Thiazoles moiety

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. 

Another antiulcer histamine Hj receptor antagonist containing a thiazole moiety is zalb-dine (131) Its synthesis can be accomplished readily by brominating 4 acetyl 2 methylimidazole (129) to give haloketone 130 Displacement with amidinothiourea completes the synthesis of zaltidme (131) via a displacement cyclodehydration sequence [45]... 

An extract from the soluble stromal proteins of purified and intact spinach-leaf chloroplasts was prepared by lysis of the cells in buffer, centrifugation of the suspension of broken cells, and concentration of the supernatant with removal of insoluble material. This extract contained all of the enzymes involved in the condensation of the cyclic moieties of thiamine, thiazole, and pyramine. Thus, the synthesis of thiamine in this extract following the addition of pyramine and putative precursors was a proof that the system had the possibility of building the thiazole. It was found that L-tyrosine was the donor of the C-2 carbon atom of thiazole, as in E. coli. Also, as in E. coli cells, addition of 1 -deoxy-D-f/irco-pen-tulose permitted synthesis of the thiamine structure. The relevant enzymes were localized by gel filtration in a fraction covering the 50- to 350-kDa molecular-mass range. This fraction was able to catalyze the formation of the thiazole moiety of thiamine from 0.1 -mM 1-deoxy-D-t/ireo-pentulose at the rate of 220 pmol per mg of protein per hour, in the presence of ATP and Mg2+. 

Oxidation of thiazoles 137 with HOF MeCN provides easy access to the family of thiazole A-oxides 138 <06CC2262>. The readily made HOF MeCN complex, considered to be one of the best oxygen transfer agents in chemistry, transfers an oxygen atom directly to thiazole-containing compounds without affecting the double bonds of the thiazole moiety. A small amount of /V,SVS -trioxide 139 is also formed in this oxidation. 

Thiazole moiety of thiamin diphos phate cofactor... 

Modification of the field of 2,2/-bipyridine by replacement of one or both of the pyridine rings with five-membered heterocycles is a much more effective means of generating the crossover situation than replacement by six-membered rings. This has resulted in the crossover region being attained in a relatively large number of instances. The incorporation of thiazole moieties il-... 

Thiamine contains a pyrimidine moiety (A) and a thiazole moiety (B), joined by a methylene bridge as shown in (I). Microorganisms which... 

Xi, J., Ge, Y., Kinsland, C., McLaeeerty, F. W., and Begley, T. P. Biosynthesis of the thiazole moiety of thiamin in Escherichia coli identification of an acyldisulfide-linked protein-protein conjugate that is fimctionally analogous to the ubiquitin/El complex, Proc Natl Acad Sci USA 2001, 98, 8513-8518. 

A similar approach, outlined in Scheme 67, was disclosed by Danishefsky, using diene-ene methyl and trifluoro-methylketones 336a and 336b as the RCM substrates.Treatment of 336 in refluxing toluene with catalyst G for a few minutes afforded exclusively ( )-isomers 337 in high yield. The thiazole moiety was then installed... 

Dwivedi and Arnold (89) determined the thiazole moiety in thiamine by derivatizing first to form the TMS analog. Samples were chromatographed on 3% OV-17 on Chromosorb G (DMCS treated) at 110°C. Vitamin D2 (calciferol) and its analog Vitamin have been the subject of many applications in GC analyses. The compounds have been derivatized as the TMS analog and chromatographed on OV-17 (90) and SE-30 (91) and on 3% silicone on Celite after treatment with antimony trichloride (92). Several references to vitamine E (oi-tocopherol) are included in the review by Kern et al. (39) on GLC determinations of pharmaceuticals and drugs. The acetate was determined on 3% OV-17 on Chrom W-HP at 280°C. Vecci and Kaiser (93) determined Vitamin C as the TMS derivative on 3% SE-30 or 10% XE-60 on Anachrom ABS. Column... 

A series of macrolides bearing a thiazole moiety have been isolated from tunicates and sponges. The tunicate Lissoclinum patella has afforded the patellazoles A-C (428-430), which were found to be potent cytotoxins in the NCI human cell line protocol with mean IC50 values of 10-3—10-6 pg/ml as well as exhibiting antifungal activity [334, 335]. Furthermore, patellazole B (429) exhibited very potent antiviral activity against Herpes symplex viruses [334],... 

A (3-lactam ring substituted by a thiazole moiety has been reported to be formed simultaneously and under mild condition during the course of a multicomponent reaction [200]. When the 3-dimethylamino-2-isocyanoacrylate was reacted with the aldehyde in the presence of a (3-aminothiocarboxylic acid, substituted l-thiazole-2-yl-methyl-azetidin-2-one was smoothly formed (Scheme 92). Plausible reaction intermediates have been proposed. 

Scheme 92 Simultaneous assembly of [1-lactam and thiazole moiety by a multicomponent reaction...

An interesting approach to directly linked C-disaccharides 2-191 was developed by Dondoni et al. [171] via a hetero Diels-Alder reaction of sugar derived 1-oxa-1,3-butadienes as 2-190 bearing a thiazole moiety at position 2 as activating group (Fig. 2-54). 

We begin our discussion of the retrosynthetic fragments with the thiazole moiety A (cf. Scheme 1), i.e. the least problematic building block. Indeed, they appear to be so easily accessible that some authors do not mention their synthesis or references, and sometimes even forget to count the necessary steps in their final eonelusion. 

Two different strategies for the incorporation of the thiazole moiety were used so far either Stille coupling reactions of 4-stannylthiazoles by one group [18, 19] or Wittig-type ole-fination reactions by all others. The latter approach requires either 2-methyl-thiazole-4-carbaldehyde (4, Scheme 1) available from the corresponding ester by reduction [13, 20, 29, 30] or suitable 4-phosphorusmethyl derivatives (3a-d. Schemes 1 and 4) for the more common inverse approach. 

Thiamine is a water-soluble vitamin and is also known as vitamin Bi, or aneurin (Fig. 1). Both the pyrimidine and thiazole moieties are necessary for biological activity, which is maximal when only one methylene group bridges the two moieties. 

There are two classes of thiaminase. Thiaminase I catalyzes a base exchange reaction between the thiazole moiety of thiamin and a variety of bases, commonly primary, secondary, or tertiary amines, but also nicotincimide and other pyridine derivatives, and sometimes proline tmd sulfhydryl compounds. Thiaminase I is relatively widespread in a veuiety of microorgcmisms, plcmts, cmd fish. In addition to depleting thiamin, the products of base exchange catedyzed by thiaminase I eire structured emedogs of the viteimin and may have antagonistic effects (Edwin and Jackman, 1970). Similarly, the neurotoxic effects of the antibiotic metronidazole, which is a thiazole, may be fi om its activity as a substrate for thieiminase I, forming thiamin antimetabolites (Alston emd Abeles, 1987). 

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