TY - JOUR
T1 - A Route to Artificial Glycoconjugates and Oligosaccharides via Enzymatically Resolved Glycals
T2 - Dramatic Effects of the Handedness of the Sugar Domain Upon the Properties of an Anthracycline Drug
AU - Berkowitz, David B.
AU - Danishefsky, Samuel J.
AU - Schulte, Gayle K.
PY - 1992/6/1
Y1 - 1992/6/1
N2 - Racemic, fully synthetic glycals of considerable structural variety may be kinetically resolved via enzymatically mediated transesterification using Lipase PS-30 from Pseudomonas cepacia as catalyst and vinyl acetate as acyl donor. This methodology provides convenient access to a pool of optically enriched d- and l-glycals. These glycals may be employed as building blocks, both as glycosyl donors and glycosyl acceptors, to generate artificial oligosaccharides. Thus the d-glucal analogue 7, bearing a phenyl group at C-5, was converted to the corresponding 1,2-anhydrosugar(s) 8/9, which could be coupled directly to a second glycal. Alternatively, the 1,2-anhydrosugar could be converted to the corresponding β-glycosyl fluoride 14 or β-glycosyl sulfoxides 18a,b. Both 14 and 18a,b were glycosylated, with a glycal or a terminating sugar, in good yield. Conversely, the l-glucal analogue 3 was employed as a glycosyl acceptor, with l-fucosyl fluoride(s) (α:β = 1:1) as the glycosyl donor, to furnish the artificial “L,L”-disaccharide 17. Enzymatically resolved l- and d-glycals were also used to construct novel glycoconjugates of daunomycinone with di-sym-collidinyliodonium perchlorate as the coupling reagent. By employing each antipode of the 5-phenyl analogue of galactal, (+)- and (-)-25, as glycosyl donor, a pair of diastereomeric 5′-phenyl analogues of daunomycin 22 and 23, was obtained. These two compounds differ only in the handedness (l or d) of their carbohydrate sectors, yet exhibit markedly different biological properties. Interestingly, X-ray crystal structure determinations for 22 and 23 reveal fundamentally different overall molecular shapes for the two compounds.
AB - Racemic, fully synthetic glycals of considerable structural variety may be kinetically resolved via enzymatically mediated transesterification using Lipase PS-30 from Pseudomonas cepacia as catalyst and vinyl acetate as acyl donor. This methodology provides convenient access to a pool of optically enriched d- and l-glycals. These glycals may be employed as building blocks, both as glycosyl donors and glycosyl acceptors, to generate artificial oligosaccharides. Thus the d-glucal analogue 7, bearing a phenyl group at C-5, was converted to the corresponding 1,2-anhydrosugar(s) 8/9, which could be coupled directly to a second glycal. Alternatively, the 1,2-anhydrosugar could be converted to the corresponding β-glycosyl fluoride 14 or β-glycosyl sulfoxides 18a,b. Both 14 and 18a,b were glycosylated, with a glycal or a terminating sugar, in good yield. Conversely, the l-glucal analogue 3 was employed as a glycosyl acceptor, with l-fucosyl fluoride(s) (α:β = 1:1) as the glycosyl donor, to furnish the artificial “L,L”-disaccharide 17. Enzymatically resolved l- and d-glycals were also used to construct novel glycoconjugates of daunomycinone with di-sym-collidinyliodonium perchlorate as the coupling reagent. By employing each antipode of the 5-phenyl analogue of galactal, (+)- and (-)-25, as glycosyl donor, a pair of diastereomeric 5′-phenyl analogues of daunomycin 22 and 23, was obtained. These two compounds differ only in the handedness (l or d) of their carbohydrate sectors, yet exhibit markedly different biological properties. Interestingly, X-ray crystal structure determinations for 22 and 23 reveal fundamentally different overall molecular shapes for the two compounds.
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U2 - 10.1021/ja00038a011
DO - 10.1021/ja00038a011
M3 - Article
AN - SCOPUS:0026651052
SN - 0002-7863
VL - 114
SP - 4518
EP - 4529
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 12
ER -