An efficient synthesis of a 4'-phosphonodifluoromethyl-3'-formyl-phenylalanine containing SRC SH2 ligand.
A CuBr-mediated, regioselective cross-coupling between methyl 2,5-diiodobenzoate (4) and [(diethoxyphosphinyl)difluoromethyl]zinc bromide is reported. Palladium-catalyzed incorporation of an amino acid side chain, followed by subsequent modifications resulted in the rapid construction of 2. Compound 2 was designed to engage Cys188 of the Src SH2 domain, however, this was not observed spectroscopically.
Facile synthesis of aryl(difluoromethyl)phosphonates through CuBr-mediated cross coupling reactions of [(diethoxyphosphinyl)difluoromethyl]zinc bromide with aryl iodides
Abstract The CuBr-promoted coupling reaction of [(diethoxyphosphinyl)difluoromethyl]zinc bromide 6 with aryl iodides in either DMF or DMA was examined to give a series of aryl(difluoromethyl)phosphonates. The coupling reaction was applicable to the selective synthesis of α,α-difluoro-4- iodobenzylphosphonale 11e, a useful intermediate for the preparation of F2Pmp. 1-[(Diethylphosphono)difluoromethyl] naphthalene 15 and the regioisomer 16 were obtained in high yields from 1- and 2-iodonaphthalene, respectively. The phosphonate 16 was transformed to the free acid 4a, a low molecular-mass inhibitor of protein phosphatases.
How to do a p-descent on an elliptic curve
In this paper, we describe an algorithm that reduces the computation of the (full) p-Selmer group of an elliptic curve E over a number field to standard number field computations such as determining the (p-torsion of) the S-class group and a basis of the S-units modulo pth powers for a suitable set S of primes. In particular, we give a result reducing this set S of 'bad primes' to a very small set, which in many cases only contains the primes above p. As of today, this provides a feasible algorithm for performing a full 3-descent on an elliptic curve over Q, but the range of our algorithm will certainly be enlarged by future improvements in computational algebraic number theory. When the Galois module structure of E[p] is favorable, simplifications are possible and p-descents for larger p are accessible even today. To demonstrate how the method works, several worked examples are included.