28973-48-0Relevant academic research and scientific papers
Contra-thermodynamic Hydrogen Atom Abstraction in the Selective C-H Functionalization of Trialkylamine N-CH3 Groups
Barham, Joshua P.,John, Matthew P.,Murphy, John A.
, p. 15482 - 15487 (2016/12/09)
We report a simple one-pot protocol that affords functionalization of N-CH3 groups in N-methyl-N,N-dialkylamines with high selectivity over N-CH2R or N-CHR2 groups. The radical cation DABCO+?, prepared in situ by oxidation of DABCO with a triarylaminium salt, effects highly selective and contra-thermodynamic C-H abstraction from N-CH3 groups. The intermediates that result react in situ with organometallic nucleophiles in a single pot, affording novel and highly selective homologation of N-CH3 groups. Chemoselectivity, scalability, and recyclability of reagents are demonstrated, and a mechanistic proposal is corroborated by computational and experimental results. The utility of the transformation is demonstrated in the late-stage site-selective functionalization of natural products and pharmaceuticals, allowing rapid derivatization for investigation of structure-activity relationships.
An improved process for the preparation of (+)-3- Methoxy-N-formylmorphinan
Kumaraguru, Thenkrishnan,Fadnavis, Nitin W.
, p. 174 - 178 (2014/05/20)
Two major steps, N-formylation of (-)-octabase and cyclization of the N-formylated product, involved in synthesis of (+)-3-methoxy-N-formylmorphinan, a key intermediate for production of dextromethorphan (DXM), have been improved to achieve higher yields in shorter time with fewer effluents. Methods of analysis of chemical and enantiomeric purities of the intermediates by HPLC and strategies for easy recovery and recycle of the reagents have been devised.
Dextrorphan. Note II. Preparation of dextrorphan citrate
Passarotti,Valenti,Grianti
, p. 475 - 477 (2007/10/02)
Preparation of destrorphan citrate, a very soluble salt in water, in described. This salt may be used in oral composition with anti-tussive activity. Structural date are reported about 1H-NMR, 13C-NMR, COSY.
Synthesis and Evaluation of 3-Substituted 17-Methylmorphinan Analogs as Potential Anticonvulsant Agents
Newman, Amy Hauck,Bevan, Kathryn,Bowery, Norman,Tortella, Frank C.
, p. 4135 - 4142 (2007/10/02)
Dextromethorphan (1, (+)-3-methoxy-17-methylmorphinan) demonstrates anticonvulsant activity in a variety of in vitro and in vivo models of convulsive action.It is well known that 1 is metabolized to its phenolic derivative dextrorphan (2) and this metabolite is also a potent anticonvulsant.A series of (+)-3-substituted-17-methylmorphinans, which are structurally similar to 1 but are either not expected to be metabolized to 2 or might do so at a reduced rate, as compared to 1, were prepared.Three analogs, 5 ((+)-3-amino-17-methylmorphinan), 14 ((+)-3-ethoxy-17-methylmorphinan), and 15 ((+)-3-(2-propoxy)-17-methylmorphinan were found to possess potent anticonvulsant activity with full efficacy (ED50 25, 5.6, and 3.9 mg/kg, sc, respectively) in the rat supramaximal electroshock (MES) test.Binding potencies of these compounds to receptor sites labeled with 3H>dextromethorphan (3H>1), in rat brain and guinea pig brain subcellular fractions, and 3H>thienylcyclohexylpiperidine (TCP) and 3H>glycine in rat brain, were determined.Most of the analogs displaced 3H>1 from its binding sites, with compounds 14 (IC50 0.42 μM) and 15 (IC50 0.88 μM having equivalent potencies to 1 (IC50 0.59 μM), in rat brain, and no appreciable activity at the 3H>TCP or 3H>glycine-labeled sites.Compound 5 did not bind with appreciable activity to the 3H>1 site, in rat brain, but did bind to the 3H>TCP site with lower potency than the parent 1 (IC50 7.8 and 2.0 μM, respectively).The mechanism of anticonvulsant action of these agents is not clear although it appears that interaction at the 3H>1 sites may be involved.
ELECTRON-TRANSFER ACTIVATION. SALT EFFECTS ON THE PHOTOOXADIDATION OF TERTIARY AMINES : A USEFUL N-DEMETHYLATION METHOD
Santamaria, J.,Ouchabane, R.,Rigaudy, J.
, p. 3977 - 3980 (2007/10/02)
Photooxidation of tertiary methylamines sensitized by electron acceptors like 9,10-dicyanoanthracene is shown to proceed by two distinct ways depending on the presence of added salts.In the absence of added salt both nor and N-formyl compounds were obtained while with added salt the nor-derivative is obtained highly efficiently.
GENERAL ASYMMETRIC SYNTHESIS OF BENZOMORPHANS AND MORPHINANS VIA ENANTIOSELECTIVE HYDROGENATION
Kitamura, M.,Hsiao, Yi,Noyori, R.,Takaya, H.
, p. 4829 - 4832 (2007/10/02)
A variety of optically active benzomorphans including metazocine and pentazocine as well as dextromethorphan, a morphinan, are obtainable by using the BINAP-ruthenium(II) catalyzed enantioselective hydrogenation as key operation.
