Tetramic acid-containing compound

Two unusual tetramic acid containing compounds ascosalipyrrolidinones A 275 and B 276 and a new natural product... 

The variety of tetramic acid-containing natural products is remarkable, the area having been reviewed recently [130]. These compounds have attracted a great deal of interest, due mainly to their biological activity as potent antibiotics, because of their antiviral and antiulcerative properties, cytotoxicity and mycotoxicity, their inhibition of tumors as well as. fungicidal action. Other members are responsible for the pigmentation of certain molds and sponges. 

A reaction by Clough et al. comes close to the direct synthesis shown in Scheme 1 (89TL7469). Here amides (62) react in a radical mechanism to 4-methylene compounds (63) that with 03/PPh3 are converted to tetramic acids (64). (See Fig. 29.) Several authors, however, prepared esters of 4-amino-3-oxo-butanoic acid, which served as precursors for intramolecular cyclization to tetramic acids (82JHC883). Koehler and Gerlach in an initial stage of a synthesis of dysidine, contained in marine sponge... 

The plasmodia of the wild type of Physarum polycephalum are bright yellow and produce an orange-red pigment that is also present in a white mutant [120]. This compound, named physarorubinic acid (64), binds calcium and other metals very well and this made acquisition of the H-NMR spectrum difficult (line broadening) unless the sample was washed with aq. EDTA solution. The structure contains a decapentaene system and signals at 5 102.4 (C-3), 172.6 (C-7), 174.5 (C-2) and 194.0 (C-4) are characteristic of C-3 acylated tetramic acid unit. 

There are many compounds in this family, which contain a polyunsaturated chain bound to the tetramic acid moiety as a 3-acyl derivative. Royles has proposed the following classification for these compounds ... 

Other types of tetramic acid derivatives are A-acyl-4-methoxy-3-pyrrolin-2-ones or 4-O-methyl ethers of A-acylated tetramic acids. The only metabolites of this type containing a dienic structure are pukeleimides A (87), G (88), B (89) and F (90). They are nontoxic compounds isolated from the marine cyanophyte Lyngbya majuscula [158], a blue-green algae. 

The major components are series of homologous trimers, tetramers, and pentamers of the three acids 44-46, along with smaller quantities of dimers, hexamers, and heptamers. Furthermore, the secretion contains several isomers of each oligomer, furnishing a combinatorial library of several hundred macro-cyclic polyamines [51, 52]. Using repeated preparative HPLC fractionation, the most abundant trimeric, tetrameric and pentameric earliest-eluting compounds were isolated. One and two-dimensional H NMR spectroscopic analyses showed that these molecules were the symmetric macrocyclic lactones 48, 49, and 50 (m, n, o, p, q=7) derived from three, four or five units, respectively, of acid 46. Moreover, using preparative HPLC and NMR methods, various amide isomers, such as 53,54, and 55 (Fig. 9) were also isolated and characterized [51,52]. 

Ascorbate oxidase is a tetramer each subunit has 552 amino acids and contains 4 copper ions, the type-I blue copper center and the adjacent trinuclear center (arranged as a type-n center and a type-in dinuclear center) separated by /S-sheets (Figure 20) °. Ascorbate is oxidized to dehydroascorbate by dioxygen however, it is not bound directly to the metal center to be oxidized, but is proposed to bind near the type-I Cu site which may facihtate electron transfer to oxygen, presumably in the tri-Cu cluster site. Since humans cannot synthesize ascorbic acid, conservation of this important compound is highly regulated. For example, the oxidized ascorbate can be transported into red blood... 

Richardeau et al. investigated thiophene adsorption from liquid solutions containing hydrocarbons over HFAU zeolites in a stirred batch system at room temperature.144 They found that the maximum number of thiophene molecules adsorbed per gram of zeolites is equal to their concentration of acidic sites and considered that the acidic sites are the adsorption sites. They further found that the presence of toluene causes a large decrease in the removal of thiophene, and when the concentration of thiophene is high (27.7 wt%), an acid-catalyzed condensation of thiophene occurs to form dimers, trimers, and tetramers, which remain trapped on the zeolite. They concluded that thiophene removal by adsorption on acidic zeolites could only be carried out from diluted solutions containing no olefinic compounds. 

Interesting calixarenes and calixarene-related compounds have been obtained in one-step reactions from 1-naphthol, from the naphthalenediol disulfonate 11, and from and the bis-phenols 13, 15, and 17. Although 2-naphthol reacts with formaldehyde to yield a simple bis-naphthol, 1-naphthol produces a mixture containing 9.6% of the symmetrical cxo-OH cyclic tetramer 10 accompanied by 5% and 16% of two other cyclic tetramers in which the naphthol residues are unsymmetrically placed in the cyclic array. When the disodium salt of 1,8-dihydroxy-3,6-naphthalenedisulfonic acid (chromotropic acid) (11) is treated with an aqueous solution of formaldehyde and the mixture is allowed either to stand at room temperature for a week or is refluxed 6 h, a high yield of the endo-OH cyclic tetramer 12 is formed. The ease with which this condensation occurs is surprising in view of the deactivating effect of the sulfonic acid groups... 

Unsubstituted furoxan (1 R1 = R2 = H) is unknown. Fulminic acid (HCNO) oligomerizes readily, but the products are mainly trimers and tetramers they are summarized in part in Section V,C, and elsewhere.369,370 Monosubstituted furoxans are labile compounds, but some have been reported (not all of them reliably). The best studied are the phenylfuroxans, on which there is an extensive literature, much of it extremely confused, since Ponzio worked on the compounds for some 20 years, over which period his views on their structures changed several times, and it was only at the end that he accepted that any contained a furoxan ring. 

In contrast to flue-cured, burley, and Maryland tobaccos, highly aromatic tobaccos such as Latakia were reported to contain significant levels of free simple phenols (1876, 1877a). As the complexity of the phenols increased, the likelihood of their presence in tobacco increased and many were found in smoke as a result of direct transfer, for example, the high molecular weight phenol, 3,4-dihydro-2,5,7,8-tetram-ethyl-2-(4,8,12-trimethyltridecyl)-l//-l-benzopyran-6-ol (a-tocopherol), first identified as a tobacco leaf component by Rowland (3347) and as a tobacco smoke component by Rodgman and Cook (3271), 6,7-dihydroxy-27/-l-benzopy-ran-6-one (esculetin) identified in tobacco and its smoke by Dieterman et al. (969). In the early 1960s, Herrmann (1625, 1626) reviewed various studies on the phenols, phenolic acids, and related compounds identified in tobacco and tobacco smoke. 

Electrospray ionization (ESI) recently developed in connection with LC/MS is superior to FAB in the soft ionizations of labile high molecular weight compounds, and has the advantage of producing predominant pseudo-molecular ions such as [M+H]+ or [M+Na]" for the ionic minute compounds. The ionization effect in ESI-MS depends on whether the solvent contains acetic acid, formic acid or trifluoroacetic acid etc. This technique with direct injection has been successfully applied to hydrolyzable tannins up to tetramers when 50% aqueous MeOH or 50% aqueous acetonitrile containing a small amount of ACONH4 was used as a solvent. In this condition, the observed molecular ion species for hydrolyzable tannins are an [M+NH4] with high sensitivity. 

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