Linker amine

The diisopropoxy-bis-(triethanolamine)-titanate, TYZORTE [36673-16-2] is an excellent cross-linker for aqueous solutions of hydroxyl-containing polymers. The reaction product of TYZORTPT with a mixture of trialkano1 amines and dialkanolarnines or monoalkano1 amines can be used to cure polyester-based powder coatings (109). Other ligands of this type iaclude triisopropano1 amine [122-20-3] ... 

The sensor ch consists of a glass de on to which a SO-nm thick gold film has been deposited. The gold film is then covered with a linker-layer to which a matrix of carboxylated dextran is attached. The dextran, which extends typically 100 nm out fi om the sur6ce, provides a hydrophilic, activatable and flexible polymer to which biomolecules can be coupled throu amine, sulphydryl, carboxyl and other groups. 

After finding the right combination for the diamine linkers, Yus et al. tried to determine whether it was compulsory to use two isoborneol-10-sulfonamide moieties. In this context, these authors have prepared the ligand depicted in Scheme 4.24 by reaction of the best amine linker, trani-cyclohexane-1,2-diamine, with camphorsulfonyl chloride and then with methanesulfonyl chloride, followed by reduction with AlH(i-Bu)2 and then hydrolysis.When this new ligand was involved in the enantioselective addition of ZnEt2 to acetophenone, the expected tertiary alcohol was obtained in excellent yield and enantioselectivity of 96% ee, as shown in Scheme 4.24. According to this result, the authors concluded that the second isoborneol unit seemed not to be necessary to obtain a high enantioselectivity. 

Silyl-based linker 23, cleaved by either basic (TBAF) or neutral (CsF) fluoridolysis to release carboxylic acids, alcohols, or amines, was prepared by treatment of a Grignard reagent to an aldehyde resin [28], To demonstrate the utility of this handle, /)-bromobenzoic acid was... 

Contrary to an alkoxy benzene scaffold, secondary amides were generated via novel aldehyde linker 43 based upon an indole scaffold (Scheme 15) [52]. The indole resin was prepared from indole-3-carboxy-aldehyde in two steps and reacted with amines under reductive conditions to generate resin-bound secondary amines. Treatment of the resin with... 

MAMP (Merrifield, Alpha-MethoxyPhenyl) resin 44 is an alternative to aldehyde linkers to construct TV-substituted amides [53], Nucleophilic displacement of the benzylic chloride with an amine followed by acylation yielded a secondary amide which was released upon a low ( 10%) concentration of TFA (Scheme 16). 

A variety of cleavage conditions have been reported for the release of amines from a solid support. Triazene linker 52 prepared from Merrifield resin in three steps was used for the solid-phase synthesis of aliphatic amines (Scheme 22) [61]. The triazenes were stable to basic conditions and the amino products were released in high yields upon treatment with mild acids. Alternatively, base labile linker 53 synthesized from a-bromo-p-toluic acid in two steps was used to anchor amino functions (Scheme 23) [62]. Cleavage was accomplished by oxidation of the thioether to the sulfone with m-chloroperbenzoic acid followed by 13-elimination with a 10% solution of NH4OH in 2,2,2-trifluoroethanol. A linker based on l-(4,4 -dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) primary amine protecting group was developed for attaching amino functions (Scheme 24) [65]. Linker 54 was stable to both acidic and basic conditions and the final products were cleaved from the resin by treatment with hydrazine or transamination with ra-propylamine. 

Traceless linker 60 based on a benzotriazole scaffold was reacted with amines and aldehydes to produce Mannich-type amine products [69]. Final product release was achieved by treatment with Grignard reagents (Scheme 29). 

Cleavage of all the linkers described above provide a functional group (carboxylic acid, amide, amine, etc) at the anchoring position. Silyl-based handles 71,72, and 73 as well as germanium-based handle 74 insert a C-H bond at the anchoring position and are referred to as traceless (Fig. 15) [82-... 

NOz O— y SOjNHCHjAr amine releasing linker (67) HOH PhSH ArCHjNHR... 

Brown EG, Nuss JM. Alkylation of Rink s amide linker on polystyrene resin a reductive amination approach to modified amine-linkers for the solid phase synthesis of /Y-substiuited amide derivatives. Tetrahedron Lett 1997 38 8457-8460. 

Brase S, Kobberling J, Enders D, Lazny R, Wang M, Brandtner S. Nitrogen-based linker. 3. Triazenes as robust and simple linkers for amines in solid-phase organic synthesis. Tetrahedron Lett 1999 40 2105-2108. 

Chhabra SR, Khan AN, Bycroft BW. Versatile Dde-based primary amine linkers for solid phase synthesis. Tetrahedron Lett 1998 39 3585-3588. 

Kay C, Murray PJ, Sandow L, Flolmes AB. A novel, chemically robust, amine-releasing linker. Tetrahedron Lett 1997 38 6941-6944. 

Succinic anhydride also is a convenient extender for creating spacer arms on chromatography supports. Supports derivatized with amine-terminal spacers may be succinylated to totally block the amine functionalities and form terminal carboxylic acid linkers for coupling amine-containing affinity ligands (Cuatrecasas, 1970). 

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