RESUMEN
A novel method for Fmoc/tBu solution-phase peptide synthesis and the development of a new benzyl-type GAP protecting group is reported. This new GAP protecting group is utilized in place of a polymer support, facilitating CâN Fmoc peptide synthesis without chromatography, recrystallization, or polymer supports. The GAP group can be added and removed in high yield, and was used to synthesize over 1 gram of the immunostimulant, thymopentin, in high overall yield (83%) and purity (99%).
RESUMEN
The development of environmentally benign, operationally simple, and economically viable synthetic methodologies has been a great challenge in organic synthesis. Group-assisted purification (GAP) chemistry was established to enable the synthesis of organic compounds without using traditional purification technologies, such as column chromatography and recrystallization. This concept/technology should encourage the synthetic community to make more efforts on searching for environmentally benign reagents and reactions to reduce the waste generated from silica and solvents, particularly toxic solvents; also, to reduce production/synthesis expenses, manpower, and energy. This review will discuss the GAP concept/technology and related reactions that were mainly conducted in the PI's laboratories after 2010.
Asunto(s)
Iminas/aislamiento & purificación , Compuestos Organofosforados/aislamiento & purificación , Iminas/química , Estructura Molecular , Compuestos Organofosforados/químicaRESUMEN
Carbamoyl anions were found to smoothly react with chiral N-phosphonyl imines in toluene at -78 °C to r.t. using LiHMDS as the base. Group-assisted purification (GAP) has been utilized to give the pure amides without using column chromatography or recrystallization. The asymmetric reaction resulted in chiral N-phosphonyl amino amides with good to excellent yields (71-99%) and good crude diastereoselectivities (dr 84:16-95:5). In this GAP procedure, the crude solids are washed with diethyl ether to afford the pure products, as revealed by (1)H NMR analysis; GAP washing consistently increases the diastereopurity of the products, resulting in excellent diastereoselectivities, often with final dr > 99:1. Interestingly, the diastereoenriched products can be obtained either in the ether solution or as the suspended solid, depending on the substrate.