One pot oxidative dehydration - oxidation of polyhydroxyhexanal oxime to polyhydroxy oxohexanenitrile: A versatile methodology for the facile access of azasugar alkaloids.
A unique oxidative dehydration-oxidation of polyhydroxy-oxime (7) to the corresponding ketonitrile (8) in one pot is reported for the first time in carbohydrate literature. Key ketonitrile intermediate (8) upon palladium hydroxide mediated cascade reaction afforded 1-deoxynojirimycin (DNJ) 1b in moderate diastereoselectivity. The cascade reaction involves the conversion of nitrile to amine, heteroannulation, reduction of the imine and subsequent debenzylation to furnish the azasugars. This oxidative dehydration-oxidation and reductive heteroannulation methodology is successfully utilized for the total synthesis of 1-deoxynojirimycin (1b), miglitol (2) and miglustat (3).
Technology Development Center, Custom Pharmaceutical Services, Dr. Reddy's Laboratories Ltd., Miyapur, Hyderabad 500049, India; Department of Organic Chemistry, Andhra University, Visakhapatanum 530003, India.
Sandip R
SR
Khobare
Technology Development Center, Custom Pharmaceutical Services, Dr. Reddy's Laboratories Ltd., Miyapur, Hyderabad 500049, India.
Vikas
V
Gajare
Technology Development Center, Custom Pharmaceutical Services, Dr. Reddy's Laboratories Ltd., Miyapur, Hyderabad 500049, India.
E Vishnuvardhan
EV
Reddy
Technology Development Center, Custom Pharmaceutical Services, Dr. Reddy's Laboratories Ltd., Miyapur, Hyderabad 500049, India.
Rajender
R
Datrika
Technology Development Center, Custom Pharmaceutical Services, Dr. Reddy's Laboratories Ltd., Miyapur, Hyderabad 500049, India.
Malavika
M
Banda
Department of Organic Chemistry, Andhra University, Visakhapatanum 530003, India.
Vidavalur
V
Siddaiah
Integrated Product Development, Innovation Plaza, Dr. Reddy's Laboratories Ltd., Bachupalli, Qutubullapur, R. R. Dist., 500072, Andhra Pradesh, India.
Sharad S
SS
Pachore
Technology Development Center, Custom Pharmaceutical Services, Dr. Reddy's Laboratories Ltd., Miyapur, Hyderabad 500049, India.
Upadhya
U
Timanna
Integrated Product Development, Innovation Plaza, Dr. Reddy's Laboratories Ltd., Bachupalli, Qutubullapur, R. R. Dist., 500072, Andhra Pradesh, India.
Vilas H
VH
Dahanukar
Integrated Product Development, Innovation Plaza, Dr. Reddy's Laboratories Ltd., Bachupalli, Qutubullapur, R. R. Dist., 500072, Andhra Pradesh, India. Electronic address: syam_kmr@yahoo.com.
U K
UK
Syam Kumar
D003890:Desiccation; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D010091:Oximes / Q000737:chemistry*
D009570:Nitriles; D010091:Oximes
Alcohol oxidation & oxime dehydration; Cascade reaction; Deoxynojirimycin; Miglitol; Miglustat; Reductive aminative cyclization