933992-79-1Relevant academic research and scientific papers
Marked small molecule libraries: A truncated approach to molecular probe design
Inverarity, Iain A.,Hulme, Alison N.
, p. 636 - 643 (2007)
A truncated approach to the design of molecular probes from small molecule libraries is outlined, based upon the incorporation of a bioorthogonal marker. The applicability of this strategy to small molecule chemical genetics screens has been demonstrated using analogues of the known stress activated protein kinase (SAPK) pathway activator, anisomycin. Compounds marked with a propargyl group have shown activation of the SAPK pathways comparable to that induced by their parent structures, as demonstrated by immunoblot assays against the downstream target JNK1/2. The considerable advantages of this new approach to molecular probe design have been illustrated through the rapid development of a functionally active fluorescent molecular probe, through coupling of the marked analogues to fluorescent azides using the copper(i)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction. Active molecular probes generated in this study were used to investigate cellular uptake through FACS analysis and confocal microscopy. This journal is The Royal Society of Chemistry.
A New Synthesis of (-)-Anisomycin and its Demethoxy analogue from D-Ribose
Buchanan, J. Grant,MacLean, Keith A.,Wightman, Richard H.,Paulsen, Hans
, p. 1463 - 1470 (2007/10/02)
2,3-O-Isopropylidene-D-ribose (7) reacted with p-methoxybenzylmagnesium chloride in tetrahydrofuran to give the D-allotriol (6a) (77percent).Periodate oxidation of compound (6a) followed by reaction with hydroxylamine hydrochloride in pyridine gave (E,Z)-5-deoxy-2,3-O-isopropylidene-5-(p-methoxyphenyl)-L-ribose oxime (18a) which was converted into the nitrile methanesulphonate (19a) with methanesulphonyl chloride in pyridine.Reduction of the nitrile (19a) with lithium aluminium hydride gave (2R,3S,4R)-3,4-isopropylidenedioxy-2-(p-methoxybenzyl)pyrrolidine (2a) , which was converted into the epoxide (24a) (68percent) via the bromo acetates (28a) and (29a).Regioselective opening of the epoxide ring in compound (24a) with acidic allyl alcohol gave the allyl ether (30a) (63percent) which was converted into the N-benzyl 3-acetoxy compound (31a) (77percent).Removal of the allyl and benzyl groups, by treatment with palladium-charcoal under acidic conditions followed by hydrogenolysis, gave (-)-anisomycin (1a (86percent). A similar series of reactions afforded demethoxyanisomycin (1b) which showed antibiotic activity against Trichomonas vaginalis .
