Pactalactam Total Synthesis Reducing Cytotoxicity

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Conventional pactamycin compounds exhibit strong cytotoxicity, limiting their use as anticancer drugs, necessitating the development of non-toxic analogs with similar antibacterial and anticancer effects.

Innovation Solution

A total synthesis method for pactalactam involving a series of organic reactions starting from a phenyloxazoline derivative, converting it into a cyclopentenone derivative, then an N-PMB aziridine, an oxazoline derivative with a cyclopentane core, and finally pactalactam, using solvents like acetic acid and THF, to produce a non-toxic compound with antiviral, antibacterial, and anticancer properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If pactamycin analogs are developed to maintain antibacterial and anticancer effects, then biological activity is improved, but cytotoxicity increases

Engineering Contradiction:

Improvebiological activityVSAvoidcytotoxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by making specific modifications to particular regions of the pactamycin molecule. The invention introduces a lactam ring structure at specific positions (C-3' and C-4' or C-3' and C-5') while maintaining other functional groups intact, thereby locally altering the molecular properties to reduce cytotoxicity while preserving the core antibacterial and anticancer activities

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs parameter changes by systematically varying structural parameters of the pactamycin analogs, specifically changing the ring structure from the original pactamycin configuration to lactam ring configurations. This structural parameter modification results in compounds with altered biological properties, achieving reduced cytotoxicity while maintaining therapeutic efficacy

Inventive Principle:

Principle #35Parameter changes

2Object-affected harmful factors

If novel non-toxic analogs are synthesized to reduce cytotoxicity, then safety is improved, but structural complexity increases

Engineering Contradiction:

ImprovecytotoxicityVSAvoidstructural complexity

Core Design Contradiction:

Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the molecule modification into distinct segments or regions. The lactam ring is introduced as a separate structural segment at specific positions on the pactamycin core, allowing independent optimization of this segment for reduced toxicity while leaving other segments intact to maintain biological activity

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent uses composite material principles by creating hybrid molecular structures that combine the original pactamycin framework with additional lactam ring structures. This composite approach integrates the beneficial properties of both the parent compound (antibacterial and anticancer activity) and the modified structure (reduced cytotoxicity) into a single molecule

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS11345667B2Total synthesis method of pactalactam

Publication Date: 2022.05.31 KOREA INST OF SCI & TECH

AI summary

The present invention relates to a method of preparing pactalactam represented by Formula 5 below using a total synthesis method: