A facile and efficient synthetic approach to novel lariat macrocyclic diamides and bis macrocyclic diamides

Abstract

The hydroxy macrocycles 8, 19a-c were prepared in 40-55% yields by reacting the dipotassium salts 2a-c with each of epichlorohydrin (7) and bis(chloromethyl) derivative 18. Acylation of the hydroxyl group of each of 8, 19a-c with 2-chloroacetylchloride (9) in DMF gave the corresponding esters 10, 20a,b. Reaction of the latter with different amines as well as phenoxides furnished exclusively the target lariat macrocycles 13a-c, 22a-c and 23a-c in 60-63% and 50-55% yields, respectively. Amination of two equivalents of the chloroacetyloxy derivative 10 and 2a,b with 1 equiv. of piperazine (12c) afforded the corresponding bismacrocycles 14 and 26a,b respectively, in 60-65% yields. Moreover, the novel bis(macrocycles) 27-29 were prepared in 45-50% yields, respectively, by reacting each of 20a,b with the dipotassium salts 2b, 24 and 25 respectively, in DMF. Introduction.

Synthesis and Anti‐influenza Virus Activity of Novel bis(4H‐chromene‐3‐carbonitrile) Derivatives

“…As a part of an ongoing research program on Michael addition reactions and bis‐heterocyclic compounds with a suitable spacer , and encouraged by the potency of the clinically useful chromene derivatives in treatment of cancer and inflammation and other activities, we report the results of our investigations concerning the synthesis of novel bis‐4 H ‐chromene‐3‐carbonitrile derivatives aiming at exploring of their anti‐influenza virus activities.…”

Synthesis of mixed‐donor azaoxathia macrocyclic tetraamides, acyclic polyether di/and tetraamides and their C‐pivot lariat derivatives

“…Thus, continuing our course for the preparation of macrocycles with amide functional groups [43][44][45][46][47], lariat macrocycles and bis-macrocycles [48][49][50][51], we describe herein a simple and efficient route for the synthesis of mixed N, O, and S-donor 27-30 membered macrocyclic tetraamides, polyacyclic di-and tetraamides as well as their lariat derivatives with strong donor heteroatoms in the side arm in good yields. In this way, we hope to achieve a higher level of cation binding than generally observed with simple monocyclic crown compounds.…”

Synthesis of C‐pivot lariat ethers

“…Abbas et al . [123–126] used an approach similar to that described by Katritzky [122] for the synthesis of azacrown ethers with pendant alkylaminoacetyloxy or phenoxy groups 898 , 899 , 900 , 901 , 902 , 903 , 904 , 905 , 906 , 907 , 908 , 909 , 910 , 911 , 912 , 913 , 914 , 915 , 916 , 917 (Tables 53–56) from the corresponding hydroxyl azacrown ethers 884 , 886 , 887 , 888 , 890 , 891 , 892 , 893 , and 897 by initial acylation of the hydroxyl group in these compounds with 2‐choloroacetyl chloride followed by reaction with the appropriate alkyl amine or phenol.…”

“…The hydroxyazacrown ethers 884 , 886 , 887 , 888 , and 890 , 891 , 892 , 893 , 894 were obtained by reaction of the appropriate dipotassium salts 883 with epichlorohydrin ( 7 ) for 884 , 1,3‐bis(2‐chloromethylphenoxy)propan‐2‐ol ( 885 ) for 886 , 887 , 888 , 1,3‐bis(2‐chloroacetyloxy‐aminophenoxy)propan‐2‐ol ( 889a ) and 1,3‐bis(2‐chloroacetyloxy‐aminothiophenoxy)propan‐2‐ol ( 889b ) for 890 , 891 , 892 , 893 , 894 , respectively [124, 125] (Scheme ).…”