Retrosynthetic analysis

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set up environment

source /nfs/soft/dock/DOCK37/env.csh
source /nfs/soft/www/apps/zinc15/envs/internal/env.csh

run program

zinc-manage -e shell  utils retrosynth analyze --smiles="Cc3ccn2nc(CCCC(=O)Nc1ccc(O)cc1C)cc2c3" --recursions=0 --show=successful

sample output and explanation

Line-1 (1 options)
	Successful Synthesis via negishi coupling in 1 steps
		Cc1ccn2nc(CCl)cc2c1 . Cc1cc(O)ccc1NC(=O)CCCl >> Cc1ccn2nc(CCCC(=O)Nc3ccc(O)cc3C)cc2c1
		Reactant 1: Cc1ccn2nc(CCl)cc2c1 - Purchasable as ZINC000238540793
		Reactant 2: Cc1cc(O)ccc1NC(=O)CCCl - Purchasable as ZINC000041725839

If you want a bit more diversity you could change --show to partial to get reactions where less than all (but more than none) of the reactants were available. This also may be useful if you want to use a different reaction. You can the either run similarity searches around the unresolved reactants or try to increase the --recursions to try a few more steps... That can get out of hand above 2 or 3 though (not that you'd want to do that).

step 2 - Gets ZINC IDS

  • 1) ZINC000238540793
  • 2) ZINC000041725839

I then ran a similarity search for building block compounds containing the reactive group for the left and right side of a Negishi coupling (no easy interface available for this yet)

These are left.smi and right.sim in /nfs/work/teague/MK/

These current results are at 70% Tanimoto because I misplaced the 50% Tanimoto downloads (doh!)

step 3

I then ran the reactor in DOCK37 ($DOCKBASE/ligand/reactor/react.py) with the RXN SMARTS for the Negishi coupling ( "[#6:1]-,:[#17,#35,#53].[#6:2]-[#17,#35,#53]>>[#6:1]-[#6:2]" ) and the left.smi and right.smi and filtered for duplicates. This creates synthetic.smi. Modify that to be better suited for db2 generation.

(all in the run.sh script in that directory).

step 4

Run database building using the DOCK37 pipeline.

$DOCKBASE/ligand/generate/build_smiles_ligand.sh database.smi


For the new compound you showed me, I think we need to investigate the reactions and see which one is failing to validate.

I am building the db2 files now in that directory.