Stereoselective synthesis of (1-alkoxyalkyl) alpha- and beta-D-glucopyranosiduronates (acetal-glucopyranosiduronates): a new approach to specific cytostatics for the treatment of cancer.
The reaction of methyl 2,3,4,6-tetra-O-acetyl-1-O-trimethylsilyl-beta- and -alpha-D-glucopyranuronate severally with the dimethyl or diethyl acetals of formaldehyde, bromoacetaldehyde, propionaldehyde, 3-benzyloxypropionaldehyde, 5-carboxypentanal, and 2-bromohexanal in the presence of catalytic amounts of trimethylsilyl trifluoromethanesulfonate at -78 degrees gave the corresponding (1-alkoxyalkyl) alpha- and beta-glycosides (acetal-glucopyranosiduronates) with retention of configuration at C-1 in yields of 41-91%. Instead of the dialkyl acetals, the corresponding aldehydes and alkyl trimethylsilyl ether can be used. Deacetylation gave the corresponding methyl (acetal-beta- and -alpha-D-glucopyranosid)uronates in good yield. De-esterification of methyl [(1R)-1-methoxybutyl beta-D-glucopyranosid]uronate with esterase gave the acetal-beta-D-glucopyranosiduronic acid which was an excellent substrate for beta-D-glucuronidase.
Tietze
L F
LF
Institut für Organische Chemie der Georg-August-Universität, Göttingen, F.R.G.
Seele
R
R
Leiting
B
B
Krach
T
T
D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D005965:Glucuronates / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D005965:Glucuronates; D011355:Prodrugs