Efficient Syntheses of Thiadiazole Peptides

Abstract

Novel N-(Cbz-aminoacyl)thiosemicarbazides 3a-c were cyclized by treatment with sulfuric acid to give 1,3,4-thiadiazoles 4a-c. Compounds 4a-c reacted with N-(Cbz-aminoacyl)- and -dipeptidoylbenzotriazoles to afford chirally pure 1,3,4-thiadiazol-2-yl-substituted amino acids 6a-c and dipeptides 7a-c.

Straightforward Synthesis of Various Chiral Pyrimidines Bearing Stereogenic Center at the C2 position, Including C-Terminal Peptide Isosters

“…This is also particularly desirable as N-heterocycles are considered as highly valuable C-terminal peptides isosteres but their access is still challenging. [9][10][11][12][13][14][15][16][17][18][19][20][21] We present herein our results in this field.…”

“…Scope and limitation for the use of various -chiral carboxamides.As previously stated, peptides with N-heterocyles C-terminal ends are highly desirable compounds. Indeed, C-terminal modified peptidomimetics have been used to limit the enzymatic degradation and to enhance the bioavaibility [9][10][11][12][13][14][15][16][17][18][19][20][21]. To this endeavour, pyrimidines 3ab' and 3ae' derived from Phenylalanine and Valine were deprotected in acidic conditions and then coupled to Cbz-Ala-OH in the presence of PyBOP to give the corresponding C-terminal modified pseudo-peptides 19 and 20 in 65 and 55% yields respectively (Scheme 5).…”

A Facile Synthesis of 1,5‐Disubstituted Tetrazole Peptidomimetics by Desulfurization/Electrocyclization of Thiopeptides

“…Peptide bond isosteres have shown enhanced metabolic stability and physicochemical properties and, thus, various isosteres such as triazole, tetrazole, oxadiazole, thiadiazole, urea,and others have been successfully explored to improve the pharmacokinetic properties of native peptides. The cis ‐amide configuration plays a significant role in the molecular recognition and biological activity of peptides as shown by the role of proline (Pro) and other N ‐alkylamino acids found in a variety of peptides, such as cyclosporine and didemnin .…”

One Pot Synthesis of Novel 4-[(5-Aryl-1,3,4-thiadiazol-2-ylamino)methyl]phenol Derivatives

“…1,3,4-噻二唑衍生物因其特殊结构而具有良好的杀 虫 [1] 、杀菌 [2,3] 、除草 [4] 、植物生长调节 [5] 、药物活性 [6,7] 等多种功效而倍受关注, 同时由于其环上的 N, S 原子均 能参与生命活动, 因而也具有广泛的生理活性, 如抗 炎 [8] 、 抗菌 [9] 、 抗癌 [10,11] 等作用, 已成为当今的研究热点.…”