Thiazole-containing natural products

The relative and absolute stereochemistry of antimitotic macrolide archazolid A and B, originally isolated in the early nineties, has been determined on the basis of extensive high-field NMR studies, molecular modelling and chemical derivatization 06OL4751 . The proposed structures have yet to be confirmed by total synthesis. 

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Other examples of Ugi reactions combined with RCM have been described in the literature. Hebach and Kazmaier reported the synthesis of conformationally fixed cyclic peptides [70] and Beck and Domling synthesized biaryl-containing natural product-like macrocycles using this method [41]. The same group also reported combination of Passerini and Horner-Wadsworth-Emmons reactions to obtain butenolides [67] and another variation for the combinatorial synthesis of thiazoles [69]. 

During this time, the total synthesis of several marine sulfur-containing natural products cited in this review has been reported and they confirmed the suggested structures. This is the case of the synthesis of some sulfonoceramides (e.g. flavocristamide A (318) discussed in the sulfonic acid and their derivatives section [366], and the synthesis of the thiazole-containing compounds bistratamide D (381) [367], trunkamide (388) [368], mollamide (393) [369], dolastatin I (409) [370], and virenamide B (414) [371]. 

Of the many specific types of oxazoles, those bearing a 4-carboxy-derived group are of considerable importance. Among these compounds are several natural products, including many which contain this moiety, or the analogous thiazole group. 

MS has also been widely used to characterize thiazole-containing odors <2006EOC465>, flavors <2006EET675>, thiazole-metal complexes <2005ICA(358)2781>, natural products <2004JPS2953>, and protein-thiazole complexes <2004JME6658>. 

The thiazole ring is synthesized biochemically by enzymatic post-translational modifications of cysteine-containing peptides. Heterocyclization between cysteine side-chains and neighboring carbonyl groups produces dihydrohetero-aromatic thiazolines as initial products followed by a two-electron redox reaction yielding either thiazole or thiazo-lidine rings (Scheme 104). All three oxidation states are seen in natural products. 

The study of thiazoles and their derivatives has continued to flourish primarily due to their importance as both synthetic targets and drug candidates. This review chapter focuses on the syntheses and reactions of these 5-membered heterocyclic ring systems containing nitrogen and sulfur (or selenium or tellurium) (reported during 2005). The importance of these 7t-rich heterocycles in medicinal chemistry and natural products is also covered. 

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]. 

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