A novel assembly of two structurally related 14-membered ring macrocyclic hepatitis C virus protease inhibitors is presented. Key to their successful construction was an ultimate ring-closing metathesis step on the respective highly functionalized dienyl-ureas. In the case of IDX316, this procedure significantly outperformed the original macrocyclizations in terms of reaction conditions, impurity profile, product isolation, and basic efficiency metrics. Simple nonchromatographic purification methods achieved sub-10-ppm ruthenium content in the isolated product. Overall yields to IDX316 from all five starting materials ranged from 11 to 40%, and the estimated process mass intensity was improved by a factor of 50 relative to the original unscalable discovery-based routes. Application of similar methodology in the case of IDX320 and first scale-up to halfkilogram batch sizes was demonstrated.

We present some necessary and sufficient conditions for a frame multiresolution analysis (FMRA) to admit a frame wavelet whose dyadic dilations and integer translates generate a frame for L 2 (R) and propose a construction of a wavelet, if it exists, which reduces to the classical orthonormal wavelet in the case of orthonormal multiresolution analysis. We also show that there always exists a frame for the detail space W 0 of a frame MRA consisting of the integer translates of two functions and give an explicit construction of them.

We first characterize the Riesz wavelets which are associated with multiresolution analyses (MRAs) and the Riesz wavelets whose duals are also Riesz wavelets. The characterizations show that if a Riesz wavelet is associated with an MRA, then it has a dual Riesz wavelet. We then improve Wang's characterization for a pair of biorthogonal wavelets to be associated with biorthogonal MRAs by showing that one of the two conditions in his characterization is redundant. 

No abstract

No abstract