DIPROLINE [[beta]]-TURN MIMICS: SUBSTITUTION EFFECTS ON ALLOWED CONFORMATIONS. William H. Ojalaa, Paul W. Bauresb, Rodney L. Johnsonb, William B. Gleasonb, aUniversity of St. Thomas, St. Paul, MN 55105, USA, bUniversity of Minnesota, Minneapolis, MN 55455, USA
Diproline segments have the potential to serve as [[beta]]-turn mimics with substitution at the [[alpha]]- and [[beta]]- positions providing a means of mimicking the side-chains of turn residues. Although the [[beta]]-turn conformations of unsubstituted diprolyl segments have previously been explored, the effect of prolyl ring substituents upon the conformational preferences of diprolyl templates has not been studied. To address this issue the diproline peptides tosyl-trans-3-Me-D-Pro-D-Pro-NH2 (I), tosyl-cis-3-Me-D-Pro-D-Pro-NH2 (II), and Boc-L-Pro-trans-3-Me-L-Pro-D-Pro-NH2 (III) have been synthesized and their crystal structures determined. In addition, the crystal structure of Boc-L-Tic-D-Pro-NH2 (IV), where a Tic (1,2,3,4-tetrahydro-3-isoquinolinyl) residue is substituted for a prolyl residue, has also been studied. The results show that in homochiral diprolines a 3-methyl group in a cis relationship with the carbonyl group induces a conformation which is different from that favored in the corresponding unsubstituted diproline.
Crystal Data: (I): C18H25O4N3S, P21, a=7.652(3), b=13.400(5), c=9.725(3) Å, [[beta]]=108.06(3)o, R=0.074; (II): C18H25O4N3S, P21, a=8.781(2), b=6.107(2), c=17.374(1) Å, [[beta]]=91.38(1)o, R=0.040; (III): C21H34O5N4 . 1/2H2O, P21, a=14.675(3), b=10.106(5), c=15.994(5) Å, [[beta]]=99.64(2)o, R=0.050; (IV): C20H27O4N3, P212121, a=10.598(3), b=29.245(2), c=6.517(2) Å, R=0.036.