DOI: 10.1002/chem.201203585 New Synthesis of A-Ring Aromatic Strigolactone Analogues and Their Evaluation as Plant Hormones in Pea (Pisum sativum) Victor X. Chen, [a] FranÅois-Didier Boyer,* [a] Catherine Rameau, [c] Jean-Paul Pillot, [c] Jean-Pierre Vors, [d] and Jean-Marie Beau* [a, b] Introduction Strigolactones (SLs), the most recent class of hormones identified in plants, [1] are especially studied in pea, Arabi- dopsis , petunia and rice. Formed mainly in the lower parts of the stem and roots and transported presumably to the aerial parts, [2] they suppress shoot branching [3] and are in- volved in nodule formation, [4] root architecture [5] and the stimulation of cambium activity. [6] Their production would be inversely correlated with the concentration of phosphate and nitrogen available for the plants. [7] SLs belong to a class of compounds first identified in 1966 as stimulants of the seed germination of parasitic weeds Orobanche and Striga. [8] They are produced in trace concentrations and are partly ex- creted in the rhizosphere. These molecules, recently identi- fied as stimulants for spore germination and hyphal prolifer- ation of arbuscular mycorrhizal fungi (AMF), [9] were also found to have an effect on phytopathogenic fungi. [10] In these AMF symbioses, plants receive water and mineral nu- trients from their fungal partners, hence promoting optimal plant growth conditions. SLs belong to a class of compounds, the g-butyrolactone, known as pheromones or allelochemi- cals: [11] Recently, one of us [12] demonstrated that SLs regu- late protonema branching and act as a quorum sensing-like signal in the moss Physcomitrella patens emphasizing their roles in both plant development and communications be- tween organisms. The structural core of SLs is a tricyclic lac- tone (ABC rings) with various substitution patterns on AB rings. It is connected via an enol ether linkage to an invaria- ble a,b-unsaturated furanone moiety (D-ring) (Scheme 1). To date, at least 15 naturally occurring SLs have been completely identified and characterized in root exudates. It is expected that many other SLs or derivatives will be iden- tified in the future. [1] They are derived from the carotenoid pathway, involving isomerization of b-carotene 1 by a b-car- otene isomerase (D27), and cleavage at the C9’,C10’ posi- tion by Carotenoid Cleavage Dioxygenases 7 (CCD7) to form 9-cis-b-apo-10’-carotenal. Introduction of oxygens and intramolecular rearrangement by CCD8 lead to carlactone 2. [13] Bioactive carlactone 2, very recently isolated, is central for understanding the biosynthesis of SLs but also for con- ceiving SL analogues. It implies that the BC rings are formed after the D ring to give 5-deoxystrigol (3) contrary to a previous hypothesis. [14] This required cyclization was re- cently rationalized [15] by synthetic studies based on a simple linear precursor by an acid-catalyzed double cyclization. Further hydroxylations, epoxidation/oxidation and methyl transfer or acetylation from 3 would lead to hydroxy-SLs or acetylated-SLs: strigol (4), strigyl acetate (4-Ac), orobanchol (5), [16] orobanchyl acetate (5-Ac), solanacol (6) and fabacyl acetate (7), six major hydroxylated and acetylated-SLs found in Nature. Although the synthetic aromatic SL ana- logue GR24 has been known for a long time [17] as a refer- ence compound in bioassays on seed germination of parasit- ic weeds, solanacol (6), the first natural SL containing a Keywords: lactones · plant hor- mones · radical reactions · structure–activity relationships · total synthesis Abstract: A new general access to A-ring aromatic strigolactones, a new class of plant hormones, has been developed. The key transformations include in sequence ring-closing metathesis, enzymatic kinetic resolution and a radical cyclization with atom transfer to install the tricyclic ABC-ring system. The activity as plant hor- mones for the inhibition of shoot branching in pea of various analogues synthe- sized by this strategy is reported. [a] Dr. V.X. Chen, Dr. F.-D. Boyer, Prof. J.-M. Beau Centre de Recherche de Gif Institut de Chimie des Substances Naturelles CNRS, INRA, 1 avenue de la Terrasse, 91198 Gif-sur-Yvette (France) Fax: (+ 33) 1-6907-7247 E-mail: boyer@icsn.cnrs-gif.fr jean-marie.beau@icsn.cnrs-gif.fr [b] Prof. J.-M. Beau UniversitØ Paris-Sud and CNRS Laboratoire de Synthse de BiomolØcules Institut de Chimie MolØculaire et des MatØriaux 91405 Orsay (France) Fax: (+ 33)1-6985-3715 E-mail: jean-marie.beau@u-psud.fr [c] Dr. C. Rameau, J.-P. Pillot IJPB UMR1318 INRA-AgroParisTech RD10, 78126 Versailles Cedex (France) [d] Dr. J.-P. Vors Bayer SAS, 14-20 rue Pierre Baizet BP 99163, 69263 Lyon Cedex 09 (France) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201203585; contains experimen- tal details of all building blocks. Chem. Eur. J. 2013, 19, 4849 – 4857  2013 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim 4849 FULL PAPER