Synthetic studies with carbohydrate-derived chiral auxiliaries

Since the late 1950’s when proton n. m. r. spectroscopy was first used in organic natural products studies the technique has increasingly contributed to the rapid advancement of this important area of chemistry. Although the potential utility of 13C n. m. r. was recognized very early, essentially no application of 13C n. m. r. appeared in the literature prior to 1966 and 95% of the existing data are less than five years old. The initially slow growth had its cause in inadequate instrumentation, insufficient sensitivity being the main obstacle. This situation drastically changed with the advent and commercial availability of broadband excitation and Fourier transform methods, giving natural-abundance 13C n. m. r. and its numerous chemical applications a tremendous impetus. Today 13C spectra can be recorded on sample quantities down to the submilligram level, which until recently even withstood proton n. m. r.

The Use of Carbon-13 Nuclear Magnetic Resonance Spectroscopy in Natural Products Chemistry

Practical radical cyclisations leading to the construction of near-stereopure quaternary carbon stereogenic centres

Tunable Forster resonance energy transfer (FRET)-quenched substrates are useful for monitoring the activity of various enzymes within their relevant physiological environments. Development of FRET-quenched substrates for exo-glycosidases, however, has been hindered by their constrained pocket-shaped active sites. Here we report the design of a new class of substrate that overcomes this problem. These Bis-Acetal-Based Substrates (BABS) bear a hemiacetal aglycon leaving group that tethers fluorochromes in close proximity, also positioning them distant from the active site pocket. Following cleavage of the glycosidic bond, the liberated hemiacetal spontaneously breaks down, leading to separation of the fluorophore and quencher. We detail the synthesis and characterization of GlcNAc-BABS, revealing a striking 99.9% quenching efficiency. These substrates are efficiently turned over by the human exo-glycosidase O-GlcNAcase (OGA). We find the hemiacetal leaving group rapidly breaks down, enabling quantitative mo...

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Carbohydrate Bis-acetal-Based Substrates as Tunable Fluorescence-Quenched Probes for Monitoring exo-Glycosidase Activity.

2.22 – Pyrans and Fused Pyrans: (i) Structure

Regio- and stereo-selective bromoalkoxylations of carbonyl compounds: a route to stereopure α-bromo-α-dioxymethyl carbonyl compounds

(E)-4-Methoxymethoxy-3-methylbut-3-en-2-one 17b reacts with NBS in propan-1-ol in a highly regio- and anti-stereo-selective manner to give (3R*,4R*)-3-bromo-4-methoxymethoxy-3-methyl-4-propoxybutan-2-one 18. Compound 10, a relative of the butenone 17b in which the methoxymethyl group is replaced by the 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl unit, undergoes an analogous bromo(propoxylation) reaction with reasonable facial selectivity to give an 86∶14 mixture of (3R,4R)-3-bromo-3-methyl-4-propoxy-4-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyloxy)butan-2-one 11c and its (3S,4S)-diastereomer 12c. The major bromo(propoxy) derivative, isolable in 57% yield by fractional crystallisation, is assigned the stereostructure 11c by single-crystal X-ray crystallographic analysis. Other primary alcohols and methanol participate in the reaction of compound 10 with NBS, leading predominantly (with selectivities ranging from 75∶25 to 89∶11) to bromo(alkoxy) products of type 11 which are usually separable from their diastereomers of type 12 by fractional crystallisation (in yields ranging from 41 to 64%). A model to account for the role of the 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl unit in the stereoinduction process is proposed.
 Related bromo(propoxylation)s are observed with the vinylogous esters 24, 25a and 25b, leading to the isolation of the major products, 28, 30a and 30b (in yields ranging from 39 to 55%), and with the vinylogous carbonates 32a, 32c, 37a and 37b, providing access to the major products 33a, 33c, 38a and 38b (in yields ranging from 52 to 73%).
 In the presence of trifluoroacetic acid and ethane-1,2-diol, the bromo(propoxy) derivatives 11c, 28, 30b and 33c undergo transacetalisation to give the ethylene glycol acetals 40a, 40b, 41 and 40c with ees of 94–98%, in yields ranging from 56 to 67%.
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Regio- and stereo-selective bromo(alkoxylation)s of (E)-α-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxymethylene) carbonyl compounds. A route to near-stereopure α-bromo α-dioxymethyl carbonyl compounds

The synthesis of the dialdehyde 1-hydroxy-3,6,7-trimethoxy-2,8-bis-(2-oxoethyl)xanthone, first obtained from ozonolysis of dimethylmangostin, is described. Xanthone formation by cyclisation of a benzophenone intermediate is followed by selective demethylations, allylation, and Claisen rearrangement. Oxidative cleavage of the allyl side chains in 2,8-diallyl-1,3,6,7-tetramethoxyxanthone, followed by demethylation with boron trichloride, gave the required dialdehyde (5). Some 13C n.m.r. spectra of xanthones are discussed.

Extractives from Guttiferae. Part 33. Synthesis of the ozonolysis product from dimethylmangostin, 1-hydroxy-3,6,7-trimethoxy-2,8-bis-(2-oxoethyl)xanthone; some 13C nuclear magnetic resonance spectra of xanthones

Regio- and Stereoselective Bromo(alkoxylation)s of (E)-α- (2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyloxymethylene) Carbonyl Compounds. A Route to Near-Stereopure α-Bromo α-Dioxymethyl Carbonyl Compounds.

M. Sum Idris

Papers

Regio- and stereo-selective bromoalkoxylations of carbonyl compounds: a route to stereopure α-bromo-α-dioxymethyl carbonyl compounds

Regio- and stereo-selective bromo(alkoxylation)s of (E)-α-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxymethylene) carbonyl compounds. A route to near-stereopure α-bromo α-dioxymethyl carbonyl compounds

Extractives from Guttiferae. Part 33. Synthesis of the ozonolysis product from dimethylmangostin, 1-hydroxy-3,6,7-trimethoxy-2,8-bis-(2-oxoethyl)xanthone; some 13C nuclear magnetic resonance spectra of xanthones

Regio- and Stereoselective Bromo(alkoxylation)s of (E)-α- (2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyloxymethylene) Carbonyl Compounds. A Route to Near-Stereopure α-Bromo α-Dioxymethyl Carbonyl Compounds.