Total syntheses of schulzeines B and C

Schulzeines B (2) and C (3) were synthesized by a convergent strategy using epimeric tricyclic lactam building blocks, 4 and 5, and the C28 fatty acid side chain 6. Syntheses of tricyclic lactams (4/5) were achieved by Bischler-Napieralski reaction. Sharpless asymmetric dihydroxylation and BINAL-H-mediated asymmetric reduction of an enone was employed to prepare the key fatty acid side chain 6. The spectral as well as analytical data of 2 and 3 were in good agreement with the reported data for the natural products, thus confirming their assigned structures

Synthesis and enzymatic evaluation of ketose phosphonates: the interplay between mutarotation, monofluorination and acidity

Ketose-phosphonates may adopt open chain, or \u3b1- or \u3b2-furanosyl, or \u3b1- or \u3b2-pyranosyl configurational isomers in aqueous solution. An HPLC and NMR analysis of a series of ketose-phosphonates with a thymidylyltransferase (dTDP-glucose pyrophosphorylase) implied a rapid dynamic equilibrium between the pyranosyl forms of gluco-ketose phosphonate leading to efficient production of unique sugar nucleotide analogues. The preparation of diastereomerically pure gluco-configured monofluoromethylenephosphonates enabled the determination of the thymidylyltransferase preference for CHF stereochemistry. The effects of acidity upon thymidylyltransferase substrate specificity were determined using a series of monofluoro- and difluoro- ketose-phosphonates. WaterLOGSY NMR spectroscopy demonstrated a switching of the ordered Bi-Bi mechanism with ketose-phosphonate substrates. Ketose-phosphonates are presented as a unique class of sugar 1-phosphate analogues with potential applications as glycosyltransferase probes.Peer reviewed: YesNRC publication: Ye

α-Fluorophosphonates reveal how a phosphomutase conserves transition state conformation over hexose recognition in its two-step reaction.

β-Phosphoglucomutase (βPGM) catalyzes isomerization of β-d-glucose 1-phosphate (βG1P) into d-glucose 6-phosphate (G6P) via sequential phosphoryl transfer steps using a β-d-glucose 1,6-bisphosphate (βG16BP) intermediate. Synthetic fluoromethylenephosphonate and methylenephosphonate analogs of βG1P deliver novel step 1 transition state analog (TSA) complexes for βPGM, incorporating trifluoromagnesate and tetrafluoroaluminate surrogates of the phosphoryl group. Within an invariant protein conformation, the β-d-glucopyranose ring in the βG1P TSA complexes (step 1) is flipped over and shifted relative to the G6P TSA complexes (step 2). Its equatorial hydroxyl groups are hydrogen-bonded directly to the enzyme rather than indirectly via water molecules as in step 2. The (C)O–P bond orientation for binding the phosphate in the inert phosphate site differs by ∼30° between steps 1 and 2. By contrast, the orientations for the axial O–Mg–O alignment for the TSA of the phosphoryl group in the catalytic site differ by only ∼5°, and the atoms representing the five phosphorus-bonded oxygens in the two transition states (TSs) are virtually superimposable. The conformation of βG16BP in step 1 does not fit into the same invariant active site for step 2 by simple positional interchange of the phosphates: the TS alignment is achieved by conformational change of the hexose rather than the protein