Vince Lactam
edit(±)-2-Azabicyclo[2.2.1]hept-5-en-3-one
editVince lactam is the commercial name given to the bicyclic gamma-lactam 2-azabicyclo[2.2.1]hept-5-en-3-one. This lactam is considered one of the most versatile and useful molecules in organic and medicinal chemistry and has the unique distinction of being used as a synthetic precursor for three drugs (approved or in clinical trials).[1] It is named after Prof. Robert Vince (Director, Center for Drug Design, University of Minnesota) who was the first person to utilize the unique structural features of this molecule for the preparation of a highly significant class of therapeutic compounds known as carbocyclic nucleosides.[2] Dr. Vince's work with this lactam eventually led to his another ground-breaking contribution to science in the form of blockbuster HIV drug Abacavir (commercially available as ZiagenTM).[3] Vince lactam has been extensively used for the preparation of various carbocyclic nucleosides with medicinal applications in mind, including carbocyclic Puromycin (I)[4], carbocyclic Ara-A (II)[5], carbovir (III)[6] and guanine as well as azaguanine carbocyclic derivatives (IV)[7]
The development of Vince lactam as a versatile synthetic precursor and a useful intermediate has led to it's use in the development of various different nucleoside analogs such as difluoro guanosine derivatives (V)[8], carbocyclic oxanosine and related derivatives (VI)[9], and precursors for azidocarbonucleosides (VII)[10]. The lactam has found several applications in targeting an array of different diseased conditions by providing various non-nucleoside therapeutic molecules as well. Some well known examples include scaffolds for the preparation of glycosidase inhibitors (VIII)[11] and GABA-AT inhibitors (IX)[12].
(±)-2-Azabicyclo[2.2.1]hept-5-en-3-one is commercially available as Vince Lactam from several vendors throughout the world.
References
edit- ^ (a) http://pubs.acs.org/cen/coverstory/8128/8128finechemicals1a.html (b) Holt-Tiffin, K. E. Chimica Oggi 2009, 27, 23-25.
- ^ http://www.cdd.umn.edu/directory/vince/home.html
- ^ (a) Daluge, S.; Vince, R. J. Org. Chem. 1978, 43, 2311-2320. (b) Vince, R.; Hua, M. "Synthesis of carbovir and abacavir from a carbocyclic precursor" Current protocols in nucleic acid chemistry Ed. Beaucage, S. L. 2006, Chapter 14 Unit 14.4. DOI: 10.1002/0471142700.nc1404s25'. (c) Vince, R. "A brief history of the development of Ziagen" Chemtracts 2008, 21, 127-134.
- ^ Vince, R.; Daluge, S.; Brownell, J. J. Med. Chem. 1986, 29, 2400.
- ^ Daluge, S.; Vince, R. J. Org. Chem., 1978, 43, 2311-2320.
- ^ Vince, R.; Hua, M. J. Med. Chem. 1990, 33, 17.
- ^ Peterson, M. L.; Vince, R. J. Med. Chem. 1990, 33, 1214-1219.
- ^ (a) Toyota, A.; Habutani, C.; Katagiri, N.; Kaneko, C. Tetrahedron Lett. 1994, 35, 5665-5668. (b) Toyota, A.; Aizawa, M.; Habutani, C.; Katagiri, N.; Kaneko, C. Tetrahedron 1995, 36, 8783-8798.
- ^ Saito, Y.; Nakamura, M.; Ohno, T.; Chaicharoenpong, C.; Ichikawa, E.; Yamamura, S.; Kato, K.; Umezawa, K. J. Antibiotics 2000, 53, 309-313.
- ^ Kiss, L.; Forro, E.; Sillanpaa, R.; Fulop, F. Synthesis 2010, 153-160.
- ^ Rommel, M.; Ernst, A.; Koert, U. Eur. J. Org. Chem. 2007, 4408-4430.
- ^ Mineno, T.; Miller, M,. J. J. Org. Chem. 2003, 68, 6591-6596.