Platensimycin Derivatives via Carbonyl Ylide Cycloaddition

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Solution Overview

Problem

Current antibiotics face challenges due to the development of multi-drug resistant bacteria, necessitating the development of new antibiotics with different mechanisms of action, such as platensimycin derivatives that inhibit fatty acid synthesis in bacteria.

Innovation Solution

The development of novel platensimycin derivatives through specific synthetic routes, including tricyclo ketone and tetracyclo derivatives, using carbonyl ylide [3+2] cycloaddition reactions and other organic synthesis steps, to create effective antimicrobial agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional antibiotics are used to treat bacterial infections, then initial treatment effectiveness is achieved, but bacterial resistance develops leading to treatment failure

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidbacterial resistance

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies inversion by developing platensimycin derivatives that target a completely different biological pathway (fatty acid synthesis via FabF inhibition) compared to conventional antibiotics. This reverse approach of attacking pathogens through an alternative mechanism prevents resistance development that occurs when bacteria adapt to traditional antibiotic modes of action

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The patent employs parameter changes by systematically modifying the chemical structure of platensimycin (changing molecular parameters such as substituents at positions R1-R10) to create derivatives with enhanced activity against resistant bacteria. This includes varying alkyl groups, aromatic substituents, and stereochemical configurations to optimize antimicrobial effectiveness

Inventive Principle:

Principle #35Parameter changes

2Device complexity

If platensimycin derivatives are synthesized through traditional multi-step routes, then structural complexity is achieved, but synthesis time and cost increase

Engineering Contradiction:

Improvemolecular structure complexityVSAvoidsynthesis time

Core Design Contradiction:

Device complexityVSLoss of time

Solution Approach 1:

The patent applies preliminary action by pre-synthesizing and storing key intermediates such as tricyclo ketone derivatives and tetracyclo compounds before final assembly. This allows the complex molecular structure to be built from pre-prepared building blocks, reducing the time required for actual derivative synthesis while maintaining structural complexity

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent segments the synthesis into modular stages: first preparing tricyclo ketone intermediates, then converting to tetracyclo derivatives, and finally assembling the complete platensimycin structure. This segmentation allows each complex structural element to be independently optimized and prepared, reducing overall synthesis time

Inventive Principle:

Principle #1Segmentation

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

These derivatives demonstrate broad antimicrobial activity, including against resistant bacteria like MRSA and VRE, offering a promising solution to treat infections effectively.

Implementation Method 1

tricyclo ketone derivatives represented by formula 10 or formula 24 and a preparing method of the same and a preparing method of tetracyclo derivatives represented by formula 4 or formula 19. Tricyclo ketone derivatives are produced from diazoketone derivatives via carbonyl ylide [3+2] cycloaddition reaction

Methodology Applied

Scientific EffectCarbonyl ylide [3+2] cycloaddition reaction: Chemical Bonding

Data Source

PatentUS8471043B2Platensimycin derivatives, their intermediates, and process for preparing the same, and new process for preparing platensimycin

Publication Date: 2013.06.25 SEOUL NATIONAL UNIVERSITY R&DB FOUNDATION

AI summary

The present invention relates to novel platensimycin derivatives, their intermediates and preparing methods of the same. Platensimycin is known as an effective antibiotic material having a broad antimicrobial spectrum and its derivatives are also expected to be effective antibiotic candidates. The present invention also relates to a novel preparing method of platensimycin. The intermediates used for the production of platensimycin and its derivatives of the present invention are tricyclo ketone derivatives and tetracyclo derivatives. Tetracyclo derivatives are prepared from tricyclo ketone derivatives prepared by carbonyl ylide [3+2] cycloaddition of dia-zoketone derivative.