Author's personal copy W. Li et al./Bioorg Med. Chem. Lett. 20(2010)418-421 HcO OCH Morphine Etorphine Figure 1. The structures of thebaine, morphine, diprenorphine and etorphine. H3 =CH2 xylene, refle thebaine adducts adducts O-NO2 m-NO Scheme 1. The Diels-Alder reactions of thebaine and styrenes Sc19 Figure 2. X-ray crystal structures of compound-4(left)and-5(right). regioisomeric So-adducts, since these dienophiles are al heterotrimeric G protein, and has been used as a functional mea- of polarizing functionality in their structures which are sure for determination of potencies and efficacies of agonists. Thus, the agonistic activities of these compounds were determined by though other factors such as solvent, harsh conditions regulation of the binding of (5S]GTPyS(Table 3). Since most com effects, the trend of Diels-Alder reactions forwarded to main 7a- pounds have no undetectable affinities for 8-and k-opioid recep- adducts has not changed in all of these cases up to 10 HM Affinities of these compounds to opioid receptors were ompetitive inhibition of HJ (Table 2) Ligand regulation of the binding of BSS]GTPyS is one been shown in Table 2 and the agonistic activity of th he most widely used methods to measure receptor activation of compounds for u opioid receptors has been shown in Table 3Author's personal copy regioisomeric 8a-adducts, since these dienophiles are also devoid of polarizing functionality in their structures which are different to other dienophiles such as 3-buten-2-one and acrylonitrile. Although other factors such as solvent, harsh conditions may take effects, the trend of Diels–Alder reactions forwarded to main 7a￾adducts has not changed in all of these cases. Affinities of these compounds to opioid receptors were deter￾mined by competitive inhibition of [3 H] diprenorphine binding (Table 2). Ligand regulation of the binding of [35S]GTPcS is one of the most widely used methods to measure receptor activation of heterotrimeric G protein, and has been used as a functional mea￾sure for determination of potencies and efficacies of agonists. Thus, the agonistic activities of these compounds were determined by regulation of the binding of [35S]GTPcS (Table 3). Since most com￾pounds have no undetectable affinities for d- and j-opioid recep￾tors at the concentrations up to 10 lM, only l opioid receptor was employed in the functional assays. The binding profiles of these compounds for three types of opioid receptors (l, d, j) have been shown in Table 2 and the agonistic activity of these compounds for l opioid receptors has been shown in Table 3. CH=CH2 R thebaine xylene, reflux N CH3 H3CO O H3CO 7α-adducts N CH3 H3CO O H3CO 8α-adducts + R R R= H o-NO2 m-NO2 p-NO2 1 3 4 6 2 5 7 Scheme 1. The Diels–Alder reactions of thebaine and styrenes. N O H3C H3CO OCH3 Thebaine N O H3C HO OH Morphine 7 8 Diprenorphine N HO O OCH3 C(CH3)2OH 7 8 Etorphine N CH3 HO O OCH3 OH CH3 CH2CH2CH3 Figure 1. The structures of thebaine, morphine, diprenorphine and etorphine. Figure 2. X-ray crystal structures of compound-4(left) and -5(right). W. Li et al. / Bioorg. Med. Chem. Lett. 20 (2010) 418–421 419