Dane-anhydride

The so-called Dane-anhydride route for the synthesis of semi-synthetic / -lactam antibiotics can be used practically for aU members of this class of compounds, and may be exemplified here for amoxicillin. (D)-4-Hydroxyphenylglycine is treated first with the potassium salt of ethyl acetoacetate and then with pivaloyl chloride. This results in the Dane-anhydride, which may easily be coupled with 6-aminopeniciUanic acid. 

A domino reaction,in this case consisting of an inter- and an intramolecular Diels-Alder reaction, is a key step in the synthesis of the hydrocarbon pago-dane 30, reported by Prinzbach et al When the bis-diQnQ 27 is treated with maleic anhydride 4, an initial intermolecular reaction leads to the intermediate product 28, which cannot be isolated, but rather reacts intramolecularly to give the pagodane precursor 29 ... 

On activation of Dane s salt by an acyl halide to give a mixed anhydride, N-acylation is prevented by the enaminone moiety. The product of cyclocondensation can be hydrolysed, losing the enaminone group to yield a free aminoazetinone. Such /Mactam derivatives are of great interest due to the structural analogy to aminopenicillins and cephalosporins. 

Oxidation of the alcohol 374, obtained by base-hydrolysis of the acetate 311 (3.4.3.), with Jones-reagent yielded the ketone 375. Unsubstituted 2,8-dioxa-homotwistbren-dane 377) was prepared by converting the ketone 375 to its thioketal 376, which on reductive desulfuration with raney-nickel gave 377. The enolacetate 378 was available by reaction of the ketone 375 with triphenylethylUthium as base followed by addition of acetic anhydride. Under acidic conditions only decomposition could be observed and with pyridine as base no reaction took place. 

The INOC reaction also plays a crucial role in the synthesis of the trans-hydrindane derivative 322, a potential intermediate for the synthesis of the C2-symmetric pentacychc alkaloid papuamine 319 (1997CC495). Nitroal-kene 321 was prepared from racemic anhydride 320 in a few steps. Nitrile oxide formation was then carried out in situ by the reaction of 321 with PhNCO which resulted in cyclization to afford the racemic irares-hydrin-dane 322 (Scheme 58). 

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