High-Throughput Assessment of Structural Continuity in Biologics.

We demonstrate a high-throughput chemoprinting platform that confirms the consistency in the higher-order structure of protein biologics and is sensitive enough to detect single-point mutations. This method addresses the quality and consistency of the tertiary and quaternary structure of biologic drug products, which is arguably the most important, yet rarely examined, parameter. The method described uses specific small-molecule ligands as molecular probes to assess protein structure.

An application of borane as a protecting group for pyridine.

Efforts to couple 4 with 12 employing base mediation are problematic due to the formation of 6. To circumvent this issue, 12 was converted to the pyridine borane complex (13). Alkylation of 4 with 13 provided 3 after removal of the borane under acidic conditions and saponification of the ester.

Efficient transamidation of primary carboxamides by in situ activation with N,N-dialkylformamide dimethyl acetals.

Two protocols for the transamidation of primary amides with primary and secondary amines, forming secondary and tertiary amides, respectively, are described. Both processes employ N,N-dialkylformamide dimethyl acetals for primary amide activation, producing N'-acyl-N,N-dialkylformamidines as intermediates, as widely documented in the literature. Although the latter intermediates react irreversibly with amines by amidinyl transfer, we show that in the presence of certain Lewis acid additives efficient acyl transfer occurs, providing new and useful methods for amide exchange.

A synthesis of the diazonamide heteroaromatic biaryl macrocycle/hemiaminal core.

[reaction: see text] Stille coupling of an arylstannane aminal 19 with the palladium complex 23 leads to atropisomeric esters 28 and 29. Conversion to macrocycle 30 is demonstrated, a potential precursor of natural and unnatural diazonamides.