Phragmalin Limonoid Synthesis via Segmented Ring Opening and Closing

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Solution Overview

Problem

The synthesis of compounds with sexual enhancing activity, particularly those with structure (1), is hindered by their rarity in plants, difficulty in isolation, and the complexity of ring opening and closing reactions, leading to low yields and excessive side products using conventional methods.

Innovation Solution

A novel process is developed to efficiently synthesize compounds with structure (1) and (5) using distinct conditions and reagents, achieving chemoselectivity and regioselectivity, and providing a high-yield route from readily available starting materials, including the conversion of compound (2a) to (1) and (5), and inducing aggressive behavior in mammals.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional isolation methods are used to obtain compounds with structure (1), then the compounds can be obtained, but the process is difficult and expensive with low yields due to rarity in plants

Engineering Contradiction:
ImproveyieldVSAvoiddifficulty of isolation
Core Design Contradiction:
Quantity of substanceVSEase of manufacture

Solution Approach 1:

The synthesis is divided into multiple discrete steps: ring opening of the lactone ring in compound (2a) to form intermediate (3), followed by ring closing to form compound (1). This segmentation allows each step to be optimized independently, improving overall yield and feasibility.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

A novel intermediate compound with structure (3) is introduced as a bridge between the readily available starting material (2a) and the target compound (1). This intermediary enables the transformation through manageable steps rather than attempting direct conversion.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Quantity of substance

If conventional ring opening and closing methods are used, then the transformation can be achieved, but excessive side products are formed and yields are low

Engineering Contradiction:
ImproveyieldVSAvoidside products
Core Design Contradiction:
Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

Distinct reaction conditions and reagents are employed for the ring opening and ring closing steps, optimizing parameters such as temperature, solvent, and catalyst to maximize selectivity and minimize side product formation.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent transforms the challenge of ring opening and closing reactions, which conventionally produce excessive side products, into a high-yield process by using novel reagents and conditions that selectively drive the desired transformations while suppressing unwanted side reactions.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

3Ease of manufacture

If full synthesis of compound (1) is attempted using conventional methods, then the target compound can be produced, but the process is very difficult and has not been successfully attempted thus far

Engineering Contradiction:
Improvefeasibility of synthesisVSAvoidcomplexity of synthesis process
Core Design Contradiction:
Ease of manufactureVSDevice complexity

Solution Approach 1:

The lactone ring in compound (2a) is opened in advance to form intermediate (3) before the ring closing step. This preliminary action simplifies the overall synthesis by breaking down the complex transformation into preparatory and final steps, making the process feasible.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The complex synthesis is segmented into distinct manageable steps: ring opening to form intermediate (3), followed by ring closing to form compound (1). This segmentation reduces the overall complexity and makes the synthesis achievable through systematic approach.

Inventive Principle:
Principle #1Segmentation

Data Source

PatentEP2807170B1Phragmalin limonoids for the treatment of sexual dysfunction
Publication Date: 2019.03.13 DICOT AB
  • EP2807170B1 patent drawingFigure 1
  • EP2807170B1 patent drawingFigure 2
  • EP2807170B1 patent drawingFigure 3

AI summary

The present invention relates to novel chemical compounds, to methods for synthesis of such compounds, and to the use of these novel compounds in the synthesis of other chemical compounds that, inter alia, may be used in the treatment of sexual dysfunction, and for eliciting enhancing effects on sexual behavior. The invention also relates to remarkable biological properties of the novel compounds in their capacity of inducing aggressive behavior.