1.3- Dioxane-4,6-diones alcoholysis

Ethyl 3-oxoalkanoates when not commercially available can be prepared by the acylation of tert-butyl ethyl malonate with an appropriate acid chloride by way of the magnesium enolate derivative. Hydrolysis and decarboxylation in acid solution yields the desired 3-oxo esters [59]. 3-Keto esters can also be prepared in excellent yields either from 2-alkanone by condensation with ethyl chloroformate by means of lithium diisopropylamide (LDA) [60] or from ethyl hydrogen malonate and alkanoyl chloride usingbutyllithium [61]. Alternatively P-keto esters have also been prepared by the alcoholysis of 5-acylated Mel-drum s acid (2,2-dimethyl-l,3-dioxane-4,6-dione). The latter are prepared in almost quantitative yield by the condensation of Meldrum s acid either with an appropriate fatty acid in the presence of DCCI and DMAP [62] or with an acid chloride in the presence of pyridine [62] (Scheme 7). 

In order to mimic the C-terminal end of the parent peptide (37), we introduced a 2-isobutyl malonyl derivative in place of the original C-terminal leucine residue. The malonyl residue was incorporated in the peptide chain as a tert-hutyl monoester (40) obtained by alcoholysis of the 2,2-dimethyl-5-isobutyl-l,3-dioxane-4,6-dione (39) (Fig. 5). 

Figure 5 The 2-isobutyl malonyl derivative 40 used in the synthesis of 38 was prepared by alcoholysis of 5-isobutyl-l,3-dioxane-4,6-dione 39 [135].

Malonic acid monoesters from l,3-dioxane-4,6-diones Asym. alcoholysis... 

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See also in sourсe #XX -- [ , ]

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