Esters of crotonic acid were brominated on a multigramme scale using a free radical procedure. A phase transfer catalysed fluorination transformed these species to the 4-fluorobut-2E-enoates reproducibly and at scale (48-53%, ca. 300 mmol). Asymmetric dihydroxylation reactions were then used to transform the butenoate, ultimately into all four diastereoisomers of a versatile fluorinated C4 buil...

After i.v. administration of d,l-, 1-5-formyltetrahydrofolate (d,l-CHO-THF) CHO-THF was rapidly cleared from the plasma by conversion to 5-methyltetrahydrofolate (5-CH3-THF) and urinary excretion, whereas d-CHO-THF, which was not metabolized and was slowly excreted in the urine, persisted in plasma at concentrations greatly exceeding those of l-CHO-THF and 5-CH3-THF. The plasma half-life (beta)...

The pharmacokinetics of dand /-Citrovorum factor (CF) are quite different with respect to the postdistributional plasma decay rates. The natural (/) isomer had a half-life (/?) of 47 ±4 (S.E.) min compared to 143 ± 15 min for the unnatural (d) isomer. Renal clearance was the same for both isomers and was proportional to glomerular filtration rate. Urinary excretion appeared to be the only rou...

The pharmacokinetics of d- and l-citrovorum factor (CF) are quite different with respect to the postdistributional plasma decay rates. The natural (l) isomer had a half-life (beta) of 47 +/- 4 (S.E.) min compared to 143 +/- 15 min for the unnatural (d) isomer. Renal clearance was the same for both isomers and was proportional to glomerular filtration rate. Urinary excretion appeared to be the o...

Chemical methods for the synthesis of short deoxyribooligonucleotides containing methyl and phenylphosphonodiester linkages have been developed. The interaction of two such nonionic dinucleotide analogs, T(pCH3)T and T(pC6H5)T, with several enzymes has been investigated. Because of the phosphonate linkage each dinucleotide exists as a diastereomeric pair as shown by thin layer chromatography an...

The primary quorum sensing system in the opportunistic pathogen Pseudomonas aeruginosa is regulated through the synthesis and secretion of N-3-oxo-dodecanoyl-L-homoserine lactone (C12) which binds the transcriptional activator LasR. In this study we report the design, synthesis and biological evaluation of new analogs of C12. Analysis of the autoinducer binding site cavity of LasR revealed a po...