4-hydroxy-2-isoxazolines, synthesis from

A great deal of the interest in isoxazolines stems from their use in the synthesis of acyclic compounds (19). The approach to (3-hydroxy carbonyl compounds via... 

Talaromycin B is a spiro-acetal produced by the fungus Talaromyces stipitatus, the toxicity of which may be due to its ability to block outward potassium fluxes. In an elegant synthesis, the requisite open-chain polyol with hydroxy groups in the y-and y -positions was assembled from nitrile oxide and olefin building blocks 50 and 51, both of which carry a f>w(hydroxyethyl) moiety protected as a cyclohexanone acetal (284). Hydrogenolysis of the N O bond of isoxazoline 52 using Raney nickel, followed by treatment with aqueous acid, gave the spiroketal 53, which was further transformed into racemic talaromycin B (54) (Scheme 6.54) (284). 

Isoxazolines can be transformed into a,p-enones by several methods from the initial aldol product. This strategy was applied by Barco et al. (285) toward the synthesis of ( )-pyrenophorin (98), a macrocychc fow(enone-lactone) with antifungal properties. The hydroxy group was introduced from the nitrile oxide component (95), while the carboxy function was derived from the acrylate dipo-larophile. Thus, cycloaddition of the optically active nitropentyl acetate 94 to methyl acrylate 95 afforded isoxazoline 96 as a mixture of optically active diastereomers. Reductive hydrolysis using Raney nickel/acetic acid gave p-hydro-xyketone (97), which was subsequently utilized for the synthesis of (—)-pyreno-phorin (98) (Scheme 6.63) (285). 

An early example of this type of transformation was described in 1964 by Drehfahl and Horhold (310). These authors prepared racemic 4-hydroxyproline, albeit with low diastereoselectivity for the isoxazoline reduction step [Scheme 6.75, (1)] (310). Much higher selectivity was achieved using 5-halomethylisoxazolines bearing a 3-(l-oxyalkyl) side chain, which was introduced from the nitrile oxide portion. The examples presented in Scheme 6.75 outline the synthesis of 4-hydroxy-pyrrolidines, which contain a dioxyethyl or trioxypropyl side chain. Both of these substrates were converted into the corresponding imino acids of 4-hydroxyproline (23,225,234) and 4, 1 -dihydroxyhomoproline, respectively (23,207,225) (Eq. 2, 3). The latter compound is part of an N-Val dipeptide structure, that was mistakenly proposed for the antibiotic Tii 1718B (311,312). 

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