Tetronic acid, reaction with synthesis

Partially hydrogenated quinoline cores are also present in some important bioactive compounds. For example, the 4-aza-analogs of Podophyllotoxin, a plant lignan that inhibits microtubule assembly, revealed to be more potent and less toxic anticancer agents. In 2006, Ji s group reported a green multicomponent approach to a new series of these derivatives, consisting of the reaction of either tetronic acid or 1,3-indanedione with various aldehydes and substituted anilines in water under microwave irradiation conditions (Scheme 26) [107]. For this efficient and eco-friendly transformation, the authors proposed a mechanism quite similar to the one that was postulated for the synthesis of tetrahydroquinolines in the precedent section. 

The synthesis of medicinally relevant 4-substituted 2(5//)-furanones has been achieved by a coupling reaction of the triflate derived from p-tetronic acid with alkyl-and cyclopropylboronic acids (Scheme 10.8).22 This reaction was mediated by bis(acetonitrile)dichloropalladium and silver oxide. Interestingly, optically active cyclopropyl boronic acids were not racemized during this coupling reaction. 

Tu et al. have reported the synthesis of 4-aza-podoplyllotoxin via a three-component reaction of an aldehyde, aniline and cyclic diones in H2O under MWl. Use of tetronic acid as the cyclic diketone provided the 4-aza-podophyllotoxin derivatives (76) (Scheme 6.30). The reaction proceeded via the attack of Schiff s base, formed through the condensation between aldehyde and aniline, on tetronic acid resulting into an intermediate which underwent intramolecular cyclization and dehydration to yield the product. The scope of the strategy was enhanced by replacing tetronic acid with 1,3-indanedione to generate indenoquinoline derivatives (77) [69]. 

In 1985, Campbell et al. [58] employed a Dieckmann condensation strategy to the synthesis of pulvinones. By this route, Campbell prepared tetronic acid 61 that can be either transformed to phosphorane 62 and utilized in Wittig reactions or condensed with arylaldehydes that can afford pulvinones after dehydration. The first route led Steglich s group in 2000 to the total synthesis of aurantricholides A (65) and B (66), two minor pigments of toadstool Tricholoma aurantium [59], whereas... 

Tetronomycin (102), a structurally challenging 3-acyltetronic acid ionophore antibiotic, was isolated from a Streptomyces strain in the early 1980s [71]. The only total synthesis reported so far was accomplished in 1992 by Yoshii and coworkers (Scheme 1.14) [72]. By using as chiral building blocks the ethoxyethyl ether 98 and L-rhamnal diacetate 99, Yoshii reached aldehyde 100, a suitable precursor for the installation of the tetronic moiety. This was achieved by a reaction with the lithium anion of methyl tetronate 101 at —100°C that led to the target after pyridinium chlorochromate (PCC) oxidation and careful deprotection. 

Paleta O, Volkov A, Hetllejs J (2000) Fluorinated butanolides and butenohdes, part 5. Synthesis and nucleophilic reactions of 3-chloro-2-fluoro-2-buten-4-olide as tetronic acid analogue. Conjugate addition of hard nucleophiles and vinylic halogen displacement with soft phosphorus nucleophiles. J Fluor Chem 102 147—157... 

Synthesis of Tetronic Acids. —Lithiation of methyl p-methoxyacrylate and reaction with the dienone (198) leads to the tetronate (199), in one step. Further lithiation of (199), followed by acylation, is then shown to produce the enol ether isomer (200) of natural aspertetronin A (Scheme 108). In similar studies. 

Regio-directed metallations have been used this year to good effect in the synthesis of tetronic acids. Two papers have appeared on the lithiation of the acrylates (8) at the p-position to yield tetronic acids (9 X = H) after reaction with aldehydes, ketones, and esters. " The tetronic acids (9 X = H) can then be lithiated to give (9 X = Li) and further reacted to provide the substituted tetronic acids (9 X = E). " " In this way isomers of the naturally occurring gregatins and aspertetronins have been synthesized. "... 

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