Solution-phase synthesis of a library of carbapeptide analogues based on glycosylamino acid scaffolds and their in silico screening and antimicrobial evaluation.
A well-organized and efficient approach toward the solution phase synthesis of a library of carbapeptide analogues based on glycosyl amino ester scaffold is described. The reported synthetic route involves a five step preparation of heptofuranuronamides 6a-h and octopyranuronamide 7e from glycosyl amino esters 1 and 7, respectively. Coupling of glycosyl amino esters 1 or 7 with three different N-Fmoc protected amino acids afford the N-Fmoc protected intermediates 2a-c and 7a. Deprotection of Fmoc group in 2a-c and 7a with piperidine gave respective compounds 3a-c and 7b with free amine. Subsequent coupling of 3a-c and 7b with different aromatic acids furnishes respective heptofuranuronates 4a-h and octopyranuronate 7c in good yields. The latter, on ester hydrolysis by LiOH gave the corresponding glycopeptide analogues 5a-h and 7d with terminal carboxyl group. The carboxyl group in these compounds was amidated with oxalyl chloride/ NH(4)OH to afford heptofuranuronamides 6a-h and octopyranuronamides 7e. In vitro screening of all compounds displayed moderate antifungal, antitubercular, and general antibacterial activities. Reverse docking calculations involving over 841 protein drug targets have identified two potential targets for these compounds. These results will form the basis for synthesizing second-generation antimicrobial compounds.
Pandey
Jyoti
J
Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow-226001, India.
Sharma
Anindra
A
Tiwari
Vinod K
VK
Dube
Divya
D
Ramachandran
Ravishankar
R
Chaturvedi
Vinita
V
Sinha
Sudhir K
SK
Mishra
Nripendra N
NN
Shukla
Praveen K
PK
Tripathi
Rama P
RP
D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques / Q000191:economics / Q000379:methods*; D005690:Galactose / Q000138:chemical synthesis / Q000737:chemistry; D005947:Glucose / Q000138:chemical synthesis / Q000737:chemistry; D006020:Glycopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D013329:Structure-Activity Relationship
D000596:Amino Acids; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D006020:Glycopeptides; D005947:Glucose; D005690:Galactose