Library Synthesis
Rapid access to high-quality compound libraries plays a crucial role in accelerating drug discovery processes. Enamine has established itself as a prominent leader in library synthesis, producing over 300 000 individual purified compounds annually in substantial quantities, available as dry samples. Our expertise enables us to deliver efficient library synthesis services with quick turnaround times. Our competitive advantages stem from the following:
- The world’s largest stock of building blocks. With a staggering inventory of 300 000 building blocks available in our own stock, we have an unparalleled resource to immediately commence the synthesis project and create compound libraries of exceptional quality, boasting an extensive array of designs, novelty, and innovative structural motifs
- Knowledge of the building block reactivity. To optimize efficiency and conserve valuable scaffold material, we leverage our internal statistical data to avoid undertaking dubious syntheses that are prone to failure. This data-driven approach allows us to make informed decisions, avoiding wasteful processes and ensuring that our resources are allocated effectively
- Unprecedented capabilities in parallel synthesis. Our unmatched expertise in parallel synthesis, backed by 180+ validated protocols, enables the rapid production of over 1 500 compounds per day.
Project types
If you have HTS hits, we can swiftly search for their synthesis analogs in our REAL Database/Space. Alternatively, we can design a library of analogues using a systematic medicinal chemistry approach. Our deep understanding of our building block collection allows us to propose unique scaffold-hopping strategies, intriguing bioisosteric replacements, or suitable decorators to meet desired patentability and physicochemical profile requirements.
We provide two options for synthesizing your compound library. We can start from scratch, beginning with scaffold synthesis. Alternatively, if you already have the scaffold synthesized, you can provide it to us, and we will leverage it to synthesize a compound library of the desired size.
With our vast building block inventory and expertise in library synthesis, we can rapidly synthesize diverse compounds to expand your collection. Originating from our design, e.g., REAL Database / Space, or your collaborative input, these high-quality compounds will address specific targets, enhance structural diversity, or replenish depleted compounds.
We specialize in designing and producing customized compound libraries. Our expertise includes incorporating specific recognition motifs like PROTACs, as well as linkers and warheads such as covalent binders. Whether you need small or large libraries, we can tailor them to your specific requirements.
This is a widely employed approach in library synthesis, where the scaffold compound is either synthesized internally or obtained from another CRO and provided then to Enamine for parallel synthesis. You have the flexibility to choose building blocks from our catalog or select target compounds from a virtual compound library that we can enumerate based on our knowledge of building block reactivity. With our comprehensive statistical data, we can maximize the number of compounds synthesized using a limited amount of scaffold material. Once you send the scaffold to our EU- and US-based offices, we will swiftly return a compound library in the most suitable plate/vial format for rapid testing. Our scaffold decoration service is available on a fixed-price basis or can be arranged within the framework of FTE collaborations, providing customized solutions to suit your specific requirements.
The chemistry we perform
We enable parallel synthesis through a repertoire of over 35 validated reactions in numerous variations affording 160+ combinatorial synthesis protocols. In certain cases, we can also perform these reactions in a consecutive one-pot manner, spanning 2-3 steps:
- All standard transformations (amidation, alkylation, arylation, reductive amination, etc.),
- Post-reaction protective group removal (Boc-, t-Bu, MOM, THP, etc.),
- Transition metal-catalyzed reactions (Suzuki, Stille, Buchwald-Hartwig, etc.),
- Ring closures (1,2,4- and 1,2,3-triazoles, 1,2,4- and 1,3,4-oxadiazoles, thiazoles, imidazoles, etc.),
- Photoredox-catalyzed alkyl-aryl coupling reactions.
We have a wealth of experience in custom synthesis of scaffolds and various intermediates and can offer a full cycle of library synthesis starting from scratch.
Quality control and logistics
We perform reversed-phase preparative HPLC purification on all synthesized compounds to ensure they meet purity requirements (usually 90% or 95% pure). Their quality is controlled with LCMS and up to 100% with 1H NMR. The compounds can be delivered in virtually any containers, including those received from a customer and assay-ready plates for immediate screening.
