Reprint f rom Molecular Connect ion Vol 24 No 1 2006

Case Study

Protein kinase C (PKC) is a target of greatinterest in the development of antitumoragents because of its crucial role in cellularsignal transduction and tumor promotion.Derivatives of decursin are novel cancerchemotherapeutic candidates isolated fromAngelica gigas Nakai. Initial studies showedthat decursin exhibits PKC-activatingactivity, suggesting that its cytotoxicitymay be related to the PKC activation.

Step 1. For our study, we want to synthesize derivatives of decursin withvarious R groups in order to studybioactivity of the derivatives.

Step 2. A search for the heterocyclicscaffold in MDL synthetic methodologydatabases retrieves a reaction of interest(Figure 2).

Step 3. If an efficient synthetic schemecan be built on this reaction, it will providea route to the target compounds, as theproduct of this reaction has key functionalityat the point of R-group variation. Clickon Details to see comprehensive information concerning this reaction(Figure 3).

Synthesize or buy?Unlocking the power of DiscoveryGate®

efore synthetic chemists replicate reactions or create compounds, they mustdetermine whether the materials or precursors they need are already available—or if they must be synthesized.

For scientists who look for compounds or reactions using the DiscoveryGate® contentservice, determining whether products or constituents of a reaction are commerciallyavailable is simple.

“Data sources on DiscoveryGate are indexed,” says Craig Morgan, Product Managerfor MDL® Available Chemicals Directory. “This allows synthetic chemists to quicklydetermine whether a chosen synthesis is cost-justified or prohibitive. Access to the primaryliterature and associated Material Safety Data Sheets (MSDS) provides information ondetermining factors such as yields and safety. Direct links to Available ChemicalsDirectory provides comprehensive sourcing information.”

With DiscoveryGate, synthetic chemists can quickly access information on methods,safety, chemical availability and pricing. “In many cases there is no need to synthesize whenyou can buy,” says Morgan. “However, if synthesis is necessary, DiscoveryGate providesimmediate access to the primary literature and associated retrosynthetic schemes.”

The following example shows how the indexed power of DiscoveryGate can speeddecision-making.

Figure 1: The antitumor agent decursin

B

Figure 2: Relevant reaction retrieved from ChemInform Reaction Library (FIZ CHEMIE)

Figure 3: Drilling down to further reaction details, expanding the search with “Also found in” links

With DiscoveryGate,

synthetic chemists can

quickly access information

on methods, safety, chemical

availability and pricing.

Step 4. By clicking on ACD in the “Alsofound in” links, we find that one of the nec-essary reactants is available from severalsuppliers. By clicking on OHS MSDS, wefind that there is an associated MSDS for thereaction catalyst, zinc chloride (Figure 4).

Step 5. Next we need to find methods forpreparing the other reactant. Click Returnto Synthetic Methodology Informationand Return to Search Results. From here,click Synthesize Reactants to display theretrosynthetic schemes (Figure 5). Thisidentifies methods for preparing reactantsthat are not commercially available.

“The retrosynthetic scheme display enableschemists to quickly and efficiently determinethe suitability of a synthetic route to targetmolecules,” says Terry Wright, SeniorProduct Manager for MDL SyntheticMethodology Products. “Retrosyntheticschemes also provide a behind-the-scenessearch for potential starting materials fromreaction records.”

Step 6. Click on Details in the retrosyntheticscheme display to see more detailedinformation on the applicable reaction(Figure 6). On this page, you can see if thereaction components are commerciallyavailable by selecting Use as Query.

Step 7. You can also examine an originaljournal article by clicking on the referencehyperlink on this page1. This provides additional experimental details about thereaction (Figure 7).

The preceding workflow illustrates theuse of DiscoveryGate and its “Also foundin” hyperlinks to quickly determine whetherreactants, catalysts, solvents or productsfor a given reaction are commercially available. If they are not obtainable, retrosyn-thetic schemes offer an alternative route fordetermining if they can be synthesized fromreadily available compounds.

For more information on finding the information you need with DiscoveryGate,contact your Elsevier MDL AccountManager or submit a request for informationat www.mdl.com.

Figure 4: Rapid access to sourcing details from several suppliers and useful MSDS data

Figure 5: The value of the retrosynthetic scheme in synthesis planning

Figure 6: Exploring further reaction details for the precursor reactions in the scheme

Figure 7: Article abstract as displayed in Elsevier’s ScienceDirect and full article retrieved fromTetrahedron Letters (Pergamon)

1Access to and use of certain third-party contentrequires DiscoveryGate subscribers to secure suchrights directly from the content provider.

Reprint f rom Molecular Connect ion Vol 24 No 1 2006

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