Terminally-branched polymeric linkers and polymeric conjugates containing the same

A method of preparing a polymeric transport system, comprising a) reacting a compound of Formula (IXa) ##STR32## with a compound of Formula (X) ##STR33## wherein:

• Y.sub.1-2 are independently O or S;
• M is selected from either X or Q;
• wherein X is an electron withdrawing group and Q is a moiety containing a free electron pair positioned three to six atoms from C(.dbd.Y.sub.2);
• R.sub.2-5 are independently selected from the group consisting of hydrogen, C.sub.1-6 alkyls, C.sub.3-12 branched alkyls, C.sub.3-8 cycloalkyls, C.sub.1-6 substituted alkyls, C.sub.3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C.sub.1-6 heteroalkyls and substituted C.sub.1-6 heteroalkyls;
• (m) is zero or one;
• (n) is a positive integer;
• (p) is zero or a positive integer;
• Z is an electron withdrawing group;
• B.sub.2 is a leaving group;
• R.sub.1 is a polymeric residue;
• and
• b) reacting the resultant compound with a sufficient amount of a biologically active moiety having an OH group.

A method of preparing a polymeric transport system, comprising

• a) reacting a compound of Formula (IX) ##STR34## wherein:
• B.sub.3 is a cleavable protecting group;
• Y.sub.1 is O or S;
• R.sub.4-5 are independently selected from the group consisting of hydrogen, C.sub.1-6 alkyls, C.sub.3-12 branched alkyls, C.sub.3-8 cycloalkyls, C.sub.1-6 substituted alkyls, C.sub.3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C.sub.1-6 heteroalkyls and substituted C.sub.1-6 heteroalkyls;
• (m) is zero or one;
• (n) is a positive integer;
• (p) is zero or a positive integer;
• and
• Z is an electron withdrawing group with a biologically active moiety having an OH group
• b) deprotecting the resultant intermediate by removing B.sub.3 ;
• and
• c) reacting the deprotected intermediate compound with a compound of Formula (X) ##STR35## wherein:
• B.sub.2 is a leaving group;
• Y.sub.2 is O or S;
• M is selected from either X or Q;
• wherein X is an electron withdrawing group and Q is a moiety containing a free electron pair positioned three to six atoms from C(.dbd.Y.sub.2);
• R.sub.2-3 are independently selected from the group consisting of hydrogen, C.sub.1-6 alkyls, C.sub.3-12 branched alkyls, C.sub.3-8 cycloalkyls, C.sub.1-6 substituted alkyls, C.sub.3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C.sub.1-6 heteroalkyls and substituted C.sub.1-6 heteroalkyls;
• and
• R.sub.1 is a polymeric residue.