Retusanecic acids

Synthetic work by another Japanese group has resulted in the synthesis of a-and j -retusanecic acids, and retusaminic acid. The retusanecic acids are obtained by the alkaline hydrolysis of retusine (44), and have been shown to be epimeric 4-hydroxy-2,3,4-trimethylglutaric acid lactones. Since in acidic solution the equilibrium favours the j3-acid, it is formulated as (45), in which the C-2 methyl group is trans with respect to the C-3 methyl group a-retusanecic acid is... 

These epimeric acids are formed on alkaline hydrolysis of retusine (Table 3K). They have been synthesised by Kiyooka and Hase 161) as shown in Scheme 17. The cyanolactone (56) was prepared by HCN addition to the ketone (55). The relative stereochemistry of the corresponding ethyl ester (57) was confirmed by independent synthesis from trans-o tmng of the epoxide (58). Methylation of (57), followed by hydrolysis and decarboxylation gave a mixture of the p-(59) and a-(60) retusanecic acids, in which the p-form predominated. 

This acid is derived from retusamine (Table3Pi), and has been synthesised by Kiyooka etal. 162) as shown in Scheme 18. The starting material (55) was the same as that used in the synthesis of a- and ji-retusanecic acids cf. Scheme 17), and a similar strategy was employed, except that ethylation of the starting material (55) preceded stereospecific cyanohydrin formation and cyclisation to give lactone (66). The absolute configuration of the resolved lactone acid, which was identical with retusaminic acid (67), was already known from the X-ray structure analysis of retusamine carried out by Wunderlich 319). 

Kiyooka, S., and T. Hase Pyrrolizidine Alkaloids The Synthesis and Stereochemistry of a- and p-Retusanecic Acids. Bull. Chem. Soc. (Japan) 46, 3609 (1973). 

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