1250330-04-1Relevant articles and documents
Thione esters as substrates for the stereoselective alkylation of model compounds of nonactic acids
Loiseau, Francois,Kholod, Inga,Neier, Reinhard
experimental part, p. 4642 - 4661 (2010/10/19)
The naturally occurring macrotetrolide antibiotic nonactin is used in ammonium ion selective electrodes. To increase the lifetime of nonactin in the semipermeable membrane of these sensors we have developed methods for the introduction of hydrophobic side-chains. Simple model compounds for nonactic acid such as 5 and 7 were synthesised. Maintaining the cis arrangement of the substituents in the 2,5-disubstituted tetrahydrofurans proved to be difficult. Three different routes were studied. The enolates obtained by treatment with NaHMDS or KHMDS could be alkylated with benzyl or allyl iodide as electrophiles. Under these conditions a cis/trans isomerisation of the substituents on the tetrahydrofuran ring occurred. A multistep methodology was developed as a syn- thetic alternative. The sequence consisted of a selective retro-Michael reaction, a 5-exo-tet iodocyclisation and a radical substitution. The products obtained by the two methodologies could be correlated, and thereby a tentative assignment of the relative configurations could be achieved. In the third route the thione ester 18 was deprotonated with tBuOK. At temperatures below -78°C, the enolate maintained the cis configuration of the substituents at the tetrahydrofuran ring. The alkylated product 12 could be isolated with a satisfactory cis/trans ratio of 85:15. The model compound 12 could be successfully transformed into more hydrophobic derivatives by using either the Heck coupling or the cross-coupling metathesis transformation.
