2-Amino-13-oxazoles

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>. 

Chattopadhyay and Pattenden first demonstrated the viability of such a synthetic strategy in a model system designed to construct the basic tris-oxazole core. The oxazole amino alcohol 1573 was prepared from Gamer s acid " 1572 in four steps (Scheme 1.401). Serine benzyl ester was the starting material for 2-(acetoxymethyl)-4-oxazolecarbonyl chloride 1574. Acylation of 1573 with 1574 produced the bis-oxazole amide 1575. The differentially functionalized model tris-oxazole 1576 was then prepared from 1575 in two straightforward steps. 

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... 

Oxazoles preferred in practice bear 5-ethoxy- or 5-cyanosubstituents. Other alkoxy (39—42), trimethylsilyloxy (43), alkythio (44), amino (45), and... 

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 at least one case, the standard Bucherer-Bergs conditions gave rise to oxazole rather hydantoin. Specifically, when 5-benzyloxy-pyridine-2-carbaldehyde (11) was treated with potassium cyanide, ammonium chloride, and ammonium carbonate in boiling ethanol/water, 5-amino-oxazol-2-ol 12 was obtained. Subsequent heating of oxazole 12 with acetic acid at reflux overnight then produced the Bucherer-Bergs product, hydantoin 13. ... 

Some data were obtained from the photochemical isomerization of amino-isoxazoles. 5-Aminoisoxazoles gave the corresponding azirine (Scheme 21) [70JCS(C)1825] when a4-carboethoxy-substituted derivative was used, no azirine was isolated and the oxazole was the only product obtained (Scheme 21) (72CB748). The azirine intermediate was not observed upon irradiating 3-amino derivatives [91H(32)1765]. 

The diazotization of heteroaromatic amines is basically analogous to that of aromatic amines. Among the five-membered systems the amino-azoles (pyrroles, diazoles, triazoles, tetrazoles, oxazoles, isooxazoles, thia-, selena-, and dithiazoles) have all been diazotized. In general, diazotization in dilute mineral acid is possible, but diazotization in concentrated sulfuric acid (nitrosylsulfuric acid, see Sec. 2.2) or in organic solvents using an ester of nitrous acid (ethyl or isopentyl nitrite) is often preferable. Amino derivatives of aromatic heterocycles without ring nitrogen (furan and thiophene) can also be diazotized. 

N-Carboxy-a -amino-carbonsaure-anhydride (Leuchs-Anhydride, 2,4-Dioxo-tetrahy-dro-l,3-oxazole) werden durch Lithiumalanat reduktivzu 2-Amino-alkoholen (neben wenig N-Formyl-aminosaure) aufgespalten z.B.2 ... 

Cyclische 0,N-Acetale vom Typ der 1,3-Oxazolidine und 2,5-Dihydro-l,3-oxazole werden durch Lithiumalanat7 und Natriumboranat8,9 zu 2-Amino-alkoholen reduziert. Aus 3-Methyl-2-phenyl-l,3-oxazolidin wird z.B. mit Natriumboranat 2-(N-Methyl-N-benzyl-amino)-athanol (74% d.Th) erhalten8 ... 

Bei —0,15 bis -0,4 V entsteht 3-Hydroxy-(naphtho-[ ,2-c]-oxazol) bzw. I-Hydr-oxy- (naphtho-[2,l-c]-l,2-oxazol) aus l-Nitro-2-aminocarbonyl- bzw. 2-Nitro-l-amino-carbonyl-naphthalin5 ... 

Analog reagieren 3-Nitro-2-aminocarbonyl- und 8-Nitro-l-aminocarbonyl (bzw. carboxy)-naphthalin5 zum 1 -Hydroxy-(naphtho-[2,3-c -1,2-oxazol) bzw. 8-Amino-naphthalin-1 -carbonsaure-lactam ... 

Furthermore, oxazoles of type 9-82 bearing a secondary amino functionality can be converted into pyrrolo[3,4-b]pyridines 9-86 by reaction with appropriate acid chlorides 9-83 in a triple domino process consisting of amide formation/hetero Diels-Alder reaction and retro-Michael cycloreversion via 9-84 and 9-85 (Scheme 9.17). The pyrrolo[3,4-fc]pyridines can be obtained in even higher yields when the whole sequence is carried out as a four-component synthesis in toluene. Here, 1.5 equiv. NH4C1 must be added for the formation of the now intermediate oxazoles [56b]. 

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... 

Dimethoxybenzoyl chloride Benzoyl chloride, 2,3-dimethoxy- (9) (7169-06-4) 2-Amino-2-methyl-1-propanol 1-Propanol, 2-amino-2-methyl- (8,9) (124-68-5) 2,2 -Dimethoxy-6-(4 ,4 -dimethyloxazolinyl)biphenyl Oxazole, 2-(2 ,6-dimethoxy[1,1-biphenyl]-2-yl)-4,5-dihydro-4,4-dimethyl- (9) (57698-39-7)... 

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>. 

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