In North America, red blood cells (RBCs) are cryopreserved in a clinical setting using high glycerol concentrations (40% w/v) with slow cooling rates (~1°C/min) prior to storage at −80°C, while European protocols use reduced glycerol concentrations with rapid freezing rates. After thawing and prior to transfusion, glycerol must be removed to avoid intravascular hemolysis. This is a time consuming process requiring specialized equipment. Small molecule ice recrystallization inhibitors (IRIs) such as β-PMP-Glc and β-pBrPh-Glc have the ability to prevent ice recrystallization, a process that contributes to cellular injury and decreased cell viability after cryopreservation. Herein, we report that addition of 110 mM β-PMP-Glc or 30 mM β-pBrPh-Glc to a 15% glycerol solution increases post-thaw RBC integrity by 30-50% using slow cooling rates and emphasize the potential of small molecule IRIs for the preservation of cells.

Coffee consumption has been correlated with a decreased risk of developing Alzheimer’s disease (AD) and Parkinson’s disease (PD), but the mechanism by which coffee may provide neuroprotection in humans is not fully understood. We hypothesized that compounds found in brewed coffee may elicit neuroprotective effects by inhibiting the aggregation of amyloid-beta (Aβ) and tau (AD) or α-synuclein (PD). Three instant coffee extracts (light roast, dark roast, decaffeinated dark roast) and six coffee components [caffeine (1), chlorogenic acid (2), quinic acid (3), caffeic acid (4), quercetin (5), and phenylindane (6)] were investigated for their ability to inhibit the fibrillization of Aβ and tau proteins using thioflavin T (ThT) and thioflavin S (ThS) fluorescence assays, respectively. Inhibition of Aβ and α-synuclein oligomerization was assessed using ELISA assays. All instant coffee extracts inhibit fibrillization of Aβ and tau, and promote α-synuclein oligomerization at concentrations above 100 μg/mL. Dark roast coffee extracts are more potent inhibitors of Aβ oligomerization (IC50 ca. 10 μg/mL) than light roast coffee extract (IC50 = 40.3 μg/mL), and pure caffeine (1) has no effect on Aβ, tau or α-synuclein aggregation. Coffee components 2, 4, and 5 inhibit the fibrillization of Aβ at 100 μM concentration, yet only 5 inhibits Aβ oligomerization (IC50 = 10.3 μM). 1–5 have no effect on tau fibrillization. Coffee component 6, however, is a potent inhibitor of both Aβ and tau fibrillization, and also inhibits Aβ oligomerization (IC50 = 42.1 μM). Coffee components 4 and 5 promote the aggregation of α-synuclein at concentrations above 100 μM; no other coffee components affect α-synuclein oligomerization. While the neuroprotective effect of coffee consumption is likely due to a combination of factors, our data suggest that inhibition Aβ and tau aggregation by phenylindane 6 (formed during the roasting of coffee beans, higher quantities found in dark roast coffees) is a plausible mechanism by which coffee may provide neuroprotection. The identification of 6 as a dual-inhibitor of both Aβ and tau aggregation is noteworthy, and to our knowledge this is the first report of the aggregation inhibition activity of 6.

Low-molecular-weight ice recrystallization inhibitors (IRIs) are ideal cryoprotectants that control the growth of ice and mitigate cell damage during freezing. Herein, we describe a detailed study correlating the ice recrystallization inhibition activity and the cryopreservation ability with the structure of O-aryl-glycosides. Many effective IRIs are efficient cryoadditives for the freezing of red blood cells (RBCs). One effective cryoadditive did not inhibit ice recrystallization but instead inhibited ice nucleation, demonstrating the significance of inhibiting both processes and illustrating the importance of this emerging class of cryoprotectants.

Procedures for selective installation of acyl, silyl ether and para-methoxybenzyl (PMB) ether groups to glycoside substrates have been developed, employing phenylboronic esters as protected intermediates. The sequence of boronic ester formation, functionalization and deprotection can be accomplished with only a single purification step, and the boronic acid component can be recovered and reused after deprotection. Key advances include the identification of reaction conditions for installation of PMB groups in the presence of boronic esters, and the use of the 'phase switching' protocol developed by Hall and co-workers as an efficient method for boronic ester cleavage. The relatively mild conditions for boronate deprotection are tolerant of several functional groups, including esters, silyl ethers, ketals and thioglycosides.

Organoboron-mediated regioselective glycosylations were employed as key steps in the total synthesis of a branched pentasaccharide from a saponin natural product. The ability to use organoboron activation to differentiate OH groups in an unprotected glycosyl acceptor, followed by substrate-controlled reactions of the obtained disaccharide, enabled a streamlining of the synthesis relative to a protective group-based approach. This study revealed a matching/mismatching effect of the relative configuration of donor and acceptor on the efficiency of a regioselective glycosylation reaction, a problem that was solved through the development of a novel boronic acid-amine copromoter system for glycosyl acceptor activation.