Total Synthesis of (−)‐Morphine

Abstract

Asymmetric total synthesis of (-)-morphine has been accomplished in 18 steps from commercially available 7-methoxy-2-tetralone. Our synthesis features a simple transformation from a readily prepared chiral intermediate, construction of the E-ring by acid-mediated cyclization, and singlet oxygen-mediated manipulation of the C-ring. Transformation of the final stage involves construction of the morphinan skeleton by means of 1,6-addition of in situ generated secondary amine.

Interpol review of controlled substances 2016–2019

“…Morphine: 2016 A voltammetric sensor for determination of paracetamol in the presence of morphine [ 313 ]; a short cascade strategy for the stereoselective synthesis of morphine [ 314 ]; extraction of morphine from poppy seeds [ 315 ]; HPLC method for the simultaneous determination of morphine sulfate and naltrexone hydrochloride content in bulk, solid dosage forms [ 316 ]; life cycle assessment from opium poppy farming to the packaging of morphine [ 317 ]; LC-HRMS for the characterization of transformation products and comparison between irradiated samples and those that have not been irradiated [ 318 ]; determination of Morphine in pharmaceutical products by on-line SPE-HPLC [ 319 ]; 2017 solid state vibrational spectroscopic properties of morphine sulfate pentahydrate studied using FTIR-ATR [ 320 ]; review of the research progress on the synthesis of Morphine alkaloids [ 321 ]; Impurity profiling of morphine by LC-HESI-MS [ 322 ]; design and synthesis of carboxylic group functionalized hollow microporous organic capsules for encapsulation of morphine for prolonged release [ 323 ]; characterization of Morphine, Morphine Hydrochloride, and their Hydrates using 1-dimensional and 2-dimensional solid-state NMR and complemented with powder X-ray diffraction, FTIR, and Raman [ 324 ]; one-pot multicomponent approach to synthesize a new series of morphine derivatives [ 325 ]; high-performance thin-layer chromatography-densitometry method for the quantitative analysis of morphine in the tablets of the Ayurvedic medicines [ 326 ]; tandem Brook rearrangement/silicon Polonovski reaction/fragmentation to give formamide derivatives in moderate yields [ 327 ]; asymmetric total synthesis of (−)-morphine [ 328 ]; stability studies of opioid analgesic, morphine-6-O-sulfate in various buffers and biological matrices and analyzed by HPLC-DAD analysis [ 329 ]; Quantum dots (QDs)-labeled antibody fluorescence immunoassays (FLISA) for the rapid detection of morphine for on-site screening of poppy shell added illegally in hot pot soup base [ 330 ]; rapid construction of the 6/6/5 tricyclic framework via a tandem radical cyclization reaction [ 331 ]; Arymo ER - a new abuse deterrent Morphine formulation [ 332 ]; ALERRT((R)) to quantitative measure the effort required to compromise prescription opioid abuse-deterrent tablets [ 333 ]; comparison of the abuse potential of intact and manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with morphine sulfate ER tablets [ 334 ]; compare abuse potential after insufflation of manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine ER tablets [ 335 ]; synthesis of morphinans using a programmed serial stereochemical relay […”

The DARK Side of Total Synthesis: Strategies and Tactics in Psychoactive Drug Production

“…A third, noteworthy synthesis of morphine was reported by the Fukuyama lab in 2017 (Scheme 1c). 34 The synthesis began with the transformation of 7-methoxy-2-tetralone into chiral bicycle (+)-29 using the d'Angelo approach. 35 Elimination of the tertiary alcohol accompanied acid mediated ring closure.…”

“…A third, noteworthy synthesis of morphine was reported by the Fukuyama lab in 2017 (Scheme c) . The synthesis began with the transformation of 7-methoxy-2-tetralone into chiral bicycle (+)- 29 using the d’Angelo approach .…”

Multienzyme One‐Pot Cascades Incorporating Methyltransferases for the Strategic Diversification of Tetrahydroisoquinoline Alkaloids

“…THIQs are an important group of bioactive alkaloids. Alongside their applications as analgesics and antitussives,[ 1 , 2 , 3 , 4 ] THIQs show promise as therapeutics towards cancer, neuropathologies and multi‐drug resistant bacteria. [ 3 , 5 , 6 , 7 , 8 ] However, supply of these compounds for studies and clinical use is limited.…”