Alicyclic β- and γ-Amino Acids: Useful Scaffolds for the Stereocontrolled Access to Amino Acid-Based Carbocyclic Nucleoside Analogs

Abstract

Stereocontrolled synthesis of some amino acid-based carbocyclic nucleoside analogs containing ring C=C bond has been performed on β- and γ-lactam basis. Key steps were N-arylation of readily available β- or γ-lactam-derived amino ester isomers and amino alcohols with 5-amino-4,6-dichloropyrimidine; ring closure of the formed adduct with HC(OMe)3 and nucleophilic displacement of chlorine with various N-nucleophiles in the resulting 6-chloropurine moiety.

Antiproliferative Activity of (−)‐Isopulegol‐based 1,3‐Oxazine, 1,3‐Thiazine and 2,4‐Diaminopyrimidine Derivatives

“…Addition of 2,4‐dichloro‐5‐fluoropyrimidine 18 a to these building blocks in the presence of Et 3 N in EtOH provided 5‐fluoro analogues 19 a – i . [103] These were then applied in microwave‐assisted S N Ar coupling reactions with 4‐aminobenzotrifluoride in EtOH at 150 °C to produce 20 a – i as solid precipitates in good yields (Scheme 5 ). [104] …”

“…Addition of 2,4-dichloro-5-fluoropyrimidine 18 a to these building blocks in the presence of Et 3 N in EtOH provided 5-fluoro analogues 19 a-i. [103] These were then applied in microwave-assisted S N Ar coupling reactions with 4-aminobenzotrifluoride in EtOH at 150 °C to produce 20 a-i as solid precipitates in good yields (Scheme 5). [104] Due to the anticancer potential of pyrimidines substituted at various positions as well as fused with other heterocyclic rings, [105] coupling reactions were performed by utilising 2,4,5trichloropyrimidine 18 b and 5-amino-4,6-dichloropyrimidine 18 c as reagents.…”

“…Consequently, we decided to convert primary aminodiols 2 a , b , 6 , 10 , 12 and aminotriol 4 as well as aminoalcohols 8 a , b and 14 into their pyrimidine scaffolds. Addition of 2,4‐dichloro‐5‐fluoropyrimidine 18 a to these building blocks in the presence of Et 3 N in EtOH provided 5‐fluoro analogues 19 a – i [103] . These were then applied in microwave‐assisted S N Ar coupling reactions with 4‐aminobenzotrifluoride in EtOH at 150 °C to produce 20 a – i as solid precipitates in good yields (Scheme 5).…”

Divergent Synthesis, Antiproliferative and Antimicrobial Studies of 1,3‐Aminoalcohol and 3‐Amino‐1,2‐Diol Based Diaminopyrimidines

“…Key intermediates 10a -d, obtained by addition of aminoalcohols 5 -7 and aminodiol 8 to 2,4-dichloro-5fluoropyrimidine (9) in the presence of Et 3 N in EtOH (aminoalcohols 5 -7 was transformed to 10a -d after 24 h without the presence of by products, indicated by TLC), [62] could be easily isolated by simple column chromatography to afford high (10a and 10d) or moderate yields (10b and 10c) (Scheme 1). In the next step, after a microwave-assisted S N Ar coupling reaction of 10a -c with 4-aminobenzotrifluoride (11) in EtOH at 150 °C, the crude products were filtered then recrystallized in CH 2 Cl 2 to provide N 2 -aryl substituted pyrimidine derivatives 12a -c as solid precipitates in good yields (over 76 %), [63] whereas the coupling reaction at the remaining chlorine at position 2 in adduct 10d was unsuccessful either under standard heating or microwave-assisted conditions.…”