Studies on Morphinan Derivatives. II. The Synthesis of d-3-Methyl-N-methylmorphinan, a New Antitussive

Murakami, Masuo; Kawahara, Shun‐ichi; Inukai, Noriyoshi; Nagano, Noriaki; Iwamoto, Hidenori; Ida, Hisashi

doi:10.1248/cpb.20.1706

Cited by 8 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is only one synthesis of DF reported in 1972. 20,21) The overall yield for preparation of DF was only 15% and it took 70 h to cyclize the requisite ring system by phosphoric acid. 20,21) Thus, it is a primary goal to provide a novel method toward DF.…”

Section: Resultsmentioning

confidence: 99%

“…20,21) The overall yield for preparation of DF was only 15% and it took 70 h to cyclize the requisite ring system by phosphoric acid. 20,21) Thus, it is a primary goal to provide a novel method toward DF. We envisioned that this compound might be more readily prepared by using commercially available 3-hydroxymorphinan (3, 3-HM) as a starting material (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Concise Synthesis of Dimemorfan (DF) Starting from 3-Hydroxymorphinan (3-HM)

Kim

et al. 2008

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Dimemorfan (DF) has been known to possess neuroprotective properties. While this promising compound deserves further biological evaluation, synthetic methods have not improved since Murakami group unveiled the synthetic efforts in 1972. Herein a succinct synthesis toward DF from commercially available 3-hydroxymorphinan (3-HM) is disclosed. Other morphinan analogs have been effectively prepared by adopting the similar methodology.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Concise Synthesis of Dimemorfan (DF) Starting from 3-Hydroxymorphinan (3-HM)

Kim

et al. 2008

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

show abstract

“…It is 1.5 times as potent Vol. 10 Cough Remediesan antitussive as dextromethorphan, with some analgesic activity and minimal side effects [18]. Trade Names.…”

Section: Morphinansmentioning

confidence: 99%

“…Sodium Dibunate is a mixture of the sodium salts of 3,7-and 3,6-di-tert-butyl-1-naphthalenesulfonic acid (dibunate, C 18 Dibunate is obtained by sulfonation of 2,7-ditert-butylnaphthalene with chlorosulfuric acid. The reaction is accompanied by partial rearrangement of one tert-butyl group [56].…”

Section: Piperazine Derivativesmentioning

confidence: 99%

Cough Remedies

Bub¹,

Friedrich²

2000

Ullmann's Encyclopedia of Industrial Chemistry

View full text Add to dashboard Cite

The article contains sections titled: 1. Introduction 2. Antitussives 2.1. Antitussives Acting on the Central Nervous System 2.1.1. Alkaloids and Derivatives 2.1.2. Morphinans 2.1.3. Arylalkylamines 2.1.4. Basic Esters 2.1.5. Basic Ethers 2.1.6. Piperazine Derivatives 2.1.7. Other Compounds 2.2. Antitussives Acting Mainly Peripherally 3. Expectorants 3.1. Secretolytics and Secretomotorics 3.2. Mucolytics 3.2.1. Cysteine Derivatives 3.2.2. Benzylamines

show abstract

“…Various methods for the synthesis of these compounds have been previously reported. Kinetic resolution of the racemic amines has been used to access their optically pure forms, [4] but it is economically and ecologically unattractive due to the maximum yield of 50%. Transition-metal complexes such as iridium and ruthenium have been reported to catalyze the asymmetric transfer hydrogenation of the corresponding (Z)-enamide or iminium salts in high ee values and yields.…”

Section: Introductionmentioning

confidence: 99%

Imine Reductase‐Catalyzed Enantioselective Reduction of Bulky α,β‐Unsaturated Imines en Route to a Pharmaceutically Important Morphinan Skeleton

Yao

Sheng

et al. 2018

Adv Synth Catal

View full text Add to dashboard Cite

The morphinan skeleton is an important sub-structure in many medicines such as dextromethorphan, and can be constructed from 1-benzyl-1,2,3,4,5,6,7,8-octahydroisoquinoline (1-benzyl-OHIQ) derivatives. 1-Benzyl-3,4,5,6,7,8-hexahydroisoquinolines (1-benzyl-HHIQs), the precursors of 1-benzyl-OHIQs, constitute a type of bulky a, b-unsaturated imines. Until now, the application of imine reductases (IREDs) to a, b-unsaturated imines has only rarely been reported. In this study, through evaluation of 48 IREDs, both enantiomers of 1-(4-methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline (1-(4-methoxybenzyl)-OHIQ) were obtained in high yield and excellent optical purity. Among the enzymes, the most steric hindrance-tolerant IRED from Sandarearacinus amylolyticus (IR40) was able to convert various phenyl substituted 1-benzyl-HHIQ to the corresponding 1-benzyl-OHIQ derivatives with excellent enantiometric excess. These results provide an effective route to synthesize these important compounds via enantioselective reduction of bulky a, b-unsaturated imine precursors, which can be readily prepared from 2-(1-cyclohexenyl) ethylamine and corresponding aryl acetic acids.

show abstract

Studies on Morphinan Derivatives. II. The Synthesis of d-3-Methyl-N-methylmorphinan, a New Antitussive

Cited by 8 publications

References 0 publications

Concise Synthesis of Dimemorfan (DF) Starting from 3-Hydroxymorphinan (3-HM)

Concise Synthesis of Dimemorfan (DF) Starting from 3-Hydroxymorphinan (3-HM)

Cough Remedies

Imine Reductase‐Catalyzed Enantioselective Reduction of Bulky α,β‐Unsaturated Imines en Route to a Pharmaceutically Important Morphinan Skeleton

Contact Info

Product

Resources

About