Site-Specific Dolasynthen Antibody-Drug Conjugates Exhibit Consistent Pharmacokinetic Profiles across a Wide Range of Drug-to-Antibody Ratios.

Key defining attributes of an antibody-drug conjugate (ADC) include the choice of the targeting antibody, linker, payload, and the drug-to-antibody ratio (DAR). Historically, most ADC platforms have used the same DAR for all targets, regardless of target characteristics. However, recent studies and modeling suggest that the optimal DAR can depend on target expression level and intratumoral heterogeneity, target internalization and trafficking, and characteristics of the linker and payload.

De Novo Asymmetric Synthesis of Phoracantholide J.

A de novo asymmetric total synthesis of the macrolide natural product (S)-phoracantholide J has been achieved in 10 steps from the commodity chemicals (1-pentyne, ethyl acrylate, acetaldehyde, and hydrogen). The asymmetry of the route was introduced by a Noyori reduction of a 3-yn-2-one, which makes the route equally amenable to the synthesis of either enantiomer. In addition, this route relies upon an alkyne zipper, a hydroalkynylation, and a macrolactonization to complete the synthesis.