Several N-alkyl and N,N-dialkylaminomethanesulfonic acids were synthesized (as zwitterions and/or sodium salts) to be tested for utility as biological buffers at lower pH levels than existing Good buffer compounds (aminoalkanesulfonates with a minimum of two carbons between amine and sulfonic acid groups as originally described by Norman Good, and in common use as biological buffers). Our hypothesis was that a shorter carbon chain (one carbon) between the amino and sulfonic acid groups should lower the ammonium ion pK(a) values. The alkylaminomethanesulfonate compounds were synthesized in aqueous solution by reaction of primary or secondary amines with formaldehyde/sodium hydrogensulfite addition compound. The pK(a) values of the ammonium ions of this series of compounds (compared to existing Good buffers) was found to correlate well with the length of the carbon chain between the amino and sulfonate moeties, with a significant decrease in amine basicity in the aminomethanesulfonate compounds (pK(a) decrease of 2 units or more compared to existing Good buffers). An exception was found for the 2-hydroxypiperazine series which shows only a small pK(a) decrease, probably due to the site of protonation in this compound (as confirmed by X-ray crystal structure). X-ray crystallographic structures of two members of the series are reported. Several of these compounds have pK(a) values that would indicate potential utility for buffering at pH levels below the normal physiological range (pK(a) values in the range of 3 to 6 without aqueous solubility problems)- a range that is problematic for currently available Good buffers. Unfortunately, the alkylaminomethanesulfonates were found to degrade (with loss of their buffering ability) at pH levels below the pK(a) value and were unstable at elevated temperature (as when autoclaving)- thus limiting their utility.

The development of a new method for the stereoselective synthesis of alpha-2-deoxy-2-amino glycosides is described. This methodology relies on the nature of the cationic nickel catalyst, generated in situ from L(n)NiCl(2) and AgOTf, to direct the anomeric stereoselectivity. The new glycosylation reaction is highly alpha-selective and proceeds under mild conditions with 5-10 mol % of the nickel catalyst loading at ambient temperature. This new method has been applied to both d-glucosamine and galactosamine trichloroacetimidate donors as well as an array of primary, secondary, and tertiary alcohol nucleophiles to provide the desired glycoconjugates in good yields with excellent alpha-selectivity. Mechanistic studies of the present reaction are underway and will be reported in due course.

The development of a new glycosylation method for the stereoselective synthesis of beta-glycosides in the absence of the traditional C(2)-ester neighboring group effect is described. This process relies on the ability of the cationic palladium catalyst, Pd(PhCN)(2)(OTf)(2) generated in situ from Pd(PhCN)(2)Cl(2) and AgOTf, to direct beta-selectivity. The new glycosylation reaction is highly beta-selective and proceeds under mild conditions with 1-2 mol % of catalyst loading. This beta-glycosylation method has been applied to a number of glucose donors with benzyl, allyl, and p-methoxybenzyl groups incorporated at the C(2)-position as well as tribenzylated xylose and quinovose donors to prepare various disaccharides and trisaccharides with good to excellent beta-selectivity. Mechanistic studies suggest that the major operative pathway is likely to proceed via a seven-membered ring intermediate, wherein the cationic palladium complex coordinates to both the C(1)-imidate nitrogen and C(2)-oxygen of the trichloroacetimidate donor. Formation of this seven-membered ring intermediate directs the selectivity, leading to the formation of beta-glycosides.

Type II pneumocytes in newborn lungs are more uniformly distributed, whereas in adult lungs they are located at alveolar corners. We used morphometry and reverse transcription-polymerase chain reaction in situ hybridization of surfactant protein C mRNA to determine the patterns of type II cell distribution in random lung sections from Sprague-Dawley rats at various neonatal stages and adults. There was a progressive increase in the percentage of type II cells at alveolar corners from 30% at 1 day to 51, 62, 78, and 81% at 3, 5, and 7 days old and adult rats, respectively. There were statistically significant differences (P < 0.001) in the localization of type II cells from the nearest alveolar corner in the 1-day-old compared with 7-day-old and adult rat lungs. These results show that rat type II cells localize to the alveolar corners within the first 7 days postnatally and provide a system for study of factors that regulate alveolar epithelial cell distribution.