This document discusses using Wiley's Chemistry Toolkit to plan syntheses of target molecules. It describes an approach using computer-aided synthesis design (CASD) to perform retrosynthetic analysis back to available starting materials, generating many alternatives and supporting them with literature examples. CASD works by extracting reaction rules from source reactions in databases like CIRX and applying chemical perception to identify compatible functional groups and regio- and stereoselectivity. The goal is to provide an integrated solution for data mining and synthesis planning.

1. Synthesis Planning With Wiley’s Chemistry Toolkit
Orr Ravitz
wileysciencesolutions.com

2. The Vision
Turn:
information into knowledge,
answers for questions into solutions for problems

3. How can I make my target molecule:
Quickly
Efficiently
Cheaply
From building blocks available in batch quantities
Using scalable methods (techniques, conditions…)
With low environmental footprint
How can I make a series of compounds?
Synthesis Challenges
Discovery
Development
Process

4. Knowledge
Intuition
Experience
How do we approach the problem now?
Standard literature mining:
Has this been made before?
Any similar structures?
How can I accomplish this transformation that I have in mind?
Step-by-step analysis

5. Computer-Aided Synthesis Design
The Approach:
Comprehensive rule- and precedent-based retrosynthetic analysis back to available starting materials.
Automated rule generation with manual rule curation.
Generate many alternatives.
Provide supporting literature examples.
Allow user guidance and control.

6. Rule Extraction
Source reactions
Esterification examples
Other examples
··· → ···
··· → ···
··· → ···
Esterification rule
Other rule
··· → ···
Reactions
Reaction Rules

7. Chemical Perception
Identify essential chemical environment and compatible functional groups
?
?
?
Regioselectivity
Stereochemistry

8. Synthetic Routes

9. Alternative Paths

10. Literature Examples

13. CIRX and CASD
Detail:
Chemoselectivity (including 0% yield reactions)
Stereochemistry:
Stereodescriptors, (+)-I, (±)-I, (R)-I, (S)-(-)-I
Selectivity: e.e., d.e. ds and also E:Z>95:5, α:β=1:3
Labelling of asymmetrical centers (R,S)
Meta data: conditions, solvents, catalysts, bibliography
Accuracy and consistency:
Mapping
Attention to details
Very high quality assurance
Uniformly across DB

14. An Integrated Solution
Data mining and synthesis planning in one tool.
Use the most suitable data source for predictions (CIRX)
Develop the data source to address the needs of the chemists
Offer a gateway to the users’ own data fully behind the firewall.
Integrate/ interact with other data sources
Interact with other tools
Use the system to generate and share knowledge
Become involved!