Chakraborty T K, Srinivasu P, Bikshapathy E, Nagaraj R, Vairamani M, Kumar S Kiran, Kunwar A C
Indian Institute of Chemical Technology and Centre for Cellular and Molecular Biology, Hyderabad-500 007, India.
J Org Chem. 2003 Aug 8;68(16):6257-63. doi: 10.1021/jo034586u.
Cyclic homooligomers of mannose-derived furanoid sugar amino acid 1 [H-Maa(Bn(2))-OH] were synthesized by using BOP reagent in the presence of DIPEA under dilute conditions that converted the sugar amino acid monomer directly into its cyclic homooligomers 3a and 4a. The glucose-based sugar amino acid 2 [H-Gaa(Bn(2))-OH] under the same reaction conditions gave a bicyclic lactam 5a as the major product. Cyclic homooligomers of 2 were prepared by cyclizing their linear precursors 6 and 7 leading to the formation of cyclic peptides 8a and 9a, respectively. Conformational analysis by NMR and constrained MD studies revealed that all the cyclic products, 3, 4, 8, and 9, had symmetrical structures. The deprotected cyclic trimer of Maa 3b displayed a conformation in which all the C=O and the N-H bonds of the molecule point in opposite directions. In the deprotected cyclic tetramer of Maa 4b, the COs and NHs were in the plane of the ring with the former pointing to outside and the latter inside the ring. The structure of the cyclic Gaa dimer 8b displayed an unusual six-membered intramolecular hydrogen bond between NH(i)() --> C3-O(i)()(-)(1) and a syn orientation between the C2-H and CO. In this molecule, the C2-hydrogens and the COs can be seen on one side of the ring while the NHs point to the other side. Addition of the bicyclic lactam 5b resulted in the influx of Na(+) ions across the lipid bilayer leading to the dissipation of valinomycin-mediated K(+) diffusion potential.
在二异丙基乙胺（DIPEA）存在下，使用BOP试剂在稀溶液条件下合成了甘露糖衍生的呋喃糖氨基酸1 [H-Maa(Bn(2))-OH]的环状同聚体，该条件可将糖氨基酸单体直接转化为其环状同聚体3a和4a。在相同反应条件下，基于葡萄糖的糖氨基酸2 [H-Gaa(Bn(2))-OH]生成了双环内酰胺5a作为主要产物。通过环化其线性前体6和7制备了2的环状同聚体，分别导致形成环状肽8a和9a。通过核磁共振（NMR）和受限分子动力学（MD）研究进行的构象分析表明，所有环状产物3、4、8和9均具有对称结构。Maa的脱保护环状三聚体3b呈现出一种构象，其中分子的所有C=O和N-H键指向相反方向。在Maa的脱保护环状四聚体4b中，羰基（COs）和氨基（NHs）位于环平面内，前者指向环外，后者指向环内。环状Gaa二聚体8b的结构在NH(i)() --> C3-O(i)()(-)(1)之间显示出异常的六元分子内氢键，并且C2-H和CO之间呈顺式取向。在该分子中，可以在环的一侧看到C2-氢原子和羰基，而氨基指向另一侧。双环内酰胺5b的加入导致Na(+)离子流入脂质双层，导致缬氨霉素介导的K(+)扩散电位消散。
