Stereoselective synthesis of β-naltrexol, β-naloxol β-naloxamine, β-naltrexamine and related compounds by the application of the mitsunobu reac

Fluorescently Labeled Morphine Derivatives for Bioimaging Studies

“…As we also wished to maintain the native stereochemistry of the C-6 position a double Mitsunobu approach was employed to install this amine, noting that the Mitsunobu reaction has previously been reported to invert this stereocenter in closely related opiates. [22][23][24][25] Accordingly, 6-OH was first inverted using benzoic acid under Mitsunobu conditions followed by saponification of the resultant ester to give the 6-isomorphine derivative Two different approaches for ester and amide conjugation were trialed. The first, using an acid chloride, yielded compounds 1 and 3 following phenolic deprotection (Scheme 2).…”

“…These data suggest that the probe compound 21 may be a used as a tool compound to simulate the behavior of morphine, much in the same way DERM-A594 is used as a tool compound for the study of endogenous opioid peptides. 15 It is clear that morphine has significantly different signaling profile compared to peptides, 23,24 and therefore small molecule-based fluorescent probes may lead to different outcomes compared to studies where fluorescent peptides have been utilized.…”

Controlling opioid receptor functional selectivity by targeting distinct subpockets of the orthosteric site

“…The codeine phthalimides one was prepared from morphine in two steps according to the literature procedures. The reduction of codeine phthalimides in the presence of Pd/C and hydrogen followed by phthalimide group removal using excess of hydrazine hydrate gave the β-dihydrocodeine amine 2 ( Crooks et al, 2006 ; Simon et al, 1994 ; Simon et al, 1992 ). The β-dihydrocodeine amine two was treated to m -iodobenzoic acid in the presence coupling reagent HATU with an organic base DIPEA to furnish corresponding m -iodoarylamidomorphinan 3.…”

“…Finally, O -demethylation in five was performed using standard BBr 3 demethylation protocol to obtain MP1202 ( Váradi et al, 2015a ). On the other hand, MP1207–MP1208 were prepared ( Appendix 1—scheme 1B ) using 6 (β-dihydro N-CPM morphineamine) which was prepared form morphine in seven steps using known protocols ( Simon et al, 1994 ; Simon et al, 1992 ). In addition, di-Boc-guanidinomethyl benzoic acid eight was prepared by reacting amino methyl benzoic acid with N , N ′- di -Boc-1 H -pyrazole-1-carboxamidine at 50°C ( Robinson and Roskamp, 1997 ).…”

Characteristics of TRK-130 (Naltalimide), a Novel Opioid Ligand, as a New Therapeutic Agent for Overactive Bladder

“…TRK-130 was synthesized at Pharmaceutical Research Laboratories, Toray Industries (Kanagawa, Japan), according to a procedure, for example, described in previous literature (Simon et al, 1994). Morphine was obtained from Takeda Pharmaceutical (Osaka, Japan).…”