Building a Macrocyclic Toolbox from C‐Linked Carbohydrates Identifies Antiangiogenesis Agents from Zebrafish Assay

Abstract

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.

Evaluation of In-Batch and In-Flow Synthetic Strategies towards the Stereoselective Synthesis of a Fluorinated Analogue of Retro-Thiorphan

“…Then, N -Boc-protected amine 3 was de-protected with trifluoroacetic acid in dichlorometane (1:1). After a basic cleavage of the ammonium salt, product 4 was obtained in 95% yield [15]. Different attempts for enamine formation were performed on ethyl 4,4,4-trifluoroacetate, to form enamine 5 .…”

Stereoselective Synthesis of the C27–C35 Eribulin Fragment and Its Utilization in Building Structurally Diverse Macrocycles

“…[26][27][28][29][30][31][32] In the past few years, our group has reported the development of several methods for synthesizing diverse sets of macrocyclic compounds. 26,[34][35][36][37][38][39] The long-term goal of our current study is to assemble a macrocyclic chemical toolbox consisting of compounds originating from substructures of eribulin to permit the exploration of their biological properties in several challenging targets related to protein-protein interactions and deregulated signaling pathways.…”

Syntheses of Bis‐Triazole Linked Carbohydrate Based Macrocycles and Their Applications for Accelerating Copper Sulfate Mediated Click Reaction

“…The conformation-restricted nature of sugar ring allows the formation of chiral cavities, which are useful for guest encapsulation and chiral recognition. [32][33][34][35][36][37][38][39][40][41][42] A few examples of sugar based macrocycles containing the 1,2,3-triazole linkage are shown in Figure 1. [10,14] In recent years, copper (I) catalyzed azide alkyne cyclization reaction (CuAAC), or "click chemistry" strategy has shown great applications in many areas.…”