Efficiencies of reductive amination reactions on different solid supports
TETRAHEDRON
LETTERS
Tetrahedron Letters 39 (1998) 9279-9282
Pergamon
Efficiencies of Reductive Amination Reactions on Different Solid Supports
Chinh T Bui, Firas A. Rasoul, Francesca Ercole, Yen Pham and N Joe Maeji*
Cluron TechnologiesPry Ltd.. 11 Duerdin Street. Cla.~aon,Vic. 3168, Australia
Received 12 August 1998; accepted 1 October 1998
Abstract:
Rreductive amination on resins derivatized with 5-(4-forntyl-3,5-dimethoxyphenoxv)valeric acid linker (Barallv linker, 1) 1 has been reported to be less" effective than on resin derivatized with its" ntonomethoxy analog (2): due to steric hindrance of the extra methoxv fimctional group within the molecule. 3 A study of these linkers indicate that the origins of such data is also related to the spacer and solid support used in the study. Depending on the linker, spacer and solid phase, .yields from 10% to 75% were obtained under exactly the same reaction conditions. © 1998 ElsevierScienceLtd. All rights reserved.
The choice of solid support and linker are important factors for success in solid phase synthesis. ~ Unlike solution phase synthesis, where an optimisation study will result in reproducible reactions, time consuming validation steps usually required in solid phase synthesis may only be specific for a particular solid support s
Here, we present a comparative study of reaction rates, yields, and purity to assess the effect of the solid phase and a six bond spacer arm in a model reductive amination.
We compared aminomethylated and chloromethylated Synphase crowns 6 used with the Multipin method of solid phase synthesis, 7 with aminomethylated (1.0 mmol/g, 500-595 lam, Polymer Laboratories) and chloromethylated (0.99 mmol/g, 400500 Jam, Polymer Laboratories) resin beads. For comparative purposes, we chose resins with relatively large bead sizes as they can be considered individual "reactors" that allow syntheses of many different compounds in common reaction flasks but still allow
LETTERS
Tetrahedron Letters 39 (1998) 9279-9282
Pergamon
Efficiencies of Reductive Amination Reactions on Different Solid Supports
Chinh T Bui, Firas A. Rasoul, Francesca Ercole, Yen Pham and N Joe Maeji*
Cluron TechnologiesPry Ltd.. 11 Duerdin Street. Cla.~aon,Vic. 3168, Australia
Received 12 August 1998; accepted 1 October 1998
Abstract:
Rreductive amination on resins derivatized with 5-(4-forntyl-3,5-dimethoxyphenoxv)valeric acid linker (Barallv linker, 1) 1 has been reported to be less" effective than on resin derivatized with its" ntonomethoxy analog (2): due to steric hindrance of the extra methoxv fimctional group within the molecule. 3 A study of these linkers indicate that the origins of such data is also related to the spacer and solid support used in the study. Depending on the linker, spacer and solid phase, .yields from 10% to 75% were obtained under exactly the same reaction conditions. © 1998 ElsevierScienceLtd. All rights reserved.
The choice of solid support and linker are important factors for success in solid phase synthesis. ~ Unlike solution phase synthesis, where an optimisation study will result in reproducible reactions, time consuming validation steps usually required in solid phase synthesis may only be specific for a particular solid support s
Here, we present a comparative study of reaction rates, yields, and purity to assess the effect of the solid phase and a six bond spacer arm in a model reductive amination.
We compared aminomethylated and chloromethylated Synphase crowns 6 used with the Multipin method of solid phase synthesis, 7 with aminomethylated (1.0 mmol/g, 500-595 lam, Polymer Laboratories) and chloromethylated (0.99 mmol/g, 400500 Jam, Polymer Laboratories) resin beads. For comparative purposes, we chose resins with relatively large bead sizes as they can be considered individual "reactors" that allow syntheses of many different compounds in common reaction flasks but still allow
References: Org. Chem. 1990, 55, 3730., Songster, MF.; Vagner J.; Barany, G., Lett. Pept. Sci., 1995, 2, 265. 2. Fivush, M. A.; Willson, T. M. TetrahedronLett, 1997, 38, 7151. 3. Sarantakis, D.; Bicksler, J.J. Tetrahedron Lett, 1997, 38, 7325. 4. Li, W.;Yan, B. J. Org. Chem., 1998, 63, 4092. 5. Burgess, K.; Lim, D. Chem. Commun., 1997, 785. 6. Wendeborn, S.; Beaudegnies, R.; Ang, K H.; Maeji, N J., Biotechnol. Bioeng. (Comb. Chem)., 1998, 61, 89. 7. Geysen, H.M.; Meloen, RH.; Bavteling, SJ. Proc. Natl. Aead. Sci. U.S.A. 1984, 81, 3998. Maeji, N.J.; Bray, A.M; Valerio R 9 Thompson, L.A; Ellman, JA. ( 'hem. Rev., 1996, 96, 555.