts as an electrophilic center. The diazonium salts of thiazoles couple with a-naphthol (605). 2-nitroresorcinol (606), pyrocatechol (607-609), 2.6-dihydroxy 4-methyl-5-cyanopyridine (610). and other heteroaromatic compounds (404. 611) (Scheme 188). The rates of coupling between 2-diazothicizolium salts and 2-naphthol-3.6-disulfonic acid were measured spectrophotometrically and found to be slower than that of 2-diazopyridinium salts but faster than that of benzene diazonium salts (561 i. The bis-diazonium salt of bis(2-amino-4-methylthiazole) couples with /3-naphthol to give 333 (Scheme 189) (612). The products obtained from the diazo coupling are usuallv highly colored (234. 338. 339. 613-616). 

In the first chapter, devoted to thiazole itself, specific emphasis has been given to the structure and mechanistic aspects of the reactivity of the molecule most of the theoretical methods and physical techniques available to date have been applied in the study of thiazole and its derivatives, and the results are discussed in detail The chapter devoted to methods of synthesis is especially detailed and traces the way for the preparation of any monocyclic thiazole derivative. Three chapters concern the non-tautomeric functional derivatives, and two are devoted to amino-, hydroxy- and mercaptothiazoles these chapters constitute the core of the book. All discussion of chemical properties is complemented by tables in which all the known derivatives are inventoried and characterized by their usual physical properties. This information should be of particular value to organic chemists in identifying natural or Synthetic thiazoles. Two brief chapters concern mesoionic thiazoles and selenazoles. Finally, an important chapter is devoted to cyanine dyes derived from thiazolium salts, completing some classical reviews on the subject and discussing recent developments in the studies of the reaction mechanisms involved in their synthesis. 

In this chapter we intend to outline the general methods by which the thiazolic ring is synthetized from open-chain compounds. The conversion of one thiazole compound to another is not discussed here, but in appropriate later chapters. Thus the conversion of thiazole carboxylic acids, halogeno-, amino-, hydroxy-, and mercaptothiazoles, to the corresponding unsubstituted thiazoles is treated in Chapters IV through VII, respectively. 

The action of ammonia on N-(aryl-i,3-oxathiol-2-ylidine) tertiary im-inium salts (254) yields linear intermediates (255) that cyclize to 2-amino-4-phenyl thiazoles (256) on crystallization from acetic acid (Scheme 129) (730). 

The replacement of 2-amino group by a hydrogen can be achieved by diazotization, followed by reduction with hypophosphorous acid (1-8, 13). Another method starting from 2-aminothiazole is to prepare the 2-halo-thiazole by the Sandmeyer reaction (prepared also from the 2-hydroxy-thiazole), which is then dehalogenated chemically or catalytically (1, 9, 10). 

Thiostrepton family members are biosynthesized by extensive modification of simple peptides. Thus, from amino acid iacorporation studies, the somewhat smaller (mol wt 1200) nosiheptide, which contains five thiazole rings, a trisubstituted iadole, and a trisubstituted pyridine, is speculated to arise from a simple dodecapeptide. This work shows that the thiazole moieties arise from the condensation of serine with cysteiae (159,160). Only a few reports on the biosynthesis of the thiostrepton family are available (159,160). Thiostrepton is presently used ia the United States only as a poly antimicrobial vetetinary ointment (Panalog, Squibb), but thiazole antibiotics have, ia the past, been used as feed additives ia various parts of the world. General (158) and mechanism of action (152) reviews on thiostrepton are available. 

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