Paulsen, Hans;
Matzke, Michael;
Orthen, Bruno;
Nuck, Rolf;
Reutter, Werner
Monosaccharide mit Stickstoff im Ring, XXXIX. Synthese von modifizierten α‐L‐Fucosidase‐Inhibitoren, die 1,5‐Didesoxy‐1,5‐imino‐L‐fucit als Basisstruktur enthalten
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Titel:
Monosaccharide mit Stickstoff im Ring, XXXIX. Synthese von modifizierten α‐L‐Fucosidase‐Inhibitoren, die 1,5‐Didesoxy‐1,5‐imino‐L‐fucit als Basisstruktur enthalten
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<jats:p><jats:bold>Monosaccharides Containing Nitrogen in the Ring, XXXIX. — Synthesis of Analogues of 1,5‐Dideoxy‐1,5‐imino‐<jats:sc>L</jats:sc>‐fucitol, Inhibitors of α‐<jats:sc>L</jats:sc>‐Fucosidase</jats:bold></jats:p><jats:p>Variation of the side chain in the 1,3‐dithiane derivative <jats:bold>1</jats:bold> of <jats:sc>D</jats:sc>‐galactose leads to a series of analogues of 1,5‐dideoxy‐1,5‐imino‐<jats:sc>L</jats:sc>‐fucitol (deoxyfuconojirimycin) (<jats:bold>33</jats:bold>), which are potent inhibitors of α‐<jats:sc>L</jats:sc>‐fucosidase. Cleavage of the dithioacetal in <jats:bold>5</jats:bold> followed by reduction of the aldehyde <jats:bold>6</jats:bold> and deblocking results in 1,5‐dideoxy‐1,5‐imino‐<jats:sc>L</jats:sc>‐galactitol (<jats:bold>8</jats:bold>). The aldehyde <jats:bold>6</jats:bold> is converted by Wittig reaction to <jats:bold>10</jats:bold> and <jats:bold>14</jats:bold> via <jats:bold>9</jats:bold> and <jats:bold>13</jats:bold>, which are homologues of 1,5‐dideoxy‐1,5‐imino‐<jats:sc>L</jats:sc>‐fucitol (<jats:bold>33</jats:bold>). Cyclization of the Wittig product <jats:bold>15</jats:bold> yields the γ‐lactam <jats:bold>18</jats:bold>. After reduction of the acetylated γ‐lactam <jats:bold>19</jats:bold> and subsequent deblocking the trihydroxyindolizidine <jats:bold>24</jats:bold> is obtained, which is an analogue of castanospermine with <jats:sc>L</jats:sc>‐<jats:italic>fuco</jats:italic> configuration. The chloride <jats:bold>30</jats:bold>, which is available from <jats:bold>27</jats:bold>, can be converted by intramolecular substitution and removal of the blocking groups to the bicyclic aziridine derivative (3<jats:italic>R</jats:italic>,4<jats:italic>S</jats:italic>,5<jats:italic>R</jats:italic>,6<jats:italic>S</jats:italic>) ‐1‐azabicyclo[4.1.0]heptane‐3,4,5‐triol (<jats:bold>32</jats:bold>). First results on the inhibitory activities of all new analogues on α‐<jats:sc>L</jats:sc>‐fucosidase are presented.</jats:p>