Pyrrolizidine dilactones

Membered pyrrolizidine dilactones have been synthesized by treating a trimethylsilylethyl ester with TBAF in MeCN to form an anion, which then undergoes cyclization by displacement of the mesylate. 

This method of cyclization has been used successfully for synthesis of four 11-membered dilactone pyrrolizidine alkaloids,2 but it does not appear to be useful for cyclization to simple macrolides. 

Integeninecic acid (36), which occurs as the dilactone in die pyrrolizidine alkaloid integeirimine (33 Scheme 9), was obtained from ketone (34). The observed regioselectivity in die oxidation leading to (35) presumably results from steiic and dipolar effects. ... 

A series of 11-membered dilactones [(4) - (8)] have been prepared in 50 - 75% yield from (+)-retronecine (1) and the corresponding substituted glutaric anhydride (cf. Vol. 11, p. 49). These pyrrolizidine alkaloid analogues exhibited a range of A6 (H-9) values shown on the formulae. These values probably reflect the different conformations in the diacid portions. The... 

Some alkaloids have macropolylide skeletons in their structures in particular, many pyrrolizidine alkaloids have structures with each pyrrolizidine skeleton fused to a macrocyclic dilactone or trilactone [169]. Crotalarine (Fig. 25,141) is a 10-membered ring macrodiolide isolated from Crotalaria burhia [170]. Seneci-phylline (142) is a 12-membered ring macrodiolide isolated from Senecio spp. 

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