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Building a Macrocyclic Toolbox from C ‐Linked Carbohydrates Identifies Antiangiogenesis Agents from Zebrafish Assay
Author(s) -
Jogula Srinivas,
Dasari Bhanudas,
Khatravath Mahender,
Chandrasekar Gayathri,
Kitambi Satish Srinivas,
Arya Prabhat
Publication year - 2013
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201300548
Subject(s) - chemistry , moiety , stereochemistry , ring (chemistry) , diastereomer , tripeptide , amino acid , biochemistry , organic chemistry
We report the synthesis of four different types of macrocyclic‐derived glycohybrids from carbohydrates that have an amino acid moiety in the large‐ring skeleton. These macrocyclic glycohybrids were obtained from α‐ C ‐1H‐ and β‐ C ‐1H‐linked carbohydrates. In one series, we utilized ring‐closing metathesis as the “stitching technology” to obtain two different macrocycles, i.e., trans equatorial–axial C‐1H and C‐5H and cis axial–axial C‐1H and C‐5H. The click approach was the key reaction in our second series to obtain two other macrocyclic compounds, i.e., trans equatorial–axial C‐1H and C‐5H and cis axial–axial C‐1H and C‐5H. The evaluation of this toolbox resulted in the identification of two unique compounds as antiangiogenesis agents in an embryonic zebrafish assay. Interestingly, in both cases, the macrocyclic compounds that have a cis relationship (i.e., axial–axial orientation) between C‐1H and C‐5H showed activity and their other diastereomers (i.e., equatorial–axial C‐1H and C‐5 H) with a trans relationship did not show any effect.