The development of phosphate tethers for small molecule synthesis has revealed their use as removable, functionally active tethers that are fundamentally different from widely used silicon-based variants. These
tethers are capable of multipodal coupling and multivalent activation and serve as latent leaving groups in selective cleavage reactions. Application of this method to the synthesis of a number of bioactive compounds is reported and will highlight the versatile nature of this tether for small molecule synthesis.
The rapid access to collections of diverse molecules in desirable quantities and purity for high-throughput screening is an important challenge in drug discovery. In this regard, methods that integrate synthesis and purification have become powerful tools in the arena of facilitated synthesis. A second feature of this talk will focus on the production of a number of ROMP-derived high-load, phosphorus-based oligomers with tunable properties for use in the production of sultam libraries.
(1) Waetzig, J. D.; Hanson, P. R. A Multifaceted Phosphate Tether: Application to the C1-C14 Subunit of Dolabelides A-D. Org. Lett. 2008, 10, 109-112.
(2) Whitehead, A.; Waetzig, J. D.; Thomas, C. D.; Hanson, P. R. A Multifaceted Phosphate Tether: Application to the C15-C30 Subunit of Dolabelides A-D. Org. Lett. 2008, 10, 1421-1424.
(3) Thomas, C. D.; McParland, J. P.; Hanson, P. R. Divalent and Multivalent Activation in Phosphate Triesters: A Versatile Method for the Synthesis of Advanced Polyol Syntons. Eur. J. Org. Chem. 2009, 5487-5500.
(4) Thomas, C. D.; Hanson, P. R. Phosphorus and Sulfur Heterocycles via Ring-Closing Metathesis: Application in Natural Product Synthesis. Metathesis in Natural Product Synthesis. (J. Cossy, C. Meyer, Eds), Wiley-VCH: Weinheim, Germany, 2010.
(5) Venukadasula, P. K. M.; Chegondi, R.; Maitra, S.; Hanson, P. R. A Concise, Phosphate-Mediated Approach to the Total Synthesis of (–)-Tetrahydrolipstatin. Org. Lett. 2010, 12, 1556-1559.
(6) Long, T. R.; Maity, P. K.; Samarakoon T. B.; Hanson P. R. ROMP-Derived Oligomeric Phosphates for Application in Facile Benzylation. Org. Lett. 2010, 12, 2904-2907. NIHMS211406 (PMC in Progress).
(7) Ullah, F.; Samarakoon, T. B.; Rolfe, A.; Kurtz, R. D.; Hanson, P. R.; Organ, M. G. Scaling Out by Microwave-Assisted, Continuous Flow Organic Synthesis (MACOS): Multi-Gram Synthesis of Bromoand
Fluoro-benzofusedsultams Benzthiaoxazepine-1,1-dioxides. Chem. Eur J. 2010, In Press.
(8) Schätz, A.; Long, T. R.; Grass, R. N.; Stark, W. J.; Hanson, P. R.; Reiser, O. Immobilization on a Nanomagnetic Co/C Surface using ROM Polymerization: Generation of a Novel Hybrid Material as Support for a Recyclable Palladium Catalyst. Adv. Func. Mat. 2010, In Press.
(9) Maity, P. K.; Rolfe, A.; Samarakoon, T. B.; Faisal, S.; Kurtz, R. D.; Long, T. R.; Schatz, A.; Flynn, D. L.; Grass, R. N.; Stark, W. J.; Reiser, O.; Hanson, P. R. Monomer-on-Monomer (MoM) Mitsunobu Reaction: Facile Purification Utilizing Surface-Initiated Sequestration. Org. Lett. 2011, 13, 4-7.
NIHMS255853 (PMC in Progress)
(10) Rolfe, A.; Loh, J. K.; Maity, P. M.; Hanson, P. R. High-Load, Hybrid Si-ROMP Reagents. Org. Lett. 2011, 13, 8-10. NIHMS255850 (PMC in Progress)