Substituted 2-azabicyclo[2.1.1]hexanes as constrained proline analogues: implications for collagen stability.

Tytuł:: Substituted 2-azabicyclo[2.1.1]hexanes as constrained proline analogues: implications for collagen stability.
Autorzy:: Jenkins CL; Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Lin G
Duo J
Rapolu D
Guzei IA
Raines RT
Krow GR
Źródło:: The Journal of organic chemistry [J Org Chem] 2004 Dec 10; Vol. 69 (25), pp. 8565-73.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.
Język:: English
Imprint Name(s):: Publication: Columbus Oh : American Chemical Society
Original Publication: Easton, Pa. [etc.]
MeSH Terms:: Bridged Bicyclo Compounds, Heterocyclic/*chemical synthesis
Collagen/*chemistry
Hexanes/*chemical synthesis
Proline/*analogs & derivatives
Proline/*chemical synthesis
Bridged Bicyclo Compounds, Heterocyclic/chemistry ; Hexanes/chemistry ; Models, Molecular ; Molecular Structure ; Proline/chemistry ; Protein Conformation
Grant Information:: AR 44276 United States AR NIAMS NIH HHS; GM 08506 United States GM NIGMS NIH HHS; S10 RR 04981-01 United States RR NCRR NIH HHS; S10 RR 08389-01 United States RR NCRR NIH HHS
Substance Nomenclature:: 0 (Bridged Bicyclo Compounds, Heterocyclic)
0 (Hexanes)
9007-34-5 (Collagen)
9DLQ4CIU6V (Proline)
Entry Date(s):: Date Created: 20041204 Date Completed: 20050214 Latest Revision: 20161124
Update Code:: 20240104
DOI:: 10.1021/jo049242y
PMID:: 15575731
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Among the proteinogenic amino acids, only proline is a secondary amine and only proline has a saturated ring. Electronegative substituents on C-4 (that is, C(gamma)) have a substantial effect on the trans/cis ratio of the prolyl peptide bond and the pucker of the pyrrolidine ring. 2-Azabicyclo[2.1.1]hexane is, in essence, a proline analogue with two C(gamma) atoms, one in each of the two prevalent ring puckers of proline. Here, 2-azabicyclo[2.1.1]hexane analogues of 2S-proline, (2S,4S)-4-hydroxyproline, and (2S,4S)-4-fluoroproline residues were synthesized, and their trans/cis ratios were shown to be invariant in a particular solvent. Thus, the substitution of a proline residue on C-4 affects the trans/cis ratio by altering the pucker of its pyrrolidine ring. This finding has implications for the conformation of collagen, which has an abundance of 2S-proline and (2S,4R)-4-hydroxyproline residues, and can be stabilized by (2S,4R)-4-fluoroproline and (2S,4S)-4-fluoroproline residues.

Erratum in: J Org Chem. 2006 Feb 17;71(4):1754.

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