Thiazoles from thiazolidines

Thiazolidine-2-thione, 4-hydroxy-synthesis, 6, 314 Thiazolidinethiones tautomerism, 6, 273 1,2,4-thiazoles from, 5, 776 Thiazolidine-2-thiones reactions... 

The oxidation state of thiazolines and oxazolines can be adjusted by additional tailoring enzymes. For instance, oxidation domains (Ox) composed of approximately 250 amino acids utilize the cofactor FMN (flavin mononucleotide) to form aromatic oxazoles and thiazoles from oxazolines and thiazolines, respectively. Such domains are likely utilized in the biosynthesis of the disorazoles, " diazonimides, bleomycin, and epothiolone. The typical domain organization for a synthetase containing an oxidation domain is Cy-A-PCP-Ox however, in myxothiazol biosynthesis one oxidation domain is incorporated into an A domain. Alternatively, NRPSs can utilize NAD(P)H reductase domains to convert thiazolines and oxazolines into thiazolidines and oxazolidines, respectively. For instance, PchC is a reductase domain from the pyochelin biosynthetic pathway that acts in trans to reduce a thiazolyinyl-Y-PCP-bound intermediate to the corresponding thiazolidynyl-Y-PCP. ... 

An alternative procedure using A -bromosuccinimide in carbon tetrachloride was reported to provide thiazole 98 from thiazolidine 99 in 48% yield (Scheme 34) <2005JME2584>. 

Thiazoles can be prepared from thiazolines by oxidation with activated manganese dioxide. This approach has been applied to the synthesis of dimethyl sulfomycinnamate (11 to 12) <05JOC1389>, the polyoxazole-thiazole based cyclopeptide YM-216391 (13 to YM-216391) <05CC797>, and didmolamides A and B (14 to 15) <05TL2567>. A facile preparation of thiazole 17 from thiazolidine 16 involves a brornmation-elirnination protocol <05JMC2584>. 

Thiazoles (65) can be prepared from thiazolidines (64) by column dehydrogenation using manganese dioxide as the column support <97JPR96>. 

This volume is intended to present a comprehensive description of the chemistry of thiazole and its monocyclic derivatives, based on the chemical literature up to December, 1976. It is not concerned with polycyclic thiazoles, such as benzo- or naphthothiazole, nor with hydrogenated derivatives, such as thiazolines or thiazolidines later volumes in this series are devoted to these derivatives. The chemistry of thiamine has also been excluded from the present volume because of the enormous amount of literature corresponding to the subject and is developed in another volume. On the other hand, a discussion of selenazole and its monocyclic derivatives has been included, and particular emphasis has been given to the cyanine dyes derived from thiazolium salts. 

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... 

Dimethyl-3,5-dimethyl-l//,3//-pyrrolo[l,2-r ][l,3]thiazole-6,7-dicarboxylate 399 (R = H) was prepared from cysteine 396 using the method developed of Padwa et al. <1989JOC644>. The thiazolidine carboxylic acid 397 (R = H), obtained by reaction of the cysteine with formaldehyde, was heated in the presence of acetic anhydride and DMAD to give the sulfide 399 by dipolar cycloaddition of the acetylene to the intermediate dipole 398 (Scheme 59) <2002J(P1)1795>. 

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). 

In NRPS, the cyclization domain catalyzes cyclization of the side-chain nucleophile from a dipeptide moiety such as AA-Ser or AA-Cys (AA = amino acids) to form a tetrahedral intermediate, followed by dehydration to form oxazolines and thiazolines (Scheme 7.1) [20]. The synthesis of a 2-methyl oxazoline from threonine follows a similar mechanism. Once a heterocycle is formed, it can be further modified by reductase to form tetrahydro thiazolidine in the case of pyochelin biosynthesis. Conversely, oxidation of the dehydroheterocycles lead to heteroaro-mahc thiazoles or oxazoles as in the case of epothilone D (Figure 7.2) [21]. 

Methyl 3- /7/-D-daunosaminide 154 has been derived from d-149 via a Wittig-type olefination using (2-thiazolylmethylene)triphenylphosphorane (Scheme 13.53). A 1 1 mixture of (E)- and (Z)-alkenes is obtained, which is isomerized in the presence of iodine into a 9 1 mixture of ( )-152 and (Z)-152. Methylation of the thiazole moiety increases the electrophilicity of the alkene, which then accepts nucleophiles such as benzylamine. The adduct is treated with NaBH4 to give a thiazolidine. Acetylation and mercury-mediated hydrolysis of the thiazolidine ring generates 153, which, on acidic treatment in methanol, yields the A-benzyl 3- /7/-D-daunosaminide 154 [99]. 

The product with m.p. 83,5—84.5° C which Jacobson isolated appears to have been 3,4,4-trialkyl thiazolidin-5-one-2-thione rather than l,5,5-trimethylimidazolidine-2,4-dithione. The former can be synthesized independently from a-(methylamino) isobutyric acid and carbon disulfide (see also V.3). Other a-(methylamino) nitriles when refluxed with carbon disulfide, also yield 3,4,4-trialkyl-5-imino thiazol-idine-2-thiones (CLXII) (listed in Table 23) which can be hydrolyzed... 

The three 1,3-azoles, imidazole, thiazole and oxazole, are aU very stable compounds that do not autoxidise. Oxazole and thiazole are water-miscible liquids with pyridine-like odours. Imidazole, which is a solid at room temperature, and 1-methylimidazole are also water soluble, but are odourless. They boil at much higher temperatures (256 °C and 199 °C) than oxazole (69 °C) and thiazole (117 °C) this can be attributed to stronger dipolar association resulting from the very marked permanent charge separation in imidazoles (the dipole moment of imidazole is 5.6 D cf. oxazole, 1.4 D thiazole, 1.6 D) and for imidazole itself, in addition, extensive intermolecular hydrogen bonding. The dihydro- and tetrahydro-1,3-azoles are named imidazoline/imidazolidine, thiazoline/thiazolidine and oxazoline/oxazolidine. 

The discovery of tp o-displacement of silicon from the thiazole 2-position under mild conditions led to the development of this reaction as an essential component of a route to complex aldehydes. Subsequent qua-temisation, saturation of the heterocyclic ring using sodium borohydride, and then mercury(II)- or copper(II)-catalysed treatment leads to the destruction of the thiazolidine and the formation of a new, homologous aldehyde an example is shown below." " ... 

Heterocydes are common motifs in natural products, which may occur as single, tandem, and multiple moieties within a given molecule (Scheme 8.5) [35-37]. These motifs often provide molecular interaction with nudeotide and protein targets. In the biosynthesis of NRPs, an oxazoline was usually formed from a dipeptide containing serine in the second position upon dehydration (Scheme 8.5) [38]. The syntheses of a thiazoline from cysteine and a 2-methyloxazoline from threonine follow a similar mechanism. These heterocycles can be further custom-made to provide thiazolidines/oxazolidines upon reduction or thiazoles/oxazoles upon oxidation. Enzymatic heterocyclization can be portable, as demonstrated in the synthesis of novel chiral heterocyclic carboxylic adds by hybrid enzymes [39]. 

This type of cyclization has been used mainly to prepare imidazo[2,l-fe]thiazoles and imidazo[l,2-6]pyrazoles (Schemes 13 and 14). Base-catalyzed cyclizations of 2-(cyanoimino)thiazolidines (124) afforded imidazo[2,l-6]thiazoles (126) via intermediates (125). Cyclization of (124) only occurs when R is an electron withdrawing group <885261 >. Imidazo[l,2-6]pyrazoles have been prepared from suitably substituted imidazolidine derivatives <80JHC1413>. The imidazolidine (127), prepared in 5 stages from 2-imidazolidine thione, was subjected to a hydrazinolysis reaction initiated by 2,4-dinitrophenylhydrazine to give a mixture of imidazo[l,2-fe]pyrazoles (129) and (130) and the hydra-zone (128). 

---