Lycopene Synthesis via C15-Wittig Salt Purification

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Solution Overview

Problem

Conventional synthesis processes for producing synthetic lycopene result in low all-E content, with E/Z isomer ratios of 3.4:1 to 3.8:1, failing to meet the specifications of biological lycopene extracted from natural sources like Blakeslea trispora, and existing thermal isomerization processes only increase all-E content to 73.4% to 87.8%.

Innovation Solution

Purification of C15-Wittig salts using a series of steps in aprotic solvents such as ethyl acetate, chloroform, and acetone, followed by a double Wittig reaction with C10-dialdehyde, allows for the production of lycopene with up to 95% all-E content or 97% 5Z content by controlling E/Z isomer ratios through solvent combinations and temperature adjustments.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional synthesis process is used to produce synthetic lycopene, then lycopene can be manufactured, but the all-E content is low (E/Z ratio of 3.4:1 to 3.8:1)

Engineering Contradiction:
Improveall-E contentVSAvoidsynthesis process complexity
Core Design Contradiction:
Manufacturing precisionVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by purifying all-trans-pseudoionone before synthesis to increase its content to 95-98%, and by pre-forming C15-Wittig salts with high all-E content (90-95%) through controlled reaction conditions. This preliminary purification and preparation eliminates the need for complex post-synthesis separation, directly achieving high all-E lycopene content while simplifying the overall manufacturing process.

Inventive Principle:
Principle #10Preliminary action

2Manufacturing precision

If all-trans-pseudoionone is separated from cis/trans mixture by fractional distillation, then higher all-E containing lycopene can be obtained, but the synthesis process becomes more complex

Engineering Contradiction:
Improveall-E contentVSAvoidpurification process complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent changes the purification parameter from fractional distillation to silica gel column chromatography, utilizing differential adsorption properties. By optimizing the eluent system (petroleum ether/ethyl acetate ratios) and column parameters, all-trans-pseudoionone is separated with 95-98% purity. This parameter change maintains high all-E content while simplifying the process compared to multiple distillation steps.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If C15 phosphonium salt is synthesized to produce lycopene, then lycopene can be manufactured, but the E isomer/Z isomer ratio decreases (only 65.2% to 71.1% all-E content)

Engineering Contradiction:
Improvelycopene productionVSAvoidE/Z isomer ratio
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The patent optimizes multiple reaction parameters: using purified all-trans-pseudoionone (95-98% purity) as starting material, controlling reaction temperature (0-25°C), selecting appropriate bases (n-BuLi, LDA), and optimizing solvent systems. These parameter changes ensure the C15-Wittig salt maintains 90-95% all-E content throughout synthesis, directly producing high all-E lycopene without requiring post-synthesis isomerization or extensive purification.

Inventive Principle:
Principle #35Parameter changes

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

The method achieves E/Z isomer ratios greater than 15:1 for all-E lycopene and less than 1:30 for 5Z lycopene, meeting or exceeding the specifications for biological lycopene, thereby producing synthetic lycopene with high all-E or 5Z content.

Implementation Method 1

Purification of C15-Wittig salts using a series of steps in aprotic solvents such as ethyl acetate, chloroform, and acetone

Methodology Applied
Scientific EffectSolubility difference: Solvation

Implementation Method 2

The method achieves E/Z isomer ratios greater than 15:1 for all-E lycopene and less than 1:30 for 5Z lycopene, meeting or exceeding the specifications for biological lycopene

Methodology Applied
Scientific EffectCrystallization: Crystallisation

Data Source

PatentEP2957565B1Methods for preparation of lycopenes from C-15 Wittig salts and methods for purification of high all-E containing and high 6Z containing C15-Wittig salts
Publication Date: 2018.03.07 ALLIED BIOTECH CORP

AI summary

The present invention relates to methods for preparation of lycopenes, especially to lycopenes with high all-E contents or high 6Z contents from C15-Wittig salts mixtures (with high all-E-contents and high 6Z-contents, respectively). C15-Wittig salts mixtures are purified and 6Z-C15-Wittig salts are extracted from the mixtures. The extracted 6Z-C 15-Wittig salts are used in the synthesis of lycopenes with high 6Z contents and the residues are used in the synthesis of lycopenes with high all-E contents.