Premium
Synthesis of 5‐Azacastanospermine, a Conformationally Restricted Azafagomine Analogue
Author(s) -
Søndergaard Kåre,
Liang Xifu,
Bols Mikael
Publication year - 2001
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20010601)7:11<2324::aid-chem23240>3.0.co;2-y
Subject(s) - epimer , reductive amination , castanospermine , stereochemistry , chemistry , stereocenter , hydrogenolysis , aldehyde , stereoselectivity , adduct , amination , enzyme , enantioselective synthesis , organic chemistry , catalysis
The 5‐aza‐6‐deoxy analogue of castanospermine (±)‐ 5 a and its 1‐epimer (±)‐ 5 b was synthesized. The synthesis started from the known compound 5‐benzyloxy‐7‐hydroxyhepta‐1,3‐diene, which was protected and subjected to Diels–Alder reaction with 4‐phenyl‐1,2,4‐triazoline‐3,5‐dione to give two epimeric adducts. One of these was transformed through epoxidation, acetolysis, a series of side‐chain transformations that converted it into a terminally protected aldehyde, deprotection, and hydrogenolysis/reductive amination into 5 a . By a similar set of reactions the other adduct epimer was converted into 5 b . The castanospermine analogue 5 a was a weaker inhibitor of almond β ‐glucosidase and rice α ‐glucosidase than castanospermine ( 2 ) or 1‐azafagomine ( 4 ), but was considerably more potent than its epimer 5 b . This suggests that these enzymes have a strong preference for binding substrates or azasugars with the 6‐OH in an axial conformation.