The Milstein Synthetic Chemistry Core Facility was created through the generosity of Weill Cornell Overseer Howard P. Milstein. The facility provides the equipment and expertise to assist investigators in several areas. Utilizing a newly renovated organic synthesis laboratory, we have the capacity to design and execute efficient and economical chemical syntheses. Additionally, assistance in the purification and identification of unknown metabolites can be provided. The facility primarily serves Weill Cornell Medical College, but can occasionally extend its services to include the tri-institutional academic community.

The Synthetic Chemistry Core Facility is supported by the Howard and Abby Milstein Foundation medical philanthropy.

To learn more about its charity, please visit the Howard and Abby Milstein Foundation Web site.

Facilities

The Core Facility occupies 450 square feet and is supported by state-of-the-art resources. Standard benches are available for each scientist and include rotary evaporators with both low and high vacuum capacity, a fume hood with argon manifolds, and a Radleys StarFishTM multi-experiment workstation. In addition, the facility is equipped with a full array of chromatography and analytical equipment, including the following: Büchi Sepacore binary gradient low/high pressure silica gel chromatography system; Waters ACQUITY SQD Ultra Performance LC-MS with simultaneous PDA and mass detection (up to 2000 amu); Varian preparative HPLC utilizing two PrepStar SD-1 solvent delivery modules, PDA detector and fraction collector; Varian 4000 GC-MS and autosampler, capable of internal, external and hybrid ionization; Bruker TENSOR 27 series FT-IR spectrometer equipped with a Diamond ATR for fast and easy IR sampling; SRS OptiMelt automated melting point system; Varian INOVA 600 MHz NMR spectrometer.

Services

The core provides the following services:

• Consultation on experimental design and/or procedures, the availability of individual chemical compounds and/or reagents, and the feasibility of synthetic structures is available.
• Chemical synthesis of compounds that are not readily available.
• Synthesis of assay development tools and reagents including: fluorescently labeled compounds; affinity labeled compounds; cross linker-tethered molecules; labeled (13C, 2H, 15N) and radiolabeled (3H, 14C, 32P, 125I, etc.) compounds for preclinical and clinical pharmacological studies which cannot be directly addressed by the Radiochemistry Core facility.
• Synthesis of compounds in quantities that allow for in vitro and in vivo assays and secondary assays.
• Large-scale chemical synthesis of compounds with demonstrated biological activity in primary assays to provide material for further investigation.
• Structure-activity relationship (SAR) studies on validated pharmacophores in order to optimize targeting, specificity and bioavailability while minimizing toxicity.

Plan of Operation

1. Submission of Request: Investigators submit their request to the Core Facility director. Requests should include background information, and a brief statement concerning the nature of the project. After examination of the request to determine feasibility of the project and an estimated time of delivery, an initial consultation will be arranged. During this initial consultation, the Facility director will discuss the specific request in terms of its complexity and synthetic route, suggesting alternative routes when necessary. This will also establish a potential timeframe for synthesis and time of delivery, necessary when interfacing with other ongoing synthesis requests. The scheduling of each request takes the following into consideration:
   • The length of the synthetic sequence (i.e. number of steps)
   • Literature precedent
   • Scale of the synthesis
   • Investigational priority of the project within the core
2. Prioritization Committee: This is an internal oversight committee composed of Dr. Fred Maxfield, Dr. Carl Nathan, Dr. Harry Lander, and Dr. J David Warren. It is primarily concerned with the scientific merit of each project, prioritization, and scheduling of retained projects based upon the complexity of the synthesis and the timeframe needed by the user.


3. Synthesis: Following the recommendation of the Prioritization Committee, requested molecules would be analyzed in terms of the actual chemistry necessary for the project's ultimate success. Due to the extensive synthetic expertise currently in the Chemistry Core Facility, original synthetic methods may be developed so that the project can be completed in an efficient, timely, and cost-effective manner.


4. Delivery: Upon project completion, the compounds produced are delivered directly to the end user. Each compound will be supplied with a unique compound code, amount of compound synthesized, amount delivered, and delivery date. In addition, the complete spectral identity (NMR, IR, etc.) of each compound will be provided.


5. Development: Based upon biological test results, another consultation would be scheduled to assess the state of the project and to decide the optimal course of action. If further synthetic work is deemed necessary, this process could be reiterated.