Discovery and characterization of stereodefined PMO-gapmers targeting tau.

Antisense oligonucleotides (ASOs) are an important class of therapeutics to treat genetic diseases, and expansion of this modality to neurodegenerative disorders has been an active area of research. To realize chronic administration of ASO therapeutics to treat neurodegenerative diseases, new chemical modifications that improve activity and safety profiles are still needed. Furthermore, it is highly desirable to develop a single stereopure ASO with a defined activity and safety profile to avoid any efficacy and safety concerns due to the batch-to-batch variation in the composition of diastereomers.

α-Fluorination of tropane compounds and its impact on physicochemical and ADME properties.

Using an electrochemical C(sp)-H fluorination reaction, a series of α-fluorinated tropane compounds were synthesized and their druglikeness parameters were assessed to compare with the parent compounds. Improvements were observed in membrane permeability, P-gp liability, and inhibitory effects on hERG and Na1.5 channels, accompanied with a trend of decreased aqueous solubility and microsomal stability.

Differentiation of germination characteristics in Scutellaria rubropunctata (Lamiaceae) associated with adaptation to rheophytic habitats in the subtropical Ryukyu Islands of Japan.

Seed germination characteristics of a facultative rheophyte Scutellaria rubropunctata, a perennial skullcap endemic to the subtropical Ryukyu Islands of Japan, were investigated at temperatures of 15 °C, 20 °C, 25 °C, and 30 °C. The rheophytic type of S. rubropunctata showed relatively simultaneous germination times and reached high germination rates under all temperatures tested.

Unified synthesis of tirandamycins and streptolydigins.

The asymmetric total syntheses of tirandamycins A-D and tirandalydigin as well as the synthesis of the left-hand fragment of streptolydiginone and streptolydigin from a common intermediate are described. The comprehensive approach features the highly enantio- and diastereoselective assembly of the anti,anti,syn-stereotetrad unit which relies on a cinchona alkaloid-catalyzed asymmetric Morita-Baylis-Hillman reaction.

A new method for the protection of carboxylic acids with a triisopropylsiloxymethyl group.

An effective method for the protection of carboxylic acids with a triisopropylsiloxymethyl (TIPSOCH(2)) group is described. The reactions of various carboxylic acids with C(12)H(25)SCH(2)OTIPS in the presence of CuBr(2), Et(3)N, and molecular sieves 4A afford the corresponding triisopropylsiloxymethyl esters in good yields.