Tetronic acid derivatives

The allylation reaction of the optically active tetronic acid derivatives 146 was shown to give a variety of isomers depending on the reaction conditions (temperature and reaction time) (Scheme 44 and Table I) (99H1321). The reaction is carried out by treating 146 with allyl bromide in DMF and in the presence of K2CO3. 

Effenberger and coworkers have utilized the tolerance of methyl ketones by the recombinant enzyme to develop an alternative synthesis of tetronic acids and their amino derivatives, as shown in Figure 5.18. Treatment of O-acyl cyanohydrins with lithium disilazide resulted in base-induced ring closure to amino tetronic acid derivatives. Alternatively, the cyanohydrins could be converted to a-hydroxy esters prior to acylation, and the same base-induced cyclization then led to tetronic acid derivatives [89]. 

Allylations at oxygen are the rule with alkyl halide-base systems. However, ascorbic acid 33, which is a tetronic acid derivative, has been allylated... 

The enolic thiofuranone derivatives 35 (e.g. R = n-propyl and R = n-decyl) and 36 are also inhibitors of fatty acid synthase and have served as drug leads against Plasmodium falciparum (malaria) and Trypanosoma (sleeping sickness) . Several tetronic acid derivatives exhibit significant inhibition toward bacterial peptidoglycan synthesis (K = 0.19 p.M for the derivative R = 2-naphthalene and (R, R ) = vinyl-1-naphthalene in equation 8 analogous to 39) . ... 

The lithium enolates from tetronic acid-derived vinylogous urethanes have been generated and their reactivity investigated with a variety of electrophiles (eq 5). The reactions proceed with excellent regio- and diastereoselectivity and a variety of alkylating agents can be utilized. 

Cyclic phosphate mimics tetronic acid derivatives... 

Other docking studies have been completed with tetronic acid derivatives in the active site of VHR results indicate that on dissociation, the 3-acyltetronic acid anion can bind tightly to the active site through several hydrogen bonds in a manner similar to that of phosphotyrosine (43). Finally, rhodanine and thiazolidinone cores have been shown to bind at or near the phosphate-binding site in modeling studies of various proteins (57), and they share many commonalities with compounds believed to mimic the pentavalent transition state of phosphate hydrolysis. Core structure electron-density isosurfaces for both rhodanine and thiazolidinone portray this well, as compared with the electron density structure of dissociated dimethyl phosphate. At this time, crystal structures of proteins complexed with these novel cyclic phosphate mimics have not been published. 

The first synthesis of phenylhydrazone 56 by the reaction of benzene diazonium chloride on 57 (37NI58, 37ZPC34) was similar to that used for tetronic acid derivatives. The later could be prepared from 55 through the sequence shown in Scheme 12 (35HCA602 36CB879). 

A. S. Shawali, I. M. Abbas, N. F. Abdelfattah, and C. Parkanyi, A theoretical study of tautomerism in dehydroascorbic acid osazone and related tetronic acid derivatives, Carbohydr. Res., 110 (1982)... 

The relative asymmetric induction observed in the rearrangement of cyclic substrates is also moderate. Thus, the selectivity for the thermal rearrangement of tetronic acid derivatives 5 ranges from 88% to 74% ds630. 

The lithium enolate derived from angelica lactone (LDA, THF, - 78 °C) reacts as a Michael acceptor exclusively at the y-position thus the butenolide (65) is obtained from ethyl acrylate. Surprisingly, in view of this finding, reaction with methyl iodide results in mixtures of the a-methyl and aa-dimethyl derivatives. Similar results have been obtained with the enolates of 2- and 3-methylbut-2-enolides which undergo prenylation by dimethylallyl bromide at both the a- and y-positions. By contrast the tetronic acid derivative 3-methoxy-2-methylbut-2-enolide is alkylated only at the y-position to give (66) in high yields. 

Tetronic acid has been prepared in three steps from enamines derived from 4-chIoroacetoacetate, and 2,4-dialkyltetronic acids are produced in good yield by ozonolysis of 2,6-dialkyl-3,5-dihydroxy-l,4-benzoquinones. ° The vinyl-lithium (72) can be obtained from the parent enamine by reaction with Bu Li. ° Subsequent condensation with alkaryl ketones and cyclization leads to the tetronic acid derivatives (73) in 20—50% yield. 

Tetronic acid derivs. Components isol. from the cultures of the Actinomycete strain DSM 7357. Inhibitors of HIV-1 protease. Isol. as Na salts. 

Tetronic acid deriv. Prod, by Streptomyces sclerotialus. Gastric ATP-ase inhibitor. 

Six antibiotically active tetronic acid derivatives have been isolated from... 

The Mannich reaction and its variants have been reviewed, mainly focussing on asymmetric catalysis thereof. Catalytic, enantioselective, vinylogous Mannich reactions have also been reviewed, covering both direct and silyl dienolate methods. Another review surveys Mannich-type reactions of nitrones, oximes, and hydrazones. A pyrrolidine-thiourea-tertiary amine catalyses asymmetric Mannich reaction of N-Boc-imines (e.g. Ph-Ch=N-Boc) with ethyl-4-chloro-3-oxobutanoate to give highly functionalized product (16). Addition of triethylamine leads to one-pot intramolecular cyclization to give an 0-ethyl tetronic acid derivative (17). ... 

With the advent of powerful spectroscopic and A -ray techniques, carrying out a total synthesis merely to prove the structure of a natural product has lost much of its earlier glamour. However, the discipline is still valid, as reflected in the recently described synthesis of the structures (209a) and (209b), which had been widely accepted for the natural tetronic acid derivatives gregatin B and aspertetronin A, respectively. Inspection and comparison of the spectral data that were obtained for synthetic (209a) and (209b) with those reported for the natural products showed that the natural products did not have structures... 

TETRONIC ACID DERIVATIVE 67 or 2-(3 methylbutanoyl)-4-(3-methyl-2-bute-nyl)- tetronic acid. 

Oxidation of hop bitter acids may be accompanied by opening of the ring skeleton, whereby complex, multifunctional, acyclic compounds are formed as intermediates, leading finally to stable oxidation products. Proof for such a process is provided by the isolation and the identification of a tetronic acid derivative. 

The tetronic acid derivative is obtained as by-product upon boiling of humulone in an aqueous buffer pH 5.4. It is isolated as the band with K 0.35 by CCD distribution in the two-phase system iso-octane buffer pH 3.95 after 800 transfers. The light-yellow oil with molecular formula C. 4H2o04 and a pKy( value of 2.8 absorbs in the UV region... 

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