Enantioselective synthesis of iclaprim enantiomers--a versatile approach to 2-substituted chiral chromenes.
Both enantiomers of the DHFR inhibitor iclaprim (R)-1 and (S)-1 were synthesized from the cyclopropyl homoallyl alcohols (R)-6 and (S)-6, respectively. As key steps these transformations include a Mitsunobu reaction and the formation of the diaminopyrimidine unit prior to a novel cyclization procedure to obtain the desired chromene heterocycle. The moderate enantioselectivity of the products (R)-1 and (S)-1 is related to the Mitsunobu reaction, which unfortunately did not proceed with complete inversion of configuration.
Tahtaoui
Chouaib
C
ARPIDA AG, Duggingerstrasse 23, 4153 Reinach, Switzerland. chouaib@hotmail.com
Demailly
Arnold
A
Guidemann
Carole
C
Joyeux
Cécile
C
Schneider
Peter
P
D000438:Alcohols / Q000737:chemistry; D001578:Benzopyrans / Q000138:chemical synthesis*; D005493:Folic Acid Antagonists / Q000138:chemical synthesis; D011743:Pyrimidines / Q000138:chemical synthesis; D013237:Stereoisomerism; D013762:Tetrahydrofolate Dehydrogenase
D000438:Alcohols; D001578:Benzopyrans; D005493:Folic Acid Antagonists; D011743:Pyrimidines; C486448:iclaprim; D013762:Tetrahydrofolate Dehydrogenase