NMR (Lake Nona)

Services

General synthesis of small molecule compounds

• Synthetic intermediates and specialty custom organic reagents
• Outsourcing for large scale or GMP synthesis
• Radioisotopic synthesis for pharmacological studies
• Acquisition, isolation and identification of Natural Products

Medicinal chemistry

• Evaluation of biological assay results (‘Hit Sets’) and assistance with next step decisions
• Synthesis of pharmacologically active reference compounds or positive controls
• Array and Library design and synthesis for ‘Lead Identification’
• Scaffold-based diversity libraries based on a structural theme
• Structure-Based Drug Design Synthesis of hypothesis and data driven Lead Optimization analogs based on iterative synthesis and assay
• Design, development, and synthesis of tagged, covalently modifying, and ‘pull-down’ probe molecules
• Design and synthesis on small molecule conjugated antigenic proteins for antibody development

Analytical chemistry

• 400 and 500 MHz NMR with 1 & 2D Spectra acquisition
• LC/MS purification and separations; MS accurate mass determination
• Chromatography: Normal phase, reverse phase and chiral separations on analytical and preparative scale.

Equipment and Resources

The Medicinal Chemistry core occupies approximately 3,200 sq. ft. of laboratory space and has four sixteen-foot hoods. The laboratory includes a Syrris AFRICA microfluidic synthesis system. This bench top system consists of two pump modules, a heater/cooler module, a pressurization module, a Gilson 203b fraction collection system, a product collection module, a reagent injection module, the FLLEX liquid-liquid extraction module, and a Gilson 222XL.

Dedicated analysis and purification instrumentation includes:

• a Waters automated preparative LC/MS AutoPurification system with both UV and MS based fraction collection and plate based or individual sample capacity
• a Shimadzu/API 2000 TQ LC/MS system coupled to a PDA and a Chemiluminescent Nitrogen Detector (CLND) for quantitative evaluation
• two Biotage SP4 Flashmaster chromatography units with multi-column functionality and a variable dual wavelength detector
• an Isco CombiFlash sq16x chromatography system
• five vacuum manifolds for multi-reaction SPE processing
• a Genevac EZ2 evaporation system

A 400 MHz Bruker Avance II NMR spectrometer with autosampler is located in a separate suite dedicated to the instrument. A 500 MHz Avance system with 3-channel Z-gradient broadband console and a 120 capacity autosampler is located in a separate suite dedicated to the instruments and the group.

Sample management equipment consists of a Mettler-Toledo Flexiweigh BA with embedded 1D and 2D barcode readers.

Dedicated synthesis equipment includes:

• a CEM 48 vial microwave system with an Explorer system for automated reaction processing
• Mettler-Toledo 24 and 48 well MiniBlocks with temperature jackets (6 pairs) including a six position shaker and a large recirculator for heating and cooling of up to 6 jackets
• a Thales-Nano H-Cube Continuous-flow Hydrogenation Reactor with a manual valve and injection system
• a Buchi R2 rotary evaporator for each chemist