Pyridine-thiazole cores

Thiopeptide antibiotics are a class of highly modified macrocyclic sulfur-containing peptides, and nearly all the thiopeptide antibioties identified to date inhibit protein synthesis in bacteria. The Bohlmann-Rahtz pyridine synthesis is a useful methodology in the synthetic approach for thiopeptide antibiotics.For example, one-step Bohlmann-Rahtz assembly of 189 and 190 in the presence of ammonium acetate in acetic acid at reflux afforded the corresponding pyridine-thiazole cores of thiopeptide antibiotics 191 in 63% yield.The TBS protecting group was also replaced by an acetate, probably as a consequence of acid-promoted cleavage and consequent Fischer-type esterification of the liberated alcohol. 

V.S. Aulakh, M.A. Ciufolini, An improved synthesis of pyridine-thiazole cores of thiopeptide antibiotics, J. Org. Chem. 74 (2009) 5750-5753. 

As in the case of pyridine, the quaternization of thiazole induces a bathochromic shift of the UV absorption spectrum. In ethanol the long wavelength maximum at 233 nm (log e = 3.59) for thiazole moves to 240 nm (log s = 3.62) for 3-methylthiazolium tosylate. As in the case of the free bases, the substitution of a nuclear hydrogen atom by a methyl group induces a bathochromic shift that decreases in the order of the position substituted, 4- > 5- > 2-, and this perturbation could be accounted for by a theoretical model based on the PPP 7r method, using the fractional core charge approximation (72BSF3862). 

Amythiamicin D was the first in the family to be synthesized. The 2,3,6-trisubstituted pyridine core was synthesized from serine-derived l-alkoxy-2-azadienes and thiazoyl enamide dienophiles ultilizing a biosynthesis-inspired hetero-Diels-Alder route under MW irradiation. After successive incorporation of glycine and bis-thiazole fragments, amythismicin D was obtained by macrocyclization <2005JA15644, 2004CC946>. 

The Sommelet reaction has been widely extended to heterocycles, which are important to medicinal chemists. With yields ranging from 50% to 57%, aldehydes of pyridine, isoquinoline, and thiazole were prepared from the corresponding heteroarylmethyl bromides.27 5-Benzyloxy-3-bromomethyl-benzo[i]thiophene (30) was converted to 3-carboxaldehyde 31 in 40% yield.28 Thiazole 32 was the core structure in another Sommelet reaction to give 33 although in poor yield.29 In contrast, a different thiazole substrate 34 gave aldehyde 35 in 49% yield.30 Benzopyrans are also tolerated by the Sommelet reaction conditions.31,32 For example, substrate 36 was converted to aldehyde 37 in 58% yield.32... 

Cyclothiazomycin is 1 of 76 structurally distinct actinomycete thio-peptide antibiotics, can inhibit bacterial protein synthesis, and prevent the growth of gram-positive bacteria [38]. In 2011, Deiters and cowor-kers reported their work on the synthesis of the pyridine core of cyclothiazomycin based on ruthenium-catalyzed [2 + 2 + 2] cyclotri-merization as the key step (Scheme 3.17) [39]. The electron-deficient nature of the thiazole-bearing nitrile enables ruthenium catalysis under mild reaction conditions with excellent yields. Complete chemo and regioselectivity in the construction of the trisubstituted pyridine core were achieved by applying a temporary silyl tether. 

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