Method of Producing Hydroxyalkyl Starch Derivatives

Abstract

The present invention relates to methods of producing hydroxyalkyl starch (HAS) derivatives having a structure according to formula (I) comprising reacting HAS of formula (I) at its optionally oxidized reducing end or a HAS derivative, obtainable by reacting HAS of formula (I) at its optionally oxidized reducing end with a compound (D) comprising at least one functional group Z 1 capable of being reacted with the optionally oxidized reducing end of the HAS and at least one functional group W, with a compound (L) comprising at least one functional group Z 1 capable of being reacted with said HAS, or at least one functional group Z 2 capable of being reacted with functional group W comprised in said HAS derivative, and at least one functional group X capable of being reacted with a functional group Y of a further compound. The present invention further relates to HAS derivatives and pharmaceutical compositions comprising them.

1 - 59 . (canceled) 
     
     
         60 . A hydroxyalkyl starch (HAS) derivative obtainable by a method comprising reacting
 (a) a first HAS derivative obtained by reacting HAS of formula (I)   
       
         
           
           
               
               
           
         
         at its optionally oxidized reducing end with a compound (D), said compound (D) comprising at least one functional group Z 1  capable of being reacted with the optionally oxidized reducing end of the HAS, and at least one functional group W, 
         said reacting being carried out via the reaction of the functional group Z 1  comprised in the compound (D) with the optionally oxidized reducing end of the HAS wherein the functional group Z 1  is selected from the group consisting of 
       
       
         
           
           
               
               
           
         
         wherein G is O or S and, if present twice, independently O or S, 
         with 
         (b) a compound (L) comprising at least one functional group Z 2  capable of being reacted with the at least one functional group W of said first HAS derivative, and at least one functional group X capable of being reacted with a functional group Y of a further compound (M), 
         said reaction of said first HAS derivative with the compound (L) being carried out via the reaction of the functional group Z 2  comprised in the compound (L) with the functional group W comprised in the compound (D) to give a second HAS derivative, 
         (i) wherein the functional group W or the functional group Z 2  is —SH and the functional group Z 2  or the functional group W is selected from the group consisting of 
       
       
         
           
           
               
               
           
         
       
       wherein Hal is Cl, Br, or I,
 (ii) or wherein the functional group W or the functional group Z 2  is selected from the group consisting of an activated ester or a carboxy group which is optionally transformed into an activated ester and the functional group Z 2  or the functional group W is selected from the group consisting of 
 
       
         
           
           
               
               
           
         
         wherein G is O or S and, if present twice, independently O or S, and R′ is methyl, 
         (c) said method further comprising reacting said second HAS derivative with the further compound (M) via the reaction of the functional group X comprised in the compound (L) with the functional group Y comprised in the further compound (M), 
         wherein said functional group Y is a thio group, and the functional group X is selected from the group consisting of 
       
       
         
           
           
               
               
           
         
       
       wherein Hal is Cl, Br or I. 
     
     
         61 . A pharmaceutical composition comprising, in a therapeutically effective amount, a HAS derivative according to  claim 60 .