Tetronic acids synthesis

Greenhill and Tomassini158 introduced an exceptionally simple tetronic acid synthesis from methyl but-2-yndioate (Scheme 39). It contains features... 

Lactones General Synthesis Synthesis of P-Lactones Synthesis of Butyrolactones Synthesis of Butenolides Synthesis of Phthalides Synthesis of Tetronic Acids Synthesis of a-Methylenebutyrolactones Synthesis of Valerolactones... 

Chemoselective C-alkylation of the highly acidic and enolic triacetic acid lactone 104 (pAl, = 4.94) and tetronic acid (pA, = 3.76) is possible by use of DBU[68]. No 0-alkylation takes place. The same compound 105 is obtained by the regioslective allylation of copper-protected methyl 3,5-dioxohexano-ate[69]. It is known that base-catalyzed alkylation of nitro compounds affords 0-alkylation products, and the smooth Pd-catalyzed C-allylation of nitroalkanes[38.39], nitroacetate[70], and phenylstilfonylnitromethane[71] is possible. Chemoselective C-allylation of nitroethane (106) or the nitroacetate 107 has been applied to the synthesis of the skeleton of the ergoline alkaloid 108[70]. 

Butenolide, 2-hydroxy — see Isotetronic acids Butenolide, 3-hydroxy — see Tetronic acids But-2-enolide, 4-alkylidene-synthesis, 4, 697 Butenolides H NMR, 4, 578 mass spectrometry, 4, 585 structure, 4, 551 synthesis, 1, 416 trimethylsilylation... 

The synthesis of a selenonium ylide with a tetronic acid anion moiety was reported (83TL75 84CPB2666). 3-Enamino-tetronie aeids have also been investigated (82SC431). 

Schemes 16-19 present the details of the enantioselective synthesis of key intermediate 9. The retrosynthetic analysis outlined in Scheme 5 identified aldoxime 32 as a potential synthetic intermediate the construction of this compound would mark the achievement of the first synthetic objective, for it would permit an evaluation of the crucial 1,3-dipolar cycloaddition reaction. As it turns out, an enantioselective synthesis of aldoxime 32 can be achieved in a straightforward manner by a route employing commercially available tetronic acid (36) and the MEM ether of allyl alcohol (74) as starting materials (see Scheme 16).

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]. 

Duffield, J.J. and Regan, A.C. (1996) Asymmetric synthesis of tetronic acids by Blaise reaction of protected optically active cyanohydrins. Tetrahedron Asymmetry, 7, 663-666. 

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. 

Clemo, N. G. Pattenden, G. Vinylic carbanions in synthesis. Novel synthesis of iso-gregatin B, iso-aspertetronin A and related O-methyl tetronic acids. Tetrahedron Lett. 1982, 23, 585-588. 

So, if the ester is enolisable, use the Me3SiCl method. If it isn t enolisable you don t need to. The a-diketones 57 were needed for the synthesis of tetronic acids. Changing the oxidation level of one ketone reveals a symmetrical acyloin 58 derived from the esters 59. 

The Claisen ester enolate reaction has proved to be extremely useful in the synthesis of a large number of natural products.3 In addition, the rearrangement has been extended to allow the preparation of useful intermediates such as a-alkoxy esters,88 329 33 336 343 a-phenylthio esters,339344-345 a- and [3-amino acids,340 346-350 a-fluoro esters,351 cycloalkenes,352353 tetronic acids,354 and dihydro-pyrans.355-357... 

The monoallylation of tetronic acid can be achieved by using it in large excess with respect to the allyl acetate (30). Node and co-workers used this method to prepare 31 as a step in the synthesis of the natural product 32 (94T8337), as shown in Scheme 8. 

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. 

Total synthesis of macrolide and ionophore antibiotics containing fragments of tetronic acid 92YZ358. 

The Brown allylboration was used in the enantioselective total synthesis of (-)-calicheamicinone 3318 (Scheme 3.1o). Thus the lactol 34, readily prepared from tetronic acid, was treated with the allylborane d35 to give 36 in a highly stereoselective manner (95% ee, > 98% de). Compound 36 was converted to the aldoxime 37 by standard chemistry. Generation of the nitrile oxide with aqueous sodium hypochlorite was accompanied by spontaneous [3 + 2]-dipolar cycloaddition to afford 38 in 65% yield. 

A highly diastereoselective method for the synthesis of tetronic acids has heen developed based upon a tandem Claisen condensation/transesterification between arylacetate enolates and arylmethylene-substituted 2,2-dimethyl-l,3-dioxolan-4-ones. The versatility of this method has been demonstrated in an improved synthesis of (Z)-configured pulvinones (Equation 58) <20078118>. 

Tetronic acids. N,N -Carbonyldiimidazole (1) can serve as an equivalent of C=0 in a synthesis of tetronic acids from dianions of a-hydroxy ketones or a -diketones. ... 

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) . ... 

Sodeoka M, Sampe R, Kojima S, Baba Y, Usui T, Ueda K, Osada H. Synthesis of a tetronic acid library focused on inhibitors of tyrosine and dual-specificity protein phosphatases and its evaluation regarding VHR and Cdc25B inhibition. J. Med. Chem. 2001 44 3216-3222. 

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