Total Synthesis of Phomazarin

Abstract

A concise total synthesis of phomazarin (1) is detailed enlisting a heterocyclic azadiene inverse electron demand Diels−Alder reaction (1,2,4-triazine → pyridine) for preparation of the fully substituted and appropriately functionalized pyridine C-ring. Thus, [4 + 2] cycloaddition (85%) of triethyl 1,2,4-triazine-3,5,6-tricarboxylate (2) with trimethoxyethylene (3) followed by conversion of the cycloadduct 11 to the cyclic anhydride 13 provided the phomazarin C-ring with the three carboxylates suitably differentiated. Linkage of the A- and C-rings through selective nucleophilic addition of the aryllithium reagent 9 to the least hindered anhydride carbonyl of 13 followed by Friedel−Crafts closure of the B-ring provided the fully functionalized phomazarin skeleton. The successful structural correlation of synthetic 1 with natural material and its derivatives confirmed the latest structural assignment for the natural product.

Six‐Membered Heterocycles: Triazines, Tetrazines and Other Polyaza Systems

“…Some reviews on inter-and intramolecular Diels-Alder reactions have appeared [30,120,360,361]. 1,2,4-Triazines participate as electron-poor dienes in inverse type Diels-Alder reactions with electron-rich dienophiles such as dienes [120,244], enamines [362][363][364][365][366][367][368][369][370][371][372] or methoxyethylene [373] to yield pyridine derivatives 213 (Scheme 20.64). Cycloaddition of 1,2,4-triazines with ynamines to yield pyrimidines 214 [374][375][376] has also been studied.…”

Two new chelidamate complexes with the 4-methoxypyridine: A combined theoretical and experimental study

“…4-Hydroxypyridine-2,6-dicarboxylic acid or chelidamic acid (H 2 chel), is commonly used organic chemistry, biochemistry, coordinate chemistry, medical chemistry and even in HIV investigation [1][2][3][4][5][6][7]. A great deal of interest has been devoted to syntheses of chelidamic acid and its derivatives due to their various coordination modes and the potential applications in luminescent probe, radical adsorption and ferromagnetic interaction [8,9].…”

Synthesis, crystal structure and optical properties of a novel 1D coordination polymer [Zn3(C7H2NO5)2·8(H2O)]n

“…Chelidamic acid (2,6-dicarboxy-4-hydroxypyridine) (hereafter HChel) is a polydentate ligand which has been of great attraction due to its use in many areas of science, such as coordinate chemistry, biochemistry, organic chemistry, medical chemistry and even in HIV investigation [11][12][13][14][15]. A large number of metal complexes containing chelidamic acid ligands have been reported, which played a significant role in molecular design and the extension of the chemistry of chelidamic acid [16][17][18][19][20].…”