Solid phase synthesis of β-peptoids:: N-substituted β-aminopropionic acid oligomers

被引:117
作者
Hamper, BC [1 ]
Kolodziej, SA [1 ]
Scates, AM [1 ]
Smith, RG [1 ]
Cortez, E [1 ]
机构
[1] Monsanto Co, St Louis, MO 63167 USA
关键词
D O I
10.1021/jo971675w
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
A solid-phase organic synthesis method has been developed for the preparation of N-substituted-beta-aminopropionic acid oligomers or beta-peptoids 1. Treatment of polymer-bound 4-(benzyloxy)benzyl acrylate 2 with primary amines afforded N-substituted beta-alanines 3. Polymer loadings and product conversions were determined by direct cleavage of resin-bound materials and measurement by H-1 NMR with an internal standard. The NMR method was used to establish loading of all resin-bound intermediates including acrylic acid. Acylation with acryloyl chloride followed by Michael addition of primary amines to the acrylamide allowed preparation of di-beta-peptoids. By a linear set of seven reactions, trimeric N-benzyl-beta-aminopropionic acid was prepared in 67% overall yield. Single-bead FT-IR microspectroscopy was used to acquire spectra of the resin bound mono-beta-peptoids, di-beta-peptoids, and acrylamide intermediates. A combinatorial library of defined mixtures of tri-beta-peptoids was prepared by mixing equimolar amounts of the mono-beta-peptoid resins and carrying them through two sequences of the acylation-Michael addition. The identity of a sample mixture was determined by LC-MS analysis of the cleavage product.
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页码:708 / 718
页数:11
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