14509-92-3

Usage

Uses

1. Used in Pharmaceutical Industry:
(3β,16E)-16,17-Didehydro-9,17-dimethoxycorynan-16-carboxylic acid methyl ester is used as a pharmaceutical compound for its potential therapeutic applications. The compound's unique structure and properties make it a promising candidate for the development of new drugs targeting various health conditions.
2. Used in Chemical Research:
In the field of chemical research, (3β,16E)-16,17-Didehydro-9,17-dimethoxycorynan-16-carboxylic acid methyl ester serves as a valuable compound for studying its chemical properties, reactivity, and potential interactions with other molecules. This research can lead to a better understanding of its applications and the development of new synthetic methods or derivatives with improved properties.
3. Used in Drug Delivery Systems:
Similar to gallotannin, (3β,16E)-16,17-Didehydro-9,17-dimethoxycorynan-16-carboxylic acid methyl ester can be employed in drug delivery systems to enhance its bioavailability and therapeutic outcomes. By incorporating the compound into various carriers, such as organic or metallic nanoparticles, its delivery, efficacy, and targeting to specific cells or tissues can be improved.
4. Used in Anticancer Applications:
Although not explicitly mentioned in the provided materials, given the compound's potential pharmaceutical applications, it could also be investigated for its anticancer properties. If found to have significant effects on tumor growth and progression, (3β,16E)-16,17-Didehydro-9,17-dimethoxycorynan-16-carboxylic acid methyl ester could be used as an anticancer agent, targeting specific cancer cells and modulating oncological signaling pathways.

References

Beckett, Shellard, Tackie., J. Pharm. Pharmacal. Suppl., 15, 166T (1963)Beckett, Tackie., ibid, 15, 267T (1963)Absolute configuration: Lee, Trager, Beckett., Tetrahedron, 23, 375 (1967)

Upstream product

• 951327-94-9 (2R,3S,12bS)-tert-butyl 3-ethyl-8-methoxy-2-(2-methoxy-2-oxoethyl)-1,2,3,4,6,7-hexahydroindolo[2,3-a]quinolizine-12(12bH)-carboxylate 
• 107-31-3 Methyl formate 
• 149-73-5 trimethyl orthoformate 
• 77-78-1 dimethyl sulfate 
• 4837-90-5 4-methoxy-1H-indole 
• 951327-93-8 methyl 2-((2R,3S,12bS)-3-ethyl-8-methoxy-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizin-2-yl)acetate 
• 4359-77-7 3-ethyl-3-buten-2-one 
• 99115-96-5 3-ethyl-4-hydroxy-2-butanone 
• 210359-35-6 2-(2-methyl-1,3-dioxolan-2-yl)butan-1-ol 
• 51756-08-2 methyl 2-ethyl-3-oxobutanoate 
• 285983-16-6 N-(2-(4-methoxy-1H-indol-3-yl)ethyl)formamide 
• 3610-35-3 4-methoxytryptamine 
• 83788-92-5 (E)-4-methoxy-3-(2-nitrovinyl)-1H-indole 
• 90734-97-7 4-methoxyindole-3-carboxaldehyde 

Downstream Products

• 174418-82-7 Mitragynine hydroxyindolenine 
• 174418-81-6 O-Acetylmitragynine hydroxyindolenine 
• 23407-35-4 methyl (E)-2-((2S,3S,12bS)-3-ethyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizin-2-yl)-3-methoxyacrylate 

Relevant academic research and scientific papers

MITRAGYNINE ANALOGS FOR THE TREATMENT OF PAIN, MOOD DISORDERS AND SUBSTANCE USE DISORDERS

The present invention provides a compound having the structure (I): or a pharmaceutically acceptable salt or ester thereof, and a method of treating a subject afflicted with pain a depressive disorder, a mood disorder or an anxiety disorder by administering the compound to the subject.

MITRAGYNINE ALKALOIDS AS OPIOID RECEPTOR MODULATORS

The present invention provides a compound having the structure: or a pharmaceutically acceptable salt or ester thereof, and a method of treating a subject afflicted with pain, a depressive disorder, a mood disorder or an anxiety disorder by administering the compound to the subject.

Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators

Mu-opioid receptor agonists represent mainstays of pain management. However, the therapeutic use of these agents is associated with serious side effects, including potentially lethal respiratory depression. Accordingly, there is a longstanding interest in the development of new opioid analgesics with improved therapeutic profiles. The alkaloids of the Southeast Asian plant Mitragyna speciosa, represented by the prototypical member mitragynine, are an unusual class of opioid receptor modulators with distinct pharmacological properties. Here we describe the first receptor-level functional characterization of mitragynine and related natural alkaloids at the human mu-, kappa-, and delta-opioid receptors. These results show that mitragynine and the oxidized analogue 7-hydroxymitragynine, are partial agonists of the human mu-opioid receptor and competitive antagonists at the kappa- and delta-opioid receptors. We also show that mitragynine and 7-hydroxymitragynine are G-protein-biased agonists of the mu-opioid receptor, which do not recruit β-arrestin following receptor activation. Therefore, the Mitragyna alkaloid scaffold represents a novel framework for the development of functionally biased opioid modulators, which may exhibit improved therapeutic profiles. Also presented is an enantioselective total synthesis of both (-)-mitragynine and its unnatural enantiomer, (+)-mitragynine, employing a proline-catalyzed Mannich-Michael reaction sequence as the key transformation. Pharmacological evaluation of (+)-mitragynine revealed its much weaker opioid activity. Likewise, the intermediates and chemical transformations developed in the total synthesis allowed the elucidation of previously unexplored structure-activity relationships (SAR) within the Mitragyna scaffold. Molecular docking studies, in combination with the observed chemical SAR, suggest that Mitragyna alkaloids adopt a binding pose at the mu-opioid receptor that is distinct from that of classical opioids.

Total syntheses of mitragynine, paynantheine and speciogynine via an enantioselective thiourea-catalysed Pictet-Spengler reaction

The pharmacologically interesting indole alkaloids (-)-mitragynine, (+)-paynantheine and (+)-speciogynine were synthesised in nine steps from 4-methoxytryptamine by a route featuring (i) an enantioselective thiourea-catalysed Pictet-Spengler reaction, providing the tetrahydro-β- carboline ring and (ii) a Pd-catalysed Tsuji-Trost allylic alkylation, closing the D-ring. The Royal Society of Chemistry 2012..

Indole Alkaloid Derivatives Having Opioid Receptor Agonistic Effect, and Therapeutic Compositions and Methods Relating to Same

Indole alkaloid derivatives having an opioid receptor agonistic effect, their synthesis, and therapeutic compositions containing these derivatives, and methods of treating conditions with these compounds and therapeutic compositions, are provided.

General approach to the total synthesis of 9-methoxy-substituted indole alkaloids: Synthesis of mitragynine, as well as 9-methoxygeissoschizol and 9-methoxy-Nb-methylgeissoschizol

(Chemical Equation Presented) Herein, the full details of the synthesis of the 9-methoxy-substituted Corynanthe indole alkaloids mitragynine (1), 9-methoxygeissoschizol (3), and 9-methoxy-Nb-methylgeissoschizol (4) are described. Initially, an efficient synthetic route to the optically active 4-methoxytryptophan ethyl ester 20 on a multigram scale was developed via a Mori-Ban-Hegedus indole synthesis. The ethyl ester of D-4-methoxytryptophan 20 was obtained with a radical-mediated regioselective bromination of indoline 12 serving as a key step. Alternatively, the key 4-methoxytryptophan intermediate 22 could be synthesized by the Larock heteroannulation of aryl iodide 10b with the internal alkyne 21a. The use of the Boc-protected aniline 10b was crucial to the success of this heteroannulation. The α,β-unsaturated ester 6 was synthesized via the Pictet-Spengler reaction as the pivotal step. This was followed by a Ni(COD)2-mediated cyclization to set up the stereocenter at C-15. The benzyloxy group in 31 was removed to provide the intermediate ester 5. This chiral tetracyclic ester 5 was employed to accomplish the first total synthesis of 9-methoxygeissoschizol (3) and 9-methoxy-N b-methylgeissoschizol (4) as well as the opioid agonistic indole alkaloid mitragynine (1).

Total synthesis of the opioid agonistic indole alkaloid mitragynine and the first total syntheses of 9-methoxygeissoschizol and 9-methoxy-N b-methylgeissoschizol

An enantiospecific method for the synthesis of 4-methoxytryptophan has been developed via a regiospecific Larock heteroannulation and employed for the first total syntheses of 9-methoxygeissoschizol and 9-methoxy-N b-methylgeissoschizol, as well as the total synthesis of the opioid agonistic alkaloid mitragynine. The asymmetric Pictet-Spengler reaction and a Ni(COD)2-mediated cyclization served as key steps.

New procedure to mask the 2,3-π bond of the indole nucleus and its application to the preparation of potent opioid receptor agonists with a corynanthe skeleton

(Diagram presented) Treatment of indole alkaloids with hypervalent iodine in the presence of ethylene glycol provides 2,3-ethylene glycol bridged adducts that could be converted into the original indoles under mild reductive conditions. This procedure, which involves masking of the reactivity of the indole nucleus at the β-position, was utilized for the modification of the benzene ring of the indoline derivative and was applied to the preparation of potent opioid receptor agonists with the Corynanthe skeleton.

The first total synthesis of (-)-mitragynine, an analgesic indole alkaloid in Mitragyna speciosa

Starting from an optically pure alcohol, (R)-(3), which was prepared by enzymatic hydrolysis of the racemic acetate (2) or enantioselective reduction of the ketone derivative (4), the chiral total synthesis of mitragynine (1), a major corynanthe-type indole alkaloid having an analgesic effect in Mitragyna speciosa, was accomplished.