A flexible approach to azasugars: asymmetric total syntheses of (+)-castanospermine, (+)-7-deoxy-6-epi-castanospermine, and (+)-1-epi-castanospermine.
The asymmetric total synthesis of natural azasugars (+)-castanospermine, (+)-7-deoxy-6-epi-castanospermine, and synthetic (+)-1-epi-castanospermine has been accomplished in nine to ten steps from a common chiral building block (S)-8. The method features a powerful chiral relay strategy consisting of a highly diastereoselective vinylogous Mukaiyama-type reaction with either chiral or achiral aldehydes (> or = 95% de; de=diastereomeric excess) and a diastereodivergent reduction of tetramic acids, which allows formation of three continuous stereogenic centers with high diastereoselectivities. The method also provides a flexible access to structural arrays of 5-(alpha-hydroxyalkyl)tetramic acids, such as 17/34, and 5-(alpha-hydroxyalkyl)-4-hydroxyl-2-pyrrolidinones, such as 18 and 25/35 a. The method constitutes the first realization of the challenging chiral synthons A and D and thus of the conceptually attractive retrosynthetic analysis shown in Scheme 1 in a highly enantioselective manner.
Liu
Gang
G
Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P. R. China.
Wu
Tian-Jun
TJ
Ruan
Yuan-Ping
YP
Huang
Pei-Qiang
PQ
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D007212:Indolizines / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D013237:Stereoisomerism; D054836:Indolizidines
D000470:Alkaloids; D001372:Aza Compounds; D007212:Indolizines; C065752:7-deoxycastanospermine; C037806:castanospermine; D054836:Indolizidines