Rapid assembly of heterocycle grafted macrocycles via tandem one-pot double 1,3-dipolar cycloaddition reaction

Abstract

Synthesis of triazole linked macrocycles grafted with glycospiroheterocycle was accomplished by stereo- and regioselective tandem double 1,3-dipolar cycloaddition (1,3-DC) reaction. By this method we could construct complex chiral macrocycles in good yields from the easily available starting materials and we could achieve the synthesis of two heterocyclic rings involving simultaneous formation of five bonds in one-pot reaction. The structures of the macrocycles were confirmed by spectroscopic methods and single crystal XRD.

Growing Impact of Intramolecular Click Chemistry in Organic Synthesis

“…The developed protocol was also employed in similar synthesis of a series of macrocycles 416 using the Nbenzyl azidoisatin 415. [222] Likewise, another similar report demonstrated an one-pot intramolecular macrocyclization of azomethine ylides in order to produce a series of triazole-linked glycomacrocycles. [223] The metodology involves the one-pot three component reaction of O-propargyl nitro olefin 417, salicylaldehyde derived O-alkyl azides 418 or 419 and secondary amino acid 420 in the presence of CuI and DIPEA afforded the desired 1,4-triazole linked glycomacrocycles 421, and 422 in good yield (Scheme 90).…”

“…Synthesis of macrocycles 413 and 416 via tandem one-pot reaction. [222] Scheme 90. Synthesis of macrocycles 421 and 422 via tandem one-pot double 1,3-dipolar cycloaddition reaction.…”

“…Thus, the reaction of N ‐alkyl azidoisatin 412 , with glucose derived O ‐propargyl enone 410 , and secondary amino acid 411 using CuI, DIPEA afforded the 1,4‐triazole appended macrocycles 413 (Scheme 89). The developed protocol was also employed in similar synthesis of a series of macrocycles 416 using the N ‐benzyl azidoisatin 415 [222] …”

Multicomponent Click Reaction: An Indispensable Tool for Easy Access of Functionalized 1,2,3‐Triazoles

“…This approach resulted in the generation of 1,4-triazole-appended macrocycles 88 through the reaction of N-alkyl azidoisatin 87 with secondary amino acid 86 and glucose-derived O-propargyl enone 85, as depicted in Scheme 21b. [95] The methodology described was similarly employed in the comparable synthesis of macrocycles 91. This process involved utilizing O-propargyl enone 85, derived from glucose, along with amine 89, and Nbenzyl azidoisatin 90 as outlined in Scheme 21c.…”

“…This process involved utilizing O-propargyl enone 85, derived from glucose, along with amine 89, and Nbenzyl azidoisatin 90 as outlined in Scheme 21c. [95] A related study conducted by Rao et al demonstrated that azomethine ylides could be efficiently macrocyclic in a one-pot reaction, leading to the formation of various biocompatible triazole-linked glycomacrocycles. [96] This approach involves a one-pot three-component reaction, wherein O-propargyl nitro olefin 92, salicylaldehyde-derived O-alkyl azides 93 or 94, and secondary amino acid 95 reacted in the presence of CuI and DIPEA to yield the desired 1,4-triazole-linked glycomacrocycles 96 and 97 in good yield.…”