Application of the Mitsunobu Reaction for the Preparation of Isomorphine and Isocodeine Derivatives

Simon, Csaba; Hosztafi, Sándor; Makleit, S.

doi:10.1080/00397919108016763

Cited by 17 publications

(3 citation statements)

References 12 publications

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“…An amine moiety was subsequently introduced into the 6-position to provide a point of attachment which retains the capacity to act as a hydrogen bond donor as per the 6-OH of morphine after the linker has been attached. 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. − 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 7 . A comparison of the NMR spectra of compounds 6 and 7 (Supporting Information, Figure S1) demonstrated stereospecific inversion of this chiral center.…”

Section: Resultsmentioning

confidence: 99%

Fluorescently Labeled Morphine Derivatives for Bioimaging Studies

Lam

Gondin

Canals³

et al. 2018

J. Med. Chem.

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Opioids, like morphine, are the mainstay analgesics for the treatment and control of pain. Despite this, they often exhibit severe side effects that limit dose; patients often become tolerant and dependent on these drugs, which remains a major health concern. The analgesic actions of opioids are primarily mediated via the μ-opioid receptor, a member of the G protein-coupled receptor superfamily. Thus far, development of small molecule fluorescent ligands for this receptor has resulted in antagonists, somewhat limiting the use of these probes. Herein, we describe our work on the development of a small molecule fluorescent probe based on the clinically used opiate morphine and initial characterization of its behavior in cell-based assays.

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Section: Resultsmentioning

confidence: 99%

Fluorescently Labeled Morphine Derivatives for Bioimaging Studies

Lam

Gondin

Canals³

et al. 2018

J. Med. Chem.

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“…However, only few reports have been published on their novel derivatives. In 1991, Simon et al reported novel analogues of isocodeine and isomorphine by the employment of the Mitsunobu reaction [ 101 ]. The reaction was started from different N -substituted analogues of isocodeine and isomorphine.…”

Section: Disubstituted Derivativesmentioning

confidence: 99%

Synthesis and Modification of Morphine and Codeine, Leading to Diverse Libraries with Improved Pain Relief Properties

Zarin,

Dehaen,

Salehi

et al. 2023

Pharmaceutics

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Morphine and codeine, two of the most common opioids, are widely used in the clinic for different types of pain. Morphine is one of the most potent agonists for the μ-opioid receptor, leading to the strongest analgesic effect. However, due to their association with serious side effects such as respiratory depression, constriction, euphoria, and addiction, it is necessary for derivatives of morphine and codeine to be developed to overcome such drawbacks. The development of analgesics based on the opiate structure that can be safe, orally active, and non-addictive is one of the important fields in medicinal chemistry. Over the years, morphine and codeine have undergone many structural changes. The biological investigation of semi-synthetic derivatives of both morphine and codeine, especially morphine, shows that studies on these structures are still significant for the development of potent opioid antagonists and agonists. In this review, we summarize several decade-long attempts to synthesize new analogues of morphine and codeine. Our summary placed a focus on synthetic derivatives derived from ring A (positions 1, 2, and 3), ring C (position 6), and N-17 moiety.

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“…The researchers utilized the observation that 54 formed 7 -halo-neopine (61, 62, X=Cl, Br, respectively) with concentrated hydrohalic acids, thus the favourable elimination of the 6-substituent led to 59 and 60. They also carried out the rearrangement of these morphinandienes into 3-haloaporphines [105]. …”

Section: -Halomorphinandienesmentioning

confidence: 99%

Recent Developments in the Chemistry of Thebaine and its Transformation Products as Pharmacological Targets

Berényi¹,

Csutorás²,

Sipos

2009

CMC

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The most practical synthetic routes to the preparation of as important pharmaceuticals as oxycodone, naloxone, naltrexone, nalbuphine and buprenorphine have utilized the alkaloid, thebaine, as a starting material. This review intends to focus on chemical transformations of morphinans which resulted in morphinandiene derivatives with well-established and novel pharmacological potencies. These chemical transformations were mainly associated with the formation and substitution of the unique diene structure of the ring C of the morphinan backbone.

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Application of the Mitsunobu Reaction for the Preparation of Isomorphine and Isocodeine Derivatives

Cited by 17 publications

References 12 publications

Fluorescently Labeled Morphine Derivatives for Bioimaging Studies

Fluorescently Labeled Morphine Derivatives for Bioimaging Studies

Synthesis and Modification of Morphine and Codeine, Leading to Diverse Libraries with Improved Pain Relief Properties

Recent Developments in the Chemistry of Thebaine and its Transformation Products as Pharmacological Targets

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