Reaction searching workshop LEO PHARMA, Brnehaven 2006

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Reactions in SciFinder
Reaction searching workshop LEO PHARMA,
Børnehaven 2006
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Unique and comprehensive databases

• CASreact 10 million Reactions, 1840
• CAplus - Bibliographic - 25 million references,
  abstracts, citations, 1907
• Registry - Substances 26 million substances and
  56 million sequences
• Chemcats - Chemical catalogs online - 900
  catalogs 8,6 million compounds
• Chemlist - Chemical inventories 226.000
  regulated chemicals
• Medline - Bibliographic - 13 million references,
  1958 -

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Unique and comprehensive databases Creating
Content
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CASreact

• A true organic, multible step, chemical reaction
  database
• Benefits Reaction conditions, yields, catalysts,
  solvents, multible steps, retro-synthesis link,
  functional group transformation searchable with
  reaction roles (also non-reacting). Analyze on
  yield, solvents, etc.
• ShortcomingsNo stereosearch, No properties,
  Limited catalyst searching.

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CAplus

• Bibliographic
• Benefits Consistent key word searching in
  patent- and journal references.
• CASroles context keywords accociated with
  substances or groups of compounds.
• ShortcomingsReaction papers not indexed with
  conditions, yields or solvents.

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CAS Roles - a selection

• PREP/RL - Assigned to a substance in studies of
  the synthesis of the substance as a distinct
  chemical entity, formed with preparative intent,
  via a chemical, biochemical, or nuclear reaction.
  The recovery, purification, separation, or other
  intentional formation with preparative intent of
  a desired substance also receives a PREP role.
• RCT/RL Assigned to substances at participates in
  a discrete preparative chemical reaction and
  contribute to the molecular structure of the
  product. Assigned to reactants in discrete
  chemical reactions where the product substance is
  not necessarily identified, reactants in failed
  reactions, and reactants in atomic number or mass
  in nuclear reactions. Indexable intermediates
  that are prepared and further reacted receive
  both the RCT role and the appropriate specific
  PREP role.
• CAT/RL Assigned to a substance where there is a
  demonstrated, claimed, or clearly intended use as
  a promoter, initiator, or functional equivalent
  in any reactions or processes on a lab or
  commercial scale. Catalyst supports, catalyst
  promoters, and catalyst additives are considered
  to be part of the overall catalyst system and
  receive the CAT role. Enzymes used in
  preparative biosyntheses and negative catalysts
  and other reaction inhibitors also receive this
  role.

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CAS Registry

• Substance database
• Benefits Biggest collection of substances.
  Structure searchable, properties searchable,
  stereo search, tautomeric searching, metal
  searching, name searcing, similarity searching.
• Refine and analyze on a search set.
• ShortcomingsNo reaction details.

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CHEMCATS

• Commercial substances
• Benefits Biggest collection of commercial
  avaible substances. Direct linkable from Registry
  or CASreact.
• Shortcomings Not prices from all vendors.

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• And NOW The Questions

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Similar Catalysts
The Stille Coupling is catalyzed commenly with
Tetrakis(triphenylphosphine)palladium. Find
simmilar palladium catalysts for the Stille
Coupling
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Medicinal chemistry Synthetic papers
Find all relevant preparations for
Pholcodine.First Try Substance identifier and
use the PREP role. Then Try exact search Tip
Try copy and paste !!

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A name reaction Try the functional group search!

• Find conversions from Aldehydes to Ketones
• Especially those where a Dithiol is used as
  reagent (The Seebach-Corey method)
• Select reactions prepared combinatorial.
• Identify original paper from Seebach/Corey

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Non-reacting groups
The Wittig reaction involves a transformation of
an aldehyde or ketone to an alkene. Search the
special example where also a carboxylic ester is
present through out the reaction
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One good paper!

• Find paper(s) where the following species acts in
  an addition reaction with unsatuated ketones.
• Use Get related to find similar papers leading
  to other tertiary Zn containing compounds in
  similar reactions

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Stereo conversions
Find stereo selective reactions going from S
stereo isomer of 3-hydroxy steroids to the R
stereo isomer.
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Heck reactions

• You are interested in Heck reactions but only
  those where the aryl halide is simple (less MW
  than 220) and the starting material is
  commercial.
• Use Registry to locate the smaller compounds and
  CASreact to find the synthetic route.
• Limit to higher yields than 80

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Poison-dart frog Aza compounds - Retrosynthesis

• Poison dart frogs are a rich source of
  stereospecific compounds. Find piperidinyl like
  compounds originating from Dendrobates frogs. See
  the structure below for stereospecific structure.
• Show routes for the total synthesis of selected
  compounds which are actually isolated from
  Dendrobates.

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Challenges in Chemical Industry

• New inventions
• Patent protection
• Cheap production
• Commercial starting materials
• Few steps, high yeils
• Legal demands
• REACH

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New in SciFinder 2006

• Structure Similarity Searching
• New structure and reaction query tools Variable
  Attachment Position tool and Repeating Group tool
  
• Easy access to additional reaction information
• Enhanced multi-step reaction display
• New quick look-up of research references
• Duplicate removal (Medline - CAplus)