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With all stereoisomers of pyrans 1 and 2 and ¦Ã-amino acids 3 in hand, we began to investigate methods for the union of these chiral fragments en route to macrocycles ABC-5 and ACB-5. Although the efficiency of solid-phase synthesis for the preparation of large compound libraries has been well documented (33, 34), polymer-assisted parallel solution-phase synthesis offers several advantages (35, 36). Benefits include rapid analogue generation, reduced optimization time, and ease of reaction monitoring.We thus settled on a parallel solution-phase synthesis strategy utilizing silica-supported reagents and scavengers. |
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