Configuratio n Assignm ent of ۸Į-hydroxy-۱۳-hydro peroxylabd-۱۴,۱۷-dien-۱۹,۱۶;۲۳,۶ Į-diolide by Computed Chem ical Shifts

Some of terpenoids, which a re bicyclic a nd mainly sesterpene lactones, were extracted from Iranian species.۱ R ecently Matloubi and co-workers r eported the partial configuration of a new sestert erpene, ۸Į-hydroxy-۱۳ -hydroperoxylabd-۱۴,۱۷-dien-۱۹,۱ ۶;۲۳,۶Į-diolide.۱ They used their o wn X-ray d etermined c onfiguratio n of norambereinelide-۱۸,۶Į-olide, a member o f this family for the fuse d tricyclic moiety of thi s compound .۱On th e other hand , advanced methods in quantum chemistry facilitate the ra pid, accurat e, and reliabl e calculation of NMR chemical shifts. So, co mparing the calculated and experim ental chemical shifts w ll provide an efficient method in identifying and discrimin ating betwe en the proposed diastere oisomers.۲Considering the a ssigned conf iguration of fused tricy clic moiety, two unassigned stereoc enters allow for totally four possible diastereomers for the target co mpound. They were used as proba ble structures of the target molecule in the quantum mechanical treatments. The first step in this treatment was their co nformation al analyses in order to find candid ate conformers at room temperature which contribute to th e experimental NMR spectra. In the next ste p, the postulated conformers, within a ۳ kCal window of the lowest energy, w ere subjected to extens ive geometry optimization followed by frequency calculations in order to confir m the nature of the opti mized geom etries as min ima and pro vide their computed free energies. In the last step, among t hese extensively optimi zed structure s, those within a ۲.۵ kC al window of the lowest energy w ere subjected to the ch emical shie lding calculations in d imethylsulfoxide solven t. In order to get accurate calculated chemical shieldings, B oltzman-w eighted averaging based on relative free energies of confor mers at ۲۹۸.۱۵ K was used. The relative popul ations of co nformers were computed as Pi Pj  exp  Ei E j RT . Where Px and Ex are the relative popul ation and computed free energy of t he x conformer, respectively.In order to determ ine the correct configuration of the target molecule, the calculated chemical shifts were eval uated according to their largest and correct ed mean a bsolute deviation (CMA D: [ ۱ nin ۱ calc exp ]) in each configuration. In order to confirm the conclusion of the CMAD analysis and get more confidence of which configuration is the correct one, the D P۴ probability analysis developed by Smith and Good man was also employed.۲ Thus according to both the C MAD and DP۴ analyses, structure, shown below , was found to be correct for the target molecule.