First Glycosylation of Decarestrictine B and D: A Route to Hybrid Antibiotics

Abstract

The naturally occurring ten-membered lactones decarestrictine B (4) and D (5), which lower cholesterol levels, were glycosylated with deoxygenated 2-selenoglycosyl acetates 7 a, 7 b, and glycal 10 (obtained from d-glucose), and glycal 13 (obtained from l-rhamnose). Depending on the glycosylation method employed, the triol decarestrictine D was glycosylated with a high degree of regioselectivity. A set of hybrid structures were yielded by O-deblocking and in most cases reductive removal of a halogen or a phenylselenyl group from C-2 of the glycosides 14 a ± f, 20 a, 20 b, and 24. These hybrids were subjected to preliminary biological tests in which the novel glycoconjugates 15 d and 15 e displayed DNA-binding properties.Abstract in German: Die natürlich vorkommenden, den Cholesterinspiegel senkenden zehngliedrigen Lactone Decarestrictin B (4) und D (5) wurden mit den aus d-Glucose bzw. l-Rhamnose erhältlichen desoxygenierten 2-Seleno-glycosylacetaten 7 a,b sowie mit den Glycalen 10 und 13 glycosidisch verknüpft. In Abhängigkeit von der gewählten Glycosylierungsmethode konnte das Triol Decarestrictin D mit hoher Positionsselektivität glycosyliert werden. Nach Abspaltung der Schutzgruppen und in vielen Fällen reduktiver Entfernung von Halogen oder der Phenylselenyl-Gruppe an C-2 der Glycoside 14 a ± f, 20 a,b und 24 wurden verschiedene Hybridstrukturen erhalten, die ersten biologischen Tests unterzogen wurden. Für die Bisglycoside 15 d und 15 e wurde DNA-Affinität gefunden. Scheme 1. Preparation of glycosyl donors 6, 7, 9, and 10.

Total Synthesis of the Postulated Structure of Fulicineroside

“…In the NMR spectroscopic analysis of the glycosylated natural product an emphasis was set on the postulated uncommon β‐linked L ‐rhodinose (Figure 5). Signals for the rhodinosyl‐H‐1′′′ of the β‐linked products 1 ( δ =4.45 ppm) and 88 ( δ =4.53 ppm) were consistent with data of Kirschning50 for a synthetic β‐linked rhodinose ( δ =4.45 ppm) but differed from Řezanka’s value ( δ =4.78 ppm). The latter value matched better with the data for the α‐rhodinose compound 89 ( δ =4.89 ppm) and Kirschning’s data ( δ =4.93 ppm for an α‐rhodinose).…”

Natural Product Hybrids as New Leads for Drug Discovery

“…As the number of pathogens that are resistant towards existing antibiotics increases, the construction of new therapeutic agents by hybridization is regarded as an important approach in this field. The glycosylation of decarestrictine D ( 273 ), a naturally occurring 10‐membered lactone with an iodo derivative of L ‐rhodinose ( 274 ), one of the rare sugars commonly found as constituents of angucycline antibiotics, led to the formation of the anomeric glycosides 275 a and 275 b 99. In preliminary tests, these hybrids displayed DNA‐binding properties.…”

The stereochemistry of the Nozaki-Hiyama-Kishi reaction and the construction of 10-membered lactones. The enantioselective total synthesis of (-)-decarestrictine D

“…While the relative stereochemistry was provided by Xray analysis 1b , its absolute configuration has been recently established by total synthesis 3 and X-ray analysis of a chiral derivative 2 . Other members of the 10-membered lactone family 4 include decarestrictines A (2) and B (3), phoracantholide I (4) 5 and pyrenolide A (5) 6 .…”