Virtual Synthesis

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Scientific technical presentation Virtual
Synthesis - Reactor
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Elements of the Virtual Synthesis Technology

• Chemical properties predictions
• Calculator Plugins
• A language for describing chemical rules
• Chemical Terms
• A library of selective reactions knowing
  chemistry
• Chemaxon Reaction Library
• A reaction engine with high capacity and
  performance
• Reactor
• Virtual synthesis applications
• Synthesizer (combinatorial, random, exhaustive)

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Chemical Terms, a Language for Cheminformatics
Elements of the language

• structure matching functions (describing
  functional groups, reaction sites, similarity)
• property calculations (partial charge
  distribution, pKa, logP, localization energy)
• arithmetic and logic-operators

Chemical Terms examples
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Calculator Plugins
acceptor acceptorCount acceptorSiteCount
acidicpKa acidicpKaLargeModel aliphaticAtom
aliphaticAtomCount aliphaticBondCount
aliphaticRingCount angle aromaticAtom
aromaticAtomCount aromaticBondCount
aromaticElectrophilicityOrder aromaticNucleophilic
ityOrder aromaticRingCount array asymmetricAtom
asymmetricAtomCount atno atomCount
atomicPolarizability averagePolarizability
balabanIndex basicpKa basicpKaLargeModel BCUT
bond bondCount bondType canonicalResonant
canonicalTautomer carboaromaticRingCount
carboRingCount chainAtom chainAtomCount chainBond
chainBondCount charge chiralCenter
chiralCenterCount composition conformer
conformerCount conformers connected
connectedGraph connections count cxsmarts
cxsmiles cyclomaticNumber dihedral dissimilarity
distance distanceDegree donor donorCount
donorSiteCount dotDisconnectedFormula
doubleBondStereoisomer doubleBondStereoisomerCount
doubleBondStereoisomers dreidingEnergy
eccentricity electrophilicLocalizationEnergy
enumeration enumerationCount enumerations
exactMass field filter formalCharge formula
fusedAliphaticRingCount fusedAromaticRingCount
fusedRingCount hararyIndex hasValidConformer
hydrogenCount heavy heteroaromaticRingCount
heteroRingCount hyperWienerIndex isoelectricPoint
isotopeComposition isotopeFormula
largestAtomRingSize largestRingSize logD logP
logPIncrement logS logSMicro logSNeutral logSTrue
lowestEnergyConformer majorMicrospecies majorMs
map mass match matchCount max maxAtom maxValue
microspecies microspeciesCount microspeciesDistrib
ution min minAtom minValue molBinFormat
molecularPolarizability molFormat molImage name
nucleophilicLocalizationEnergy pair
piChargeDensity piEnergy piOrbitalElctronegativity
pKa plattIndex polarizability property
randicIndex refractivity refractivityIncrements
resonant resonantCount resonants ringAtom
ringAtomCount ringBond ringBondCount ringCount
ringCountOfAtom rotatableBond rotatableBondCount
shortestPath sigmaOrbitalElectronegativity
smallestAtomRingSize smallestRingSize smarts
smiles solubility solubilityAtIsoelectricPoint
solubilityOfMicroSpecies solubilityOfNeutral
solventAccessibleSurfaceArea sortAsc sortDesc
stereoisomer stereoisomerCount stereoisomers
stericEffectIndex stericHindrance sum szegedIndex
tautomer tautomerCount tautomers
tetrahedralStereoisomer tetrahedralStereoisomerCou
nt tetrahedralStereoisomers topologicalPolarSurfac
eArea totalChargeDensity traditionalName
uniqueSmiles valence vanDerWaalsSurfaceArea
wienerIndex wienerPolarity
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Applications of Chemical Terms
virtual synthesis reaction and synthesis rules
CT
pharmacophore analysis pharmacophore definitions
drug design goal functions
structure searching advanced query expressions
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Encoding Synthetic Knowledge in ReactionsThe
Friedel-Crafts acylation
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Encoding Synthetic Knowledge in ReactionsThe
Friedel-Crafts acylation generic scheme
The hydrogen of an aromatic carbon atom is
substituted with an acyl group of an acid halide
during hydrogen halide elimination.
C(a) aromatic carbon atom LO, S oxygen or
sulfur atom LCl, Br, I chlorine, bromine or
iodine atom
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Encoding Synthetic Knowledge in ReactionsThe
Friedel-Crafts acylation finding reactive sites
REACTIVITY charge(ratom(1), "aromaticsystem") lt
-0.2
Friedel-Crafts acylation occurs only if the
aromatic system is at least as activated as
monohalobenzenes.
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Encoding Synthetic Knowledge in ReactionsThe
Friedel-Crafts acylation finding the most
reactive sites
SELECTIVITY -energyE(ratom(1))
TOLERANCE 0.02
Directing rule the electrophilic substitution
takes place on the aromatic carbon atom with the
lowest localization energy having an attached
electrophile in the transition state. Aromatic
carbons having the lowest localization energies
provide the main product. Aromatic carbons
having similar localization energies to the
lowest one (within 0.02 tolerance range) are
included.
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Encoding Synthetic Knowledge in ReactionsThe
Friedel-Crafts acylation excluding compounds
giving side reactions, destroying the catalyst
EXCLUDE match(reactant(1), "Cl,Br,IC(O,S)CC
") or match(reactant(0), "HO,SCO,S")
or match(reactant(0), "PH")
or (max(pka(reactant(0), filter(reactant(0),
"match('O,SH1')"), "acidic")) gt 14.5)
or (max(pka(reactant(0), filter(reactant(0), "
match('71H', 1)"), "basic")) gt 0)
Exclude aromatic compounds containing
nucleophilic groups and acrylic halides. For
example, phenols and indols are processed, but
benzylalcohols or anilines are not.
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Encoding Synthetic Knowledge in ReactionsThe
Friedel-Crafts acylation as a smart reaction
REACTIVITY charge(ratom(1), "aromaticsystem") lt
-0.2
SELECTIVITY -energyE(ratom(1))
TOLERANCE 0.02
EXCLUDE match(reactant(1), "Cl,Br,IC(O,S)CC
") or match(reactant(0), "HO,SCO,S")
or match(reactant(0), "PH")
or (max(pka(reactant(0), filter(reactant(0),
"match('O,SH1')"), "acidic")) gt 14.5)
or (max(pka(reactant(0), filter(reactant(0), "ma
tch('71H', 1)"), "basic")) gt 0
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Reactor, the engine
ChemAxon Reaction Library
Baeyer-Villiger ketone oxidation Baylis-Hillman
vinyl alkylation Beckmann rearrangement Bischler-N
apieralski isoquinoline synthesis Friedel-Crafts
reaction Friedlander quinoline synthesis Gabriel
synthesis Grignard reaction Hell-Volhardt-Zelinski
halogenation
REACTOR
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Reactor the Application
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The Reaction Editor
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Reactor, key features

• Effective
• millions of compounds in a combinatorial reaction
• up to 500,000 compounds / hour (P4 1.8 GHz)
• Compatible
• reactions MRV, RXN, RDF, SMARTS/SMIRKS
• compounds MRV, MOL, SDF, SMILES
• mapping MDL, Daylight, automapper
• Flexible
• memory, file and database operations (via Oracle
  Cartridge)
• sequential or combinatorial mode
• compound or reaction output type
• reverse direction
• Smart
• chemo-, regio- and stereospecific
• customizable
• Available
• Java API, command line tool, JSP, GUI
• premade reaction library
• documentation and examples

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