Darstellung der terminalen Pentadesoxydisaccharideinheit CB von Anthracyclin‐Antibiotica

Abstract

Durch sauer-katalysierte Addition des 2,3-Anhydro-ff-~-allopyranosids 2 an Diacetyl-L-rhamnal (1) wird unter Allylumlagerung das a,l -+ Cverkniipfte Disaccharid 3 gewonnen. Die Epoxidoffnung rnit Lithiumiodid fiihrt zu einem 1 : 4-Gemisch aus 4 rnit 3-iod-glum-und 7 rnit 2-iod-altroKonfiguration. Bei deren Reaktionen mit Natriumiodid erhdt man die entsprechenden Diiodide 5 bzw. 8. Letzteres gibt nach der Hydrierung das Pentadesoxydisaccharid 6 mit C-Iso-B-Struktur. In einer selektiven Hydrierung wird aus 7 das 6-Brom-2,6-didesoxy-Derivat 9 gewonnen, aus dem sich durch Umsetzung rnit Silberfluorid das exocyclische Glycal 12 darstellen lafit. Die nachfolgende Hydrierung erlaubt die Synthese des terminalen C -B-Pentadesoxydisaccharids 13 verschiedener Anthracyclin-Antibiotica. Preparation of the Terminal Pentadeoxy Disaccharide Unit C -B of Anthracycline AntibioticsDiacetyl-L-rhamnal (1) and 2,3-anhydro-a-~-allopyranoside 2 undergo an acid-catalyzed allylic rearrangement to yield the a , l -+ 4-linked disaccharide 3. Opening of the epoxide with lithium iodide results in a 1 : 4 mixture of 4 with 3-iodo-gluco and 7 with 2-iodo-altro configuration. Their reactions with sodium iodide give the corresponding diiodides 5 and 8, respectively. By hydrogenation of the latter the pentadeoxy disaccharide 6 with C-iso-B structure is obtained. The selective hydrogenation of 7 leads to the 6-bromo-2,6-dideoxy derivative 9 which is transformed into the exocyclic glycal 12 by reaction with silver fluoride. Subsequent hydrogenation allows the synthesis of the terminal C -B pentadeoxy disaccharide 13 of various anthracycline antibiotics.

Syntheses of deoxy oligosaccharides

“…Certain N-alkylation products [40] of daunosamine show a decreased ability for intercalation and eliminated the inhibitory action on cardiac guanylate cyclase as mentioned above [33]. The epimeric C-4' derivative (69), the sugar of which is called epi-daunosamine, extended the medical value to adriamycin-resistant carcinoma [41].…”

“…This is trans-opened by lithium iodide according to Ftirst-Plattner's rule. Upon different ways, two interesting products are obtained, either the original C-B disaccharide of aclacinomycin A 120 or its C-5 epimer 119 which contains one sugar in the D-configuration[69].Starting from methyl 2-deoxy-4,6-O-benzylidene-3-O-mesyl-~-D-arabino-hexopyranoside (121), a SN2 reaction by use of sodium azide in HMPT at 140 °C and NBScleavage gives compound 122. Following transglycosylation with benzyl alcohol and deprotection by Z6mplen transesterification to 123, acid-catalysed glycosylation with tri-O-acetyl-2-deoxy-L-fucose 124 affords the disaccharide 125.…”