Regioselective reductive cleavage of bis-benzylidene acetal: stereoselective synthesis of anticancer agent OGT2378 and glycosidase inhibitor 1,4-dideoxy-1,4-imino-l-xylitol.
A highly regioselective reductive cleavage of the bis-benzylidene acetal of D-mannitol was performed using a BF(3) x Et(2)O/Et(3)SiH reagent system. A chiral intermediate 6 thus obtained was efficiently utilized in the stereoselective synthesis of the anticancer agent OGT2378 (3) and glycosidase inhibitor derivative N-tosyl 1,4-dideoxy-1,4-imino-L-xylitol (22). Chemoselective reduction of azido epoxide 10 followed by regioselective intramolecular cyclization of amino epoxide 11 resulted in the exclusive formation of deoxyidonojirimycin derivative 12. By changing the order of deprotection, the chiral intermediate 6 was readily transformed to glycosidase inhibitor derivative 22.
Aravind
Appu
A
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036, India.
Sankar
Muthukumar Gomathi
MG
Varghese
Babu
B
Baskaran
Sundarababu
S
D000080:Acetals / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001597:Benzylidene Compounds / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050113:Imino Furanoses / Q000138:chemical synthesis / Q000737:chemistry; D050111:Imino Sugars / Q000138:chemical synthesis* / Q000737:chemistry; D008353:Mannitol / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D014993:Xylitol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
C467078:1,4-dideoxy-1,4-imino-xylitol; D000080:Acetals; D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D004791:Enzyme Inhibitors; D050113:Imino Furanoses; D050111:Imino Sugars; D010880:Piperidines; D008353:Mannitol; D006026:Glycoside Hydrolases; C476104:sinbaglustat; D014993:Xylitol