Zearalenone synthesis

The intramolecular coupling of organostannanes is applied to macrolide synthesis. In the zearalenone synthesis, no cyclization was observed between arylstannane and alkenyl iodide. However, intramolecular coupling take.s place between the alkenylstannane and aryl iodide in 706. A similar cyclization is possible by the reaction of the alkenylstannane 707 with enol triflate[579]. The coupling was applied to the preparation of the bicyclic 1,3-diene system 708[580]. 

Zearalenone growth promotant veterinary use, 1, 219 ( )-Zearalenone synthesis, 1, 479 Zeatin... 

Scheme 52. Zearalenone synthesis via allylic radical cyclization...

An intramolecular variant of the Stille coupling is suitable for the construction of macrocycles. An example is the ring-closing step to form a 14-membered lactone ring 8 in a synthesis of zearalenone as reported by Stille et al. ... 

An intramolecular palladium(o)-catalyzed cross-coupling of an aryl iodide with a trans vinylstannane is the penultimate maneuver in the Stille-Hegedus total synthesis of (S)-zearalenone (142) (see Scheme 38).59 In the event, exposure of compound 140 to Pd(PPh3)4 catalyst on a 20% cross-linked polystyrene support in refluxing toluene brings about the desired macrocyclization, affording the 14-membered macrolide 141 in 54% yield. Acid-induced hydrolysis of the two methoxyethoxymethyl (MEM) ethers completes the total synthesis of 142. 

Grignard reaction and similar transformations allow C-C bond formation without a palladium catalyst. Grignard reagents and organolithium compounds are very versatile carbanion sources used in the synthesis of acyclic, heterocychc and carbo-cychc compounds. The esters, ketones and aldehydes are more stable when the reaction takes place on solid supports than in the hquid-phase, because this immo-bihzed components are not so sensitive towards water or oxygen. In the total synthesis of (S)-zearalenone (155) on solid supports the Grignard reaction is one of the key steps (Scheme 3.16) [120]. 

Scheme 3.16 Grignard key step for the synthesis of (S)-zearalenone (155) by Nicolaou et al. [120].

Reaction (7.61) shows an example of macrocyclization which represents the key step in the total synthesis of the macrolide (—)-zearalenone [71]. 

In the total synthesis of zearalenone (451), the ester 450 was prepared by the carbonylation of the crowded aryl iodide 448. The alkyl iodide moiety in the alcohol molecule 449 is not attacked[306]. Methyl trifluoromethacrylate (453) was prepared by the carbonylation of 3,3,3-trifluoro-2-bromopropylcne (452). The carbonylation in the presence of alkylurea affords 454, which is converted into the trifluoromethyluracii 455[307],... 

This total synthesis is the first of three preparations of macrocycles that will be described (epothilone A, zearalenone, and muscone). All feature cycli-zation/release strategies that involve carbon-carbon bond formation.18 These efforts illustrate how the research on supported syntheses of highly complex structures has inspired the use of creative linker strategies for attachment to a solid phase. 

Coupling of aryl halides with alkenyl stannanes promoted through palladium metal catalysis, otherwise known as the Stille coupling, has many applications,22 including solid-phase variants (see Chapter 2).3-5 One of these is featured in Nicolaou and co-workers solid-phase synthesis of (5)-zearalenone wherein a resin-bound alkenylstannane undergoes a Stille cycli-... 

The synthesis of (S)-zearalenone began with creation of the chlo-rodibutylstannyl polystyrene resin 32, which ultimately would serve as a Stille coupling partner. Oxidation of chloromethyl polystyrene resin fol-... 

Nicolaou, K. C. Winssinger, N. Pastor, J. Murphy, F. Solid-Phase Synthesis of Macrocyclic Systems by a Cyclorelease Strategy Application of the Stille Coupling to a Synthesis of (.S )-Zearalenone, Angew. Chem. Int. Ed. Eng. 1998, 37, 2534. 

If the halide and the hydroxy group are present in the same molecule, reaction (107) leads to the synthesis of lactones.484 With complex (102) as catalyst a series of butenolides were prepared in good yields from vinyl iodides (equation 110). Four- and six-membered ring lactones and a-methylene lactones were prepared. 5,486 The mechanism proposed was analogous to that of Scheme 37. This cyclization has been used in the synthesis of the natural product zearalenone.487 PdCl2 was the catalyst. 

Even the sterically hindered 2,6-disubstituted aryl iodide 443 is carbonylated smoothly to give 445. Alkyl iodide present in the alcoholic component 444 remains intact under the carbonylation conditions. This carbonylation reaction is a key reaction in the synthesis of zearalenone (446) [216]. Optimal conditions for technical synthesis of the anthranilic acid derivative 448 from bromide 447 has been studied, and it has been found that A-acetyl protection of 447, which has a chelating effect, is important [217]. Cheaply available chlorides are rather inert [13]. The carbonylation of chloride 449 in the presence of DBU and Nal gives the amide 450 [218],... 

Scheme 6.1.21. A cleavage Stille strategy using a stannane linker for the synthesis of zearalenone 97.

Cyano-stabilized anions have been internally alkylated to generate 10-581, 14-582 and 16-membered583-586 rings. The ring-closure step in a synthesis of zearalenone has been performed in this way (equation 89)582. 

In the synthesis of zearalenone, a key reaction is the formation of the aromatic ester moiety. This has been carried out in 70% yield by the ester-forming carbonylation process illustrated in equation 159906. A similar reaction has been used for the synthesis of the natural product curvulin907. 

The mixed trifluoroacetic anhydride method played an important role in the first synthesis of the 14-membered macrolide zearalenone (70) by Taub et al. [42]. Hydroxy acid 68 was treated with trifluoroacetic anhydride (TFAA) and lactone 69 was obtained in 15% yield (Scheme 22),... 

In the synthesis of (S)-zearalenone and of a chiral spiroac-etal, (2S,6/ )-2-methyl-l,7-dioxaspiro[5.6]dodecane, the starting product was a functionalized 3-keto sulfoxide resulting from the reaction of glutaric anhydride with lithiated (+)-(7 )-methyl p-tolyl sulfoxide (eq 6). 

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