Sharma Gangavaram V M, Subash Velaparthi, Reddy Nelli Yella, Narsimulu Kongari, Ravi Rapolu, Jadhav Vivekanand B, Murthy Upadhyayula S N, Kishore Kankipati Hara, Kunwar Ajit C
D-211, Discovery Laboratory, Organic Chemistry Division III, Hyderabad, 500 007, India.
Org Biomol Chem. 2008 Nov 21;6(22):4142-56. doi: 10.1039/b810817j. Epub 2008 Sep 18.
New C-linked carbo-beta-amino acids (beta-Caas), Cbz-(S)-beta-Caa-(NHBoc)-OMe (1) and Cbz-(R)-beta-Caa-(NHBoc)-OMe (2), with an additional amine group (methylamino group of NHBoc) at the C-1 position of the lyxofuranoside side chain and Boc-(S)-beta-Caa-(diFP)-OMe (3) and Boc-(R)-beta-Caa-(diFP)-OMe (4), with a C-difluorophenyl (diFP) moiety at the anomeric position of the lyxofuranoside side chain were prepared from D-mannose. Beta-peptides [tetra- and hexapeptides] were synthesized from these beta-Caas, 'epimeric' [at the amine stereocentre (C(beta))], using the concept of 'alternating chirality' to carry out their conformational studies [NMR (CDCl(3)), CD and MD]. In the monomer design, it was envisaged that the presence of an additional amine group in 1 or 2 would help in solubilizing the peptides in water, while, the C-difluorophenyl (diFP) moiety of 3 and 4 is expected to enhance the biological activity. The peptides having 1 and 2, though could not retain their 12-10-mixed helices in water, have shown moderate activity against gram positive and gram negative bacterial strains. The peptides prepared from 3 and 4, much against our expectations, did not display any biological activity.
新型C-连接的碳β-氨基酸（β-Caas），即Cbz-(S)-β-Caa-(NHBoc)-OMe（1）和Cbz-(R)-β-Caa-(NHBoc)-OMe（2），在呋喃木糖侧链的C-1位带有一个额外的胺基（NHBoc的甲基胺基），以及Boc-(S)-β-Caa-(diFP)-OMe（3）和Boc-(R)-β-Caa-(diFP)-OMe（4），在呋喃木糖侧链的异头位置带有一个C-二氟苯基（diFP）部分，是由D-甘露糖制备而成。利用“交替手性”的概念，从这些β-Caas（在胺立体中心（C(β)）处为“差向异构体”）合成了β-肽[四肽和六肽]，以进行它们的构象研究[核磁共振（CDCl₃）、圆二色光谱和分子动力学模拟]。在单体设计中，设想1或2中额外胺基的存在将有助于肽在水中的溶解，而3和4的C-二氟苯基（diFP）部分有望增强生物活性。含有1和2的肽虽然在水中不能保持其12 - 10混合螺旋结构，但对革兰氏阳性和革兰氏阴性细菌菌株显示出中等活性。由3和4制备的肽，与我们的预期相反，没有显示出任何生物活性。
