Tricarballylic esters

Fig. 8. Chemical structures of different classes of fumomsins. The R residue is 3-hydroxypyridmium in fumonisins P1-P3 while the others are tricarballyl esters. 

Based on the paradigm of NRPS-catalyzed reactions, we proposed a mechanism for the biosynthesis of the tricarballylic esters of fumonisins (Figure 5). The first step is the ATP-dependent activation of a tricarboxylate substrate by FumlOp to form an acyl-AMP, which is subsequently transferred to the PCP domain of Fuml4p. The exact substrate for FumlOp is not known, but is likely to be an intermediate of the tricaroxylatic acid cycle 17). The data obtained from the FUM7 deletion mutant suggested that the substrate of FumlOp could be a... 

V. Miller applied this method to a number of other mixtures. Thus upon the electrolysis of a mixture of acetic ester with tricarballylic ester, one third... 

The addition of active methylene compounds (ethyl malonate, ethyl aceto-acetate, ethyl plienylacetate, nitromethane, acrylonitrile, etc.) to the ap-double bond of a conjugated unsaturated ketone, ester or nitrile in the presence of a basic cataljst (s ium ethoxide, piperidine, diethylamiue, etc.) is known as the Michael reaction or Michael addition. The reaction may be illustrated by the addition of ethyl malonate to ethyl fumarate in the presence of sodium ethoxide hydrolysis and decarboxylation of the addendum (ethyl propane-1 1 2 3-tetracarboxylate) yields tricarballylic acid ... 

C domains can display functions that deviate from typical amide bond formation. Several C domains are postulated to act as ester synthases, catalyzing ester formation instead of amide formation. NRPS modules containing C domains that display this activity are present in the biosynthetic pathways for the kutznerides, cryptophycins, " cereulide, valinomycin, hectochlorin, and beauvericin. Each of these C domains likely utilizes a PCP-bound a-hydroxyl acceptor in the condensation reaction. Another NRPS C domain that catalyzes ester bond formation is involved in the biosynthesis of the polyketide-derived mycotoxins known as the fiimonisins. Du and coworkers have shown that a recombinant PCP-C didomain of an NRPS involved in the biosynthetic pathway of the fnmonisins can catalyze ester bond formation between hydroxyfumonisins and the A-acetylcysteamine thioester of tricarballylic acid, even though PCP-bound tricarballylic acid is not... 

Another example is camphoronic acid (aaj3-tri-methyl-tricarballylic acid), an oxidation product of camphoric acid, which can be synthesised from a-brom-isobutyric ester and acetoacetic ester.6... 

Dihydroshikimic acid methyl ester Tricarballylic acid 1,5-dialdehyde methyl ester 56... 

Tricarballylic acid, 1,2,3-propanetricarboxyIic acid, is produced by the reduction of aconitic acid by catalytic methods,107-111 electrolyti-cally,112-114 or by sodium amalgam.50-115 Sulfotricarballylic acid (VII), its salts, and its esters have become of interest recently due to their... 

Tricarballylic Acid.—The potassium salt of the diester of this acid was subjected by von Miller 2 to the Brown-Walker reaction, but without success. The ester-acid was in part regenerated. When potassium acetate, however, was added to the anode solution the expected reaction occurred ethylsuc-cinic ester was produced ... 

The peculiar fact that the di-esters of tricarballylic acid, when electrolyzed by themselves, do not afford the expected synthetical reaction, while the electrolysis of a mixture of the acid with potassium acetate gives these synthetic products, was made use of by von Miller with several aromatic acids which had previously proven unsuitable for synthesis when used alone (see these). 

Fumonisins are a group of toxins produced primarily by Fusarium verticil-lioides (formerly called F moniliforme), Eprolifemtum and other related species which readily colonize corn all over the world [120-124]. Nine structurally related fumonisins including Bj, B2, B3, B4, A, and A2, have been described (fig. 8). Chemically, fiimonisin Bj is a derivative (diester) of propane-1,2,3-tricarboxylic acid of 2-amino-12,16-dimethyl-3,5,10,14,15-pentahydroxy-icosane [121-130]. The other fumonisins lack the tricarballylic acid or other ester groups [121, 131, 132]. Fumonisins are chemically similar in structure to toxins (AAL) produced by Altemaria altemata [133]. Production of fumonisins hy Altermria has also been reported [134,135], and some fumonisin-producing Fusaria have been knovm to produce AAL toxins [136]. 

SYNS ATEC CITRIC ACID, ACETYL TRIETHYL ESTER CITROFLEX A 2 1,2,3-PROPANE-TRICARBOXYLIC ACID, 2-(ACETYLOXY)-, TRIETHYL ESTER (9CI) D TRICARBALLYLIC ACID, P-ACETOXY-TRIBLnrYL ESTER TRIETHYL ACETYLCITRATE TRIETHYL CITRATE, ACETATE TRIETHYLESTER KYSELINY ACETYLCITRONOVE... 

CAS 77-89-4 EINECS/ELINCS 201-066-5 Synonyms 2-(Acetyloxy)-1,2,3-propanetricarboxylic acid, triethyl ester ATEC Tricarballylic acid-P-acetoxytributyl ester Triethyl acetylcitrate Triethyl o-acetylcitrate Classificalion Aliphatic ester Empkical ChHjjO,... 

Acetyl triethyl citrate CAS 77-89-4 EINECS/ELINCS 201-066-5 Synonyms 2-(Acetyloxy)-1,2,3-propanetricarboxylic acid, triethyl ester ATEC Tricarballylic acid-P-acetoxytributyl ester Triethyl acetylcitrate Triethyl o-acetylcitrate Classification Aliphatic ester Empirical C14H22O8 Formula CH3COOC3H4(COOC2H5)3 Properties Colorless liq. odorless si. sol. in water m.w. 318.36 dens. 1.135 (25 C) m.p. -50 C flash pt. 187 C... 

Tricarballylic acid-P-acetoxytributyl ester. See Acetyl triethyl citrate... 

For the final part (Scheme 5.3), the 20-carbon chain of fumonisin Bj was coupled from the Uthium acetylide derived from 273 and the Weinreb amide 279 (233). After enantioselective reduction of the alkynyl ketone 281 (234, 235), the C-10 stereochemistiy was set, followed by benzyl ether formation and acid-catalyzed acetonide removal, to provide diol 282 (236). Using tricarballylic acid dibenzyl ester, the two hydroxy groups were esterified (237) and the hydrogenation of the azide, the alkyne, and the benzylic ethers led to the target product, fumonisin Bj (249). The spectroscopic analysis matched with those of commercial fumonisin Bj and further experiments on the synthetic material showed inhibitoiy activity on sphingoUpid biosynthesis. 

Harmat NJS, Mangani S, Perrotta E, Giannotti D, Nannicini R, Altamura M (2000) Enantioselective Syntheses of Orthogonally Protected Tricarballylic Acid Esters. Tetrahedron Lett 41 1261... 

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