Thiazole ring assembly

The thiazole ring is assembled on the 5-carbon backbone of 1-deoxyxylulose 5-phosphate, which is also an intermediate in the alternative biosynthetic pathway for terpenes (Fig. 22-2) and in synthesis of vitamin B6 (Fig. 25-21). In E. coli the sulfur atom of the thiazole comes from cysteine and the nitrogen from tyrosine.374 The same is true for chloroplasts,375 whereas in yeast glycine appears to donate the nitrogen.372 The thiamin biosynthetic operon of E. coli contains six genes,372a 376 one of which (ThiS) encodes a protein that serves as a sulfur carrier from cysteine into the thiazole.374 The C-terminal glycine is converted into a thiocarboxylate ... 

The thiazole ring of the 5-(D-arahfno-tetritol-l-yl)-imidazo[2,l-6]thiazol-ium olate 160 was assembled onto the imidazole ring of 4-(tetra-0-acetyl-D-flrabino-tetritol-l-yl)imidazoline-2-thione (156) by reaction with 2-bromophenylacetic acid (91MI7) (Scheme 47). 

The reaction has been employed in several molecules in drug discovery and development. For example, Ikemoto et al. have developed a practical route to a thiazole as part of their efforts toward a kilogram-scale synthesis of a P-adrenergic receptor agonist as a candidate for tihie treatment of obesity. The thiazole ring was assembled by allowing the haloketone and thioamide to react. 

The penem system has always been assembled by late formation of the thiazoline ring. No attempt to obtain penems by closing the azetidinone ring as the last step has ever been reported, though this strategy is well documented on penicillins [3, 4]. Approaches based either on the dehydrative condensation of thiazoline acetic acids 4 or on ketene addition to thiazoles 5, reactions known to... 

Poly(3-alkylthiophene)s, having TT and electron-deficient thiazolo[5,4-J]thia-zole rings, were assembled through Stille cross-couplings (Scheme 27) [49]. Treatment of the aldehydes 122 with dithiooxamide (123) provided thiazolo[5,4-d] thiazole oligomers (124). Dibromination and then copolymerization with bis-stannane 126 produced air-stable polymers 127a-c. 

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