Synthesis, structural characterization and biological activity of two diastereomeric JA-Ile macrolactonesElectronic supplementary information (ESI) available: Fig. S1, S2 and a copy of NMR spectra of important compounds. CCDC 1004515 and 1004516. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ob00362h

Jasmonates are phytohormones involved in a wide range of plant processes, including growth, development, senescence, and defense. Jasmonoyl- l -isoleucine (JA-Ile, 2 ), an amino acid conjugate of jasmonic acid (JA, 1 ), has been identified as a bioactive endogenous jasmonate. However, JA-Ile ( 2 ) analogues trigger different responses in the plant. ω-Hydroxylation of the pentenyl side chain leads to the inactive 12-OH-JA-Ile ( 3 ) acting as a "stop" signal. On the other hand, a lactone derivative of 12-OH-JA ( 5 ) (jasmine ketolactone, JKL) occurs in nature, although with no known biological function. Inspired by the chemical structure of JKL ( 6 ) and in order to further explore the potential biological activities of 12-modified JA-Ile derivatives, we synthesized two macrolactones (JA-Ile-lactones ( 4a ) and ( 4b )) derived from 12-OH-JA-Ile ( 3 ). The biological activity of ( 4a ) and ( 4b ) was tested for their ability to elicit nicotine production, a well-known jasmonate dependent secondary metabolite. Both macrolactones showed strong biological activity, inducing nicotine accumulation to a similar extent as methyl jasmonate does in Nicotiana attenuata leaves. Surprisingly, the highest nicotine contents were found in plants treated with the JA-Ile-lactone ( 4b ), which has (3 S ,7 S ) configuration at the cyclopentanone not known from natural jasmonates. Macrolactone ( 4a ) is a valuable standard to explore for its occurrence in nature. The synthesis and biological activity of two diastereomeric macrolactones derived from the partially inactive jasmonate 12-OH-JA-Ile are discussed. Both diastereoisomers induce nicotine production similar to methyl jasmonate in Nicotiana attenuata plants.