Synthetic Chemistry

During its 25 years’ history, ChemDiv has developed an arsenal of proprietary approaches towards fast, tractable and, even more importantly, novel chemistries. Examples include cascade addition-cyclization, multi-component reactions, one-pot syntheses, assemblies of macrolide-mimetics, spiro– medium- and large(macro) heterocyclic systems, isosteric replacements of aminoacids, di-/tri-peptides and many other unique protocols. Our teams of highly skilled scientists have formidable experience in addressing your synthetic, medicinal, building blocks, medicinal chemistry and compound optimization needs. It is this combination of a robust science, drug discovery expertise and transparent business/financial models that allowed us to offer Chemistry Systems on Demand™ approach. Specifically, we provide you with a set of our validated chemistries and respective scaffolds for your assessment followed by synthesis of large or small (target/purpose-focused) custom compound selections. Alternatively, we are happy to accommodate your chemical development ideas in order to convert them into libraries that uniquely suit your project needs.

CUSTOM SYNTHESIS

Several notable advantages offered by our synthetic team include:

  • Fast turn-around time in assessing project feasibility, cost and timing;
  • Management of a project by both science and business-focused professionals;
  • Development of your proprietary chemistries or library design based on our proprietary templates;
  • Estimated 10,000 scaffolds to choose from
  • Synthetic, scale-up or medicinal chemistry and target considerations for design
  • Computational and modeling assessment of target relevance, drug-/lead-like character
  • Implementation of your custom selection criteria and filters
  • Flexible library format: 20-500 analogs/scaffold, diverse plating and delivery capabilities/logistics;
  • Proprietary collection of ca. 4,000 building blocks
  • Development and transfer of protocols and key intermediates
  • Material(s) delivery on a 1 mg to 10 kg scale
  • Custom plating, solution or dry film formats
  • Purification to your specifications
  • High-throughput H-NMR, LC/MS and HPLC-based purification if needed

EXPERTISE

  • Heterocyclic chemistry
    • Aromatic and unsaturated heterocycles
    • Natural products and natural-like systems including optically active compounds
    • Heterocyclic systems with improved solubility and stability
    • Macrolides and their analogues
    • Medium- and large ring systems with calculated drug-like properties
    • ‘Topologically’ rigid compounds including spiro- and bridged heterocycles
    • High ‘unsaturation’ (Fsp3) content on demand
  • Modern techniques
    • Organometallic chemistry: Suzuki, Sonogashira, Heck, Grubbs, Buchwald; large scale Li, Mg, Zn, Cu, Au – mediated reactions, etc.
    • Enantioselective assembly including catalysis;
    • Medium-/large-ring systems assembly including template-guided multi-component reactions, nucleophilic aromatic substitution, metathesis and others;
    • Cascade addition, cycloaddition, multi-component cyclization(s);
    • Microwave-assisted synthesis, both liquid and solid phase;
    • Green chemistry;
    • Liquid crystals;
    • High throughput analysis (LCMS, HPLC, multi-nuclear NMR)
    • High throughput purification (HPLC, mass-directed HPLC, SPE, UV FPLC)
  • Solid support chemistry
    • 10-10,000 compound parallel synthesis
    • Solid-phase catalysts, scavenger resins
    • Gram scale solid phase synthesis
  • Optically active materials
    • Asymmetric synthesis
    • Enantiomers and diastereomers: synthesis, separation and identification
    • Analysis and purification (chiral HPLC, optical rotation, LSR)
    • Absolute and relative stereochemistry assignment (X-ray)
    • Peptidomimetics and unnatural amino acids and derivatives
  • Special conditions
    • High pressure reactions (up to 200 bar)
    • Large scale hydrogenation
    • Large scale reactions (up to 30 L)
    • Large scale purification
  • Scale up

SYNTHETIC PATHWAYS DESIGN

Multiple considerations go into the design of templates, libraries and unique molecules. Naturally, ChemDiv takes into consideration and implements every specific consideration of our Clients. Additionally, key guidelines of modern drug-discovery including both chemical and biological aspects are involved:

  • Template/compound novelty, and intellectual property status;
  • Drug- or lead-likeness, including lipophilicity, biomembrane/blood-brain barrier permeability, Fsp3 character, ligand efficiency vs. lipophilic ligand efficiency and (yes!) water solubility
  • Relevance to specific Biological goals, for example targets, target classes, pathways, and cellular processes
  • Diversity as compared to the developed commercial chemical space or pertinent to your specific needs
  • Synthetic considerations: feasibility, building blocks (commercial and/or project and library specific, including your proprietary selection)
  • Rapid expansion to launch structure-activity relationship (SAR) studies of representative molecules

At ChemDiv, we are always ready to incorporate your specific needs into every step of the design process.

SYNTHETIC PATHWAYS VALIDATION

Every chemical procedure is as good as its validation. At ChemDiv, we pay specific attention to this crucial step of chemical discovery. Once the protocol is suggested and adopted, our team of chemists evaluates reagents, conditions, feasibility, scaleability and safety in a multi-parameter validation matrix. If desired, our clients may be closely involved in either contributing to or monitoring of this process. In general, validation takes 2-4 weeks in order to gain information with regard to:

  1. The general utility of the protocol or synthetic access to the molecule of interest
  2. Tentative yield(s)
  3. Feasible synthetic route(s) and potential for further detailed optimization(s)
  4. Alternative strategies aimed at improving:
    • Synthetic feasibility
    • Yield(s) of the targeted materials
    • Financial/material aspects of the work
  5. Potential to expand the procedure in order to conduct multiple compound, library/ies and/or structure-activity relationship (SAR) studies

As a rule of thumb, during the validation stage of larger compound sets corresponding to a specific template (>50-100 compounds), our team validates at least 10-20% of the chemical space to make our partners confident with regard to the anticipated outcome of larger studies.

Please contact our team at [email protected] to discuss your specific needs and application.