Oxazole amino acids

The total synthesis of the peptide derived macrocycle dendroamide A 163 has been accomplished in 19% overall yield from appropriately protected heterocyclic amino acids. The oxazole amino acid 162 resulted from cyclodehydration of P-ketodipeptide 161 with bis(triphenyl)oxodiphosphonium triflate, with notable chemo- and stereoselectivity <03JOC9506>. 

The first synthesis of dendroamide A106 was achieved by Bertram and Pattenden [153] followed by reports from other research groups [154], The synthetic route was designed based on the disconnection point A (Figure 8.5). The oxazole amino acid 109 was prepared from oxidation of 107, and subsequent cyclization followed by deprotection of the Z group (Scheme 8.8). In parallel, thiazole derivative... 

If wewakazole contains oxazole amino acids, trichamide and venturamides A and B contain two thiazole amino acids. These compounds were isolated from Trichodesmium erythraeum and Oscillatoria sp. (Buenaventura Bay, Panama). Trichamide A is the first natural product to be isolated from T. erythraeum venturamides A and B have antimalarial activities, with IC50 values around 5 xM. 

The application of this technique has shown that, in most cases, thiazole amino acids have the absolute configuration R. If these thiazole amino acids are the result of cyclization/dehydration between an amino acid and a cysteine, oxazole amino acids may be formed from a serine through a similar mechanism. To facilitate the writing of formulas, the symbols Tzl (thiazole), Tzn (thiazoline), Ozl (oxazole) and Ozn (oxazoline) are often used, and, depending on the nature of the alkyl group, we add the symbol of the normal amino acid (o-LeuTzl, o-ValTzl,... 

Thiazole and oxazole amino acids of cyclic peptides of Dideminidae... 

Azolecarboxylic acids can be quite strongly acidic. Thus l,2,5-thiadiazole-3,4-dicar-boxylic acid has first and second values of 1.6 and 4.1, respectively <68AHC(9)107). The acidic strengths of the oxazolecarboxylic acids are in the order 2>5>4, in agreement with the electron distribution within the oxazole ring <74AHC( 17)99). Azolecarboxylic acids are amino acids and can exist partly in the zwitterionic, or betaine, form e.g. 394). 

Oxazol-5(2H)-one, 2-benzylidene-4-methyl-tautomerism, 6, 186 Oxazol-5(2ff)-one, 2-methylene-isomerization, 6, 226 Oxazol-5(2H)-one, 2-trifluoromethyl-acylation, 6, 201 Oxazol-5(4ff)-one, 4-allyl-thermal rearrangements, 6, 199 Oxazol-5(4H)-one, 4(arylmethylene)-Friedel-Crafts reactions, 6, 205 geometrical isomerism, 6, 185 Oxazol-5(4ff)-one, 4-benzylidene-2-phenyl-configuration, 6, 185 photorearrangement, 6, 201 Oxazol-5(4ff)-one, 4-benzyl-2-methyl-Friedel-Crafts reactions, 6, 205 Oxazol-5(4ff)-one, 4-methylene-in amino acid synthesis, 6, 203 Oxazol-5(4ff) -one. 2-trifluoromethyl-hydrolysis, 6, 206 Oxazolones... 

More recent examples have employed a milder reagent system, triphenyl-phosphine and dibromotetrachloroethane to generate a bromo-oxazoline, which is subsequently dehydrohalogenated. Wipf and Lim utilized their method to transform intermediate 11 into the 2,4-disubstituted system of (+)-Hennoxazole k Subsequently, Morwick and coworkers reported a generalized approach to 2,4-disubstituted oxazoles from amino acids using a similar reagent combination, triphenylphosphine and hexachloroethane. ... 

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... 

Conceptually interesting is the synthesis of the oxazole system 94 through a Beckmann rearrangement of a-formyl ketoxime dimethyl acetals 93 which demonstrated the possibility of a non-amino acid pathway in the biosynthesis of marine derived oxazoles <06CC1742>. 

Strecker aldehyde are generated by rearrangement, decarboxylation and hydrolysis. Thus the Strecker degradation is the oxidative de-amination and de-carboxylation of an a-amino acid in the presence of a dicarbonyl compound. An aldehyde with one fewer carbon atoms than the original amino acid is produced. The other class of product is an a-aminoketone. These are important as they are intermediates in the formation of heterocyclic compounds such as pyrazines, oxazoles and thiazoles, which are important in flavours. 

The rhodium acetate complex catalyzed the intramolecular C-H insertion of (/ )-diazo-fR)-(phenylsulfonyl)acet-amides 359 derived from (f )-amino acids to afford in high yield the 6-benzenesulfonyl-3,3-dimethyl-7-phenyl-tetrahydro-pyrrolo[l,2-c]oxazol-5-one 360 (Equation 63) <2002JOC6582, 2005TL143>. 

The first syntheses of a-allenic a-amino acids [131,133] took advantage of Steg-lich s [134] protocol for the oxazole-Claisen rearrangement of unsaturated N-ben-zoylamino acid esters (Scheme 18.46). Thus, treatment of the propargylic ester 143 with triphenylphosphine and tetrachlormethane furnished the allenic oxazolone 144, which was converted into the amino acid derivative 145 by methanolysis. Stepwise deprotection finally led to the allenic DOPA analog 146, which shows a much higher decarboxylase-inhibiting activity than a-vinyl- and a-ethynyl-DOPA [133],... 

P Wipf, H Heimgartner. Coupling of peptides with C-terminal a,a-disubstituted a-amino acids via oxazol-5(4//)-onc. Ilelv Chim Acta 69, 1153, 1986. 

F Weygand, W Steglich, X Boracio de la Lama. On the sterical course of the reaction of oxazol-5-ones with amino-acid esters. Tetrahedron Suppl 8, part 1, 9, 1966. 

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. ... 

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]. 

In a similar way, propargyl esters of A -benzoyl-a-amino acids have been converted into a-allenyl-a-amino acid esters 113 by cyclization to oxazoles 111 followed by Claisen rearrangement to the 4-allenyl-2-phenyl-5(4//)-oxazolones 112. Oxazolone ring opening with methanol then afforded 113 (Scheme 7.32). ... 

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