3. The Motivation
Goal:
Synthesize quickly, efficiently, economically, ecologically.
Intuition
Knowledge
Experience
Literature
Data:
- 1000’s of high utility synthetic methods
- 100,000’s of building blocks
The value of a good idea:
Faster R&D turnaround – remain ahead of the curve
Synthetic efficiency – lower development, production costs
Better use of human time – increased productivity
4. Chemical data have been used in the same manner for over 100 years!
Synthetic plan Thought
process
There is more than one way to synthesize
a compound. Little in current approaches
assists in finding the better ones.
• Non-linear
• Highly biased
• Driven by intuition and knowledge
• Gaps filled using literature searches
5. What is a synthetic idea?
A full synthetic route, a key step, a critical sequence of reactions
Not necessarily in your “comfort zone”
Utilizing starting materials efficiently
No obvious published precedent
6. Why Computer-Aided
Synthesis Design?
Cover more options, miss less opportunities
Chemist
Creativity
Intuition
Strategic perspective
Knowledge (what
works, what doesn’t)
Computer
Thoroughness
Lack of bias
Speed
Low cost
7. 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.
9. Reactions
Reaction Rules
Reaction Perception
Source reaction:
Extracted core
Extended core
Reaction file with atom mapping
Atoms attached to bonds changed, made or broken in the reaction
Include all structural motifs that are essential for the reaction to occur
10. Rule Extraction
Similar extended cores
Completed reaction rule
Common extracted core
Nucleofuge (NF) -
a leaving group which
carries away the bonding
electron pair.
Generalized rule
Generalized group (NF) is
replaced by the most
common group.
Reactions
Reaction Rules
13. Limitations Associated with
Small Reaction Source
Methods in Organic Synthesis (MOS) – 44,000 mapped reactions.
• Partial coverage of synthetic methods
• Small clusters – higher risk of over- and under-constrained rules
• Not enough statistical power for supplementary information – yield,
regioselectivity
• Too few examples to determine functional group tolerance
• Exact matches are rare
Larger databases are available, but not as part of CDS:
• Reaxys - Elsevier
• ChemInform (CIRX) – Wiley & Sons
14. Solutions Ranking
Prioritization of the alternatives – show best solutions first
Transforms merit is evaluated using:
• Reduction of target complexity (simplifying transforms before FGI/FGA).
• Minimize wastage (atom efficient reactions).
• Starting material coverage.
• Prefer thoroughly explored chemistry (based on example count) .
• Penalty for interference.
• Yield.
16. Quota System
• Each institution is assigned a search quota
• Registration is open only when searches are available
• For registered users – new search page deactivated when
quota is filled
• Old searches remain accessible even when quota is filled
17. ARChem – Synthesizing Ideas
Bringing Computational Power to Organic Synthesis
SimBioSys Inc.
Thank you!
For more information:
Orr Ravitz, Ph.D.
ravitz@simbiosys.com
+1 (416) 741-4263
18. ARChem
Transforming data into Knowledge. Generating ideas.
Reactions Reaction
Rules
Starting
Materials
High Level
Reasoning
examples methods
Reaction mechanisms
Synthetic strategies
Search strategies
Solutions ranking
Methods
in Organic
Synthesis
