Loline synthesis

An intermediate 5-hydroxy-5,6-dihydro-2/7-pyrrolo[l,2- ][l,2]oxazin-7(4a//)-one 142 has been described in the total synthesis of (—)-loline, a pyrrolizidine alkaloid extracted from rye grass Lolium cuneatum. The key step of the synthesis was an intramolecular cycloaddition of acylnitrosodienes (obtained by in situ oxidation of the corresponding hydroxamic acids 143). This reaction generated predominantly the rro/o-stereoisomer that was further cleaved at the N-O bond with Na(Hg) and further elaborated in several steps to reach the target compound (Scheme 19) <2001J(P 1)1831 >. 

Details of the synthesis of the ring system of the loline alkaloids [as in loline (33)] have now been provided ( f. Vol. 10, p. 50). The authors speculate on the close biogenetic... 

This synthetic strategy has been extended by the same authors to the synthesis of the ring system of the loline alkaloids. Seven simple loline alkaloids [e.g. loline (9)] and one dimeric species have been identified (see these Reports, Vol. 8, Ch. 3). The ketone (10) was converted into the amine (11) in analogous fashion to the formation of (7) from cyclohept-4-enone (see Scheme 3). Treatment of the amine (11) with bromine led to transannular cyclization and formation of the 3-aza-9-oxabrendane system (13) in good yield (85%), as shown in Scheme 4. The... 

Conversion of loline (3) to norloline (4) required a rapid means to distinguish these two compounds (22). Detection of (3) and (4) on tic plates was accomplished by spraying with 2-hydroxy-l-naphthaldehyde this reagent has been used as an amino function protection reagent in peptide synthesis... 

Total synthesis of loline (3) and norloline (4) was accomplished using a nitrone-based strategy (47). Methyl 2-hydroxy-7,7-dimethoxy-8-pyrrolizidine-1-carboxylate (20) was prepared from nitrone (21) and methyl 4-hydroxycrotonate (22). Epimerization at C(l) was accomplished with sodium methoxide in methanol to yield 23. Reduction of 23 with LiAlH4 produced... 

Chapter 4 summarizes available knowledge about the loline-type pyrrolizi-dine alkaloids. These alkaloids have been reported from only a few genera of grasses (Poaceae). Their occurrence in grasses is closely associated with the presence of endophytic fungi. The chapter treats isolation, characterization, synthesis and the biological activities of these alkaloids. 

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