Biomaterial Database

Design and synthesis of a 3,4-dehydroproline amide discovery library. 2007

Stefan Werner, and Dhanalakshmi Kasi, and Kay M Brummond

Center for Chemical Methodologies and Library Development (UPCMLD), University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. stw15@pitt.edu

The synthesis of a discovery library of 80 3,4-dehydroproline amides was achieved in a four-step reaction sequence from easily accessible 3-aminoallene-3-carboxylate methyl esters. Diversification of these proline mimics was introduced at five different sites: the substituents at the 3-pyrroline unit (R1, R2, R3), at the nitrogen (R4), and the C-terminus (R5). The 3-pyrroline scaffold was synthesized in excellent yields by a silver-catalyzed intramolecular cyclization of aminoallenes, followed by N-functionalization reactions. Maximum diversity was introduced in the final step of the reaction sequence by taking advantage of the carboxylic acid handle of the 3-pyrroline subunit. Amide coupling reactions using polystyrene-carbodiimide (PS-carbodiimide) and 1-hydroxybenzotriazole (HOBt) under microwave irradiation led to 3,4-dehydroproline amides that were obtained in purities greater than 85% by LC/MS/ESLD after scavenging the excess HOBt on a silica-bound carbonate SPE cartridge.

UI	MeSH Term	Description	Entries
D011392	Proline	A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.	L-Proline,L Proline
D002627	Chemistry, Physical	The study of CHEMICAL PHENOMENA and processes in terms of the underlying PHYSICAL PHENOMENA and processes.	Physical Chemistry,Chemistries, Physical,Physical Chemistries
D000577	Amides	Organic compounds containing the -CO-NH2 radical. Amides are derived from acids by replacement of -OH by -NH2 or from ammonia by the replacement of H by an acyl group. (From Grant & Hackh's Chemical Dictionary, 5th ed)	Amide
D015394	Molecular Structure	The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.	Structure, Molecular,Molecular Structures,Structures, Molecular
D016208	Databases, Factual	Extensive collections, reputedly complete, of facts and data garnered from material of a specialized subject area and made available for analysis and application. The collection can be automated by various contemporary methods for retrieval. The concept should be differentiated from DATABASES, BIBLIOGRAPHIC which is restricted to collections of bibliographic references.	Databanks, Factual,Data Banks, Factual,Data Bases, Factual,Data Bank, Factual,Data Base, Factual,Databank, Factual,Database, Factual,Factual Data Bank,Factual Data Banks,Factual Data Base,Factual Data Bases,Factual Databank,Factual Databanks,Factual Database,Factual Databases
D055598	Chemical Phenomena	The composition, structure, conformation, and properties of atoms and molecules, and their reaction and interaction processes.	Chemical Concepts,Chemical Processes,Physical Chemistry Concepts,Physical Chemistry Processes,Physicochemical Concepts,Physicochemical Phenomena,Physicochemical Processes,Chemical Phenomenon,Chemical Process,Physical Chemistry Phenomena,Physical Chemistry Process,Physicochemical Phenomenon,Physicochemical Process,Chemical Concept,Chemistry Process, Physical,Chemistry Processes, Physical,Concept, Chemical,Concept, Physical Chemistry,Concept, Physicochemical,Concepts, Chemical,Concepts, Physical Chemistry,Concepts, Physicochemical,Phenomena, Chemical,Phenomena, Physical Chemistry,Phenomena, Physicochemical,Phenomenon, Chemical,Phenomenon, Physicochemical,Physical Chemistry Concept,Physicochemical Concept,Process, Chemical,Process, Physical Chemistry,Process, Physicochemical,Processes, Chemical,Processes, Physical Chemistry,Processes, Physicochemical