Method for the modification of alcohols on polymer supports

A method for the modification of alcohols on polymer supports comprising:

• (a) O-silylating an alcohol, RC—OH, with X2SiRARB, wherein X is a halogen, and RA and RB are each independently a C1-6 linear or C3-10 branched chain alkyl or an aryl group, in the presence of base under conditions to form a halosilyl compound;
• and
• (b) coupling said halosilyl compound with a polymeric alcohol support in the presence of base under conditions to form a polymer-linked composition having the following structure:
• wherein RA and RB are each independently a C1-6 linear or C3-10 branched chain alkyl or an aryl group;
• wherein is a polymeric support;
• wherein L is a linker selected from the group consisting of a single bond;
• a saturated or unsaturated oligomethylene chain, said oligomethylene chain being optionally interrupted by oxygen or sulfur atoms, an alkyl- or arylamino moiety, NH—CO or CO—NH;
• a 1,4-phenylene;
• or a 1,4-phenylenemethylene moiety, said moiety being optionally substituted by at least one linear or branched alkyl or alkoxy group and/or halogen atom;
• and
• wherein RC is a linear or branched acyclic, cyclic or multicyclic moiety, said moiety being optionally unsaturated and/or substituted by at least one hydrogen, ORi, amino, alkyl- or dialkylamino, NHCORi, halogen, CH2OH, CH2ORi, a substituted or unsubstituted linear or branched chain alkyl, (mono-, di- or tri)hydroxyalkyl, (mono-, di- or tri)acyloxyalkyl, arylalkyl or aryl group;
• wherein Ri is hydrogen, CHO, COORii, or a substituted or unsubstituted linear or branched chain alkyl, arylalkyl or aryl group aryl, alkylaryl or arylalkyl;
• wherein if RC is cyclic, said moiety is optionally aromatic and/or heterocyclic;
• or if multicyclic, said moiety is optionally a fused multicyclic, fully or partially aromatic and/or heterocyclic;
• and
• (c) subjecting said polymer-linked composition to one or more chemical reactions to generate a support-bound complex carbohydrate as the modified polymer-linked composition, which composition has the following structure:
• wherein RA and RB are each independently a C1-6 linear or C3-10 branched chain alkyl or an aryl group;
• wherein is a polymeric support;
• wherein L is a linker selected from the group consisting of a single bond;
• a saturated or unsaturated oligomethylene chain, said oligomethylene chain being optionally interrupted by oxygen or sulfur atoms, an alkyl- or arylamino moiety, NH—CO or CO—NH;
• a 1,4-phenylene;
• or a 1,4-phenylenemethylene moiety, said moiety being optionally substituted by at least one linear or branched alkyl or alkoxy group and/or halogen atom;
• and
• wherein RD is:
• wherein a, b, c, d, e, f, g, h, i, j, k, q, n, p, x and y are each independently 1, 2 or 3, with the proviso that RD is a carbohydrate having furanose of pyranose moieties whereby the sum of b and c is 1 or 2, the sum of d and f is 1 or 2, the sum of g and i is 1 or 2, and the sum of n, p, k and j is 2 or 3;
• wherein R0, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and R13 are each independently hydrogen, OH, ORi, NH2, NHCORi, F, CH2OH, CH2ORi, a protecting group, a substituted or unsubstituted linear or branched chain alkyl, (mono-, di- or tri)hydroxyalkyl, (mono-, di- or tri)acyloxyalkyl, arylalkyl or aryl group;
• wherein Ri is hydrogen, CHO, COORii, a substituted or unsubstituted linear or branched chain alkyl, arylalkyl or aryl group or a saccharide moiety having the structure:
• wherein Y and Z are each independently NH or O;
• wherein r, s, t, u, v, w, z and z′ are each independently 0, 1 or 2, with the proviso that z and z′ bracketed structures represent furanose or pyranose moieties and the sum of s and t is 1 or 2, and the sum of u and w is 1 or 2, and with the proviso that z and z′ are not simultaneously 0;
• wherein Rx is hydrogen, a linear or branched chain alkyl, acyl, arylalkyl or aryl group;
• wherein R14, R15, R17, R18, R19, and R20 are each independently hydrogen, OH, ORiii, NH2, NHCORiii, F, CH2OH, CH2ORiii, or a substituted or unsubstituted linear or branched chain alkyl, (mono-, di- or tri)hydroxyalkyl, (mono-, di- or tri)acyloxyalkyl, arylalkyl or aryl group;
• wherein R16 is hydrogen, COOH, COORii, CONHRii, a substituted or unsubstituted linear or branched chain alkyl or aryl group;
• wherein Riii is hydrogen, CHO, COORiv, or a substituted or unsubstituted linear or branched chain alkyl, arylalkyl or aryl group;
• and wherein Rii and Riv are each independently H, or a substituted or unsubstituted linear or branched chain alkyl, arylalkyl or aryl group, or wherein any two of R0-R13, taken together, comprise a cyclic protecting group;
• wherein the dotted line represents an optional double bond;
• wherein when said double bond is present, R0 and R3 are not both OH or amino;
• and
• wherein said carbohydrate is optionally linked to an amino acyl or hydroxy acyl residue of a substructure by substitution of a side group or terminal group substituent thereof selected from the group consisting of OH, COOH and NH2, said substructure being:
• A—Bm—Cn—Dp—Eq—F
• wherein m, n, p and q are 0, 1, 2 or 3 such that m+n+p+q≦6;
• wherein A, B, C, D, E and F are independently amino acyl or hydroxy acyl residues wherein A is N- or O-terminal and is either a free amine or an ammonium form when A is amino acyl or a free hydroxy when A is hydroxy acyl, or A is alkylated, arylated or acylated;
• and wherein F is either a free carboxylic acid, primary carboxamide, mono- or dialkyl carboxamide, mono- or diaryl-carboxamide, linear or branched chain (carboxy)alkyl carboxamide, linear or branched chain (alkoxycarbonyl)alkyl-carboxamide, linear or branched chain (carboxy)arylalkylcarboxamide, linear or branched chain (alkoxycarbonyl)-alkylcarboxamide, an oligoester fragment comprising from 2 to about 20 hydroxy acyl residues, a peptidic fragment comprising from 2 to about 20 amino acyl residues, or a linear or branched chain alkyl or aryl carboxylic ester;
• and
• (d) treating said modified polymer-linked composition with a cleaving agent under suitable conditions to generate an alcohol, RD—OH, and a reusable polymeric alcohol support.