Thiazole ring, 2-amino- from

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. 

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. 

In NRPs and hybrid NRP-PK natural products, the heterocycles oxazole and thiazole are derived from serine and cysteine amino acids respectively. For their creation, a cyclization (or Cy) domain is responsible for nucleophilic attack of the side-chain heteroatom within a dipeptide upon the amide carbonyl joining the amino acids [61]. Once the cyclic moiety is formed, the ring may be further oxidized, to form the oxazoline/thiazoline, or reduced, to form oxazolidine/thiazolidine (Figure 13.20). For substituted oxazoles and thiazoles, such as those... 

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-... 

Fig. Vl-4. Geometry of thiazole ring in 2-amino-4-phenylthiazole hvdrobromide. Italicized values are interatomic distances (A) other numbers are angles in degrees. From Ref. ]42.

A large variety of macrolides have been isolated from natural sources. Macrolides have various ring sizes up to 62 and exhibit various characters spiroacetal-fused macrolides, polyene macrolides, macropolylides, and macrolides containing amino nitrogen, amide nitrogen, oxazole rings, or thiazole rings in their skeletons. 

On the other hand, thiazolo[5,4-d] pyrimidines also obtained from 5-aminothiazole derivatives, are prepared from aminomalononitrile (or its derivatives) and isothiocyanates [141] or thioesters [142]. The next to 5-amino and 4-cyano (or conforming carboxamide or ester groups) on the thiazole ring are proper functionalities to concept a fused pyrimidine ring system. 7-Aminothiazolo[5,4-d]pyrimidines can be prepared from 5-amino-4-cyanothiazoles by reaction... 

Other heterocyclic rings appear in biological systems. Thiamin (131) contains a thiazole ring as well as a pyrimidine ring, and it is an essential component of the human diet. Thiamin is a water-soluble vitamin of the B complex (vitamin Bj). Although humans cannot synthesize thiamin, many bacteria synthesize it and use it in the form of thiamin pyrophosphate. Bacillus subtilis produces thiamin by a biosynthetic route, but it also synthesizes the thiazole unit (142) found in 131 from the amino acid glycine (133 see Chapter 27, Section 27.3.2) and l-deoxy-d-xylulose-5-phosophate, 132.2 (See Chapter 28, Section 28.1, for an introduction to sugars such as xylulose.)... 

According to Breslow, the active aldehyde intermediate in the decarboxylation of pyruvate could be an a-hydroxyethyl derivative of thiamine pyrophosphate, the substituent being attached in position 2 to the thiazole ring . His starting point was the observation that thiazolium salts easily lose a proton at C-2. Thus a stable and reactive zwitterion results that could be capable of forming an acyl carbanion derivative. The near-by amino-pyrimidine ring would have an inductive effect upon electron withdrawal at C-2. Breslow pictures the formation of acetoin from pyruvate and acetaldehyde as follows ... 

Imine formation between pyruvate and the amino substituent in the pyrimidine ring was at one time suggested as a possible step in decarboxylation but this idea has since been abandoned. The reaction is > now believed to involve nucleophilic attack on the carbonyl carbon of i pyruvate by an anion formed by loss of a proton from the C(2> position 5 in the thiazole ring. Details of the mechanism need not concern us t since no amino group is involved in either the substrate or the co- j factor. 

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