Robin G. F. Giles

Rhizobium leguminosarum bv. viciae produces a novel cyclic trihydroxamate siderophore, vicibactin

Trihydroxamate siderophores were isolated from iron-deficient cultures of three strains of Rhizobium leguminosarum biovar viciae, two from Japan (WSM709, WSM710) and one from the Mediterranean (WU235), and from a Tn5-induced mutant of WSM710 (MNF7101). The first three all produced the same compound (vicibactin), which was uncharged and could be purified by solvent extraction into benzyl alcohol. The gallium and ferric complexes of vicibactin were extractable into benzyl alcohol at pH 5.0, while metal-free vicibactin could be extracted with good yield at pH 8.0. The trihydroxamate from MNF7101 (vicibactin 7101) could not be extracted into benzyl alcohol, but its cationic nature permitted purification by chromatography on Sephadex CM-25 (NH+4 form). Relative molecular masses and empirical formulae were obtained from fast-atom-bombardment MS. The structures were derived from one- and two-dimensional 1H and 13C NMR spectroscopy, using DQF-COSY, NOESY, HMQC and HMBC techniques on the compounds dissolved in methanol-d4 and DMSO-d6. Vicibactin proves to be a cyclic molecule containing three residues each of (R)-2,5-diamino-N2-acetyl-N 5-hydroxypentanoic acid (N2-acetyl-N5-hydroxy-D-ornithine) and (R)-3-hydroxybutanoic acid, arranged alternately, with alternating ester and peptide bonds. Vicibactin 7101 differed only in lacking the acetyl substitution on the N2 of the N5-hydroxyornithine, resulting in net positive charge; it was still functional as a siderophore and promoted 55Fe uptake by iron-starved cells of WSM710 in the presence of an excess of phosphate. The rate of vicibactin biosynthesis by iron-deficient cells of WSM710 was essentially constant between pH 5.5 and 7.0, but much decreased at pH 5.0. When iron-starved cultures were supplemented with potential precursors for vicibactin, the rates of its synthesis were consistent with both β-hydroxybutyrate and ornithine being precursors. At least three genes seem likely to be involved in synthesis of vicibactin from ornithine and β-hydroxybutyrate: a hydroxylase adding the -OH group to the N5 of ornithine, an acetylase adding the acetyl group to the N2 of ornithine, and a peptide synthetase system.

Isochromenes and their quinones through cyclisations with bisacetonitriledichloropalladium(II)

Bisacetonitriledichloropalladium(II) is found to cyclise ortho-alkenylbenzyl alcohols rapidly to the corresponding isochromenes. The reaction also proceeds rapidly for a 2-allyl-3-hydroxyalkyl-1,4-naphthoquinone, when the product is a benzoisochromenequinone.

Stereoselective isomerisations of 4-(3′,5′-dimethoxyphenyl)-2,5-dimethyl-1,3-dioxolanes. Temperature-dependent formation of either isochromanes or dihydroisobenzofurans

Stereoselective isomerisation of rel-(2R,4S,5R)-4-(3′,5′-dimethoxyphenyl)-2,5-dimethyl-1,3-dioxolane 7 with titanium tetrachloride affords rel-(1R,3R,4S)-4-hydroxy-6,8-dimethoxy-1,3-dimethylisochromane 19 and its C-1 epimer 20 in high yield. The former predominates at a reaction temperature of –78 °C and the latter at –30 °C. Similar isomerisation of the 1 : 1 mixture of rel-(2S,4R,5R)- and rel-(2S,4R,5R)-4-(3′,5′-dimethoxyphenyl)-2,5-dimethyl-1,3-dioxolanes 8 and 9 gives rel-(1R,3R,4R)-4-hydroxy-6,8-dimethoxy-1,3-dimethylisochromane 29 and its C-1 epimer 31, with the latter predominating at both –78 and –30 °C. At 0 °C, dioxolane 7 is isomerised to rel-(1S,1′R,3R)-1-(1′-hydroxyethyl)-4,6-dimethoxy-3-methyl-1,3-dihydroisobenzofuran 25 and its C-3 epimer 26 as the sole reaction products in a 10 : 1 ratio. Dioxolanes 8 and 9 are similarly converted into rel-(1R,1′R,3S)-1-(1′-hydroxyethyl)-4,6-dimethoxy-3-methyl-1,3-dihydroisobenzofuran 32 and its C-3 epimer 33. These furans probably arise through further isomerisation of the intermediate isochromanes at the higher reaction temperatures.

Towards the synthesis of chiral isochromanquinones. The use of Corey–Bakshi–Shibata reductions

(1R,3R,4S)-3,4-Dihydro-4-hydroxy-6-methoxy-1,3-dimethylisochroman-5,8-dione has been synthesized in 65% ee from (1R,3R,4S)-5-benzyloxy-3,4-dihydro-4-hydroxy-6-methoxy-1,3-dimethylisochroman by catalytic hydrogenolysis followed by Fremys salt oxidation of the derived phenol. The latter isochroman was synthesized from a mercury(II) mediated oxidative cyclization of (R)-3-benzyloxy-4-methoxy-1-(1′-hydroxyethyl)-2-prop-1′-enylbenzene which in turn was obtained in 75% ee from the chiral reduction of 1-acetyl-3-benzyloxy-4-methoxy-2-prop-1′-enylbenzene with borane–methylsulfide complex in the presence of the Corey–Bakshi–Shibata catalyst.

A HIGH YIELDING SYNTHESIS OF RACEMIC HONGCONIN

Racemic hongconin 1 has been synthesized from adduct 2 formed by reaction between 1-methoxycyclohexa-1,4-diene and benzoquinone. The synthetic strategy includes Fries and Claisen rearrangements, base and cerium(IV) initiated pyran ring formation, C-4 pyran ring hydroxylation and silver(II) mediated oxidation.

Naphtho[2,3-c]pyran-5,10-quinones. Syntheses of the racemates of quinone A, quinone A′, and deoxyquinone A dimethyl ethers of 7-methoxyeleutherin, and of isoeleutherin

Treatment of 3-(1-hydroxyethyl)-1,4,5,7-tetrarmethoxy-2-prop-2-enylnaphthalene (33) with potassium t-butoxide in dimethylformamide under nitrogen for a short time gave a high yield of trans-3,4-dihydro-5,7,9,10-tetramethoxy-1,3-dimethyl-1H-naphtho[2,3-c]pyran (41). This compound, with the same base and solvent, but in air, afforded a mixture comprising its cis-epimer (42), together with the two possible 4-hydroxy derivatives, namely (35) and (38). Silver(II) oxide oxidation of compounds (35), (38), (41), and (42) gave, respectively, the dimethyl ethers of quinone A, quinone A′, and deoxyquinone A, and also 7-methoxyeleutherin.

Synthesis of new semi-rigid chelating agents for samarium-153

This study describes a simple, efficient synthesis pathway from trans-1,2-diaminocyclohexane that provides access to a new class of semi-rigid polyamine, polycarboxylic, and polyphosphonic ligands. The key steps in synthesis were the functionalisation (with an appropriate branching group) of a bisphosphonate diaminocyclohexane derivative and the introduction of methanephosphonic functions by a rarely used method.

The syntheses of (±)-juglomycin A and (±)-juglomycin B, racemates of two isomeric naturally occurring naphthoquinonoid antibiotics

Syntheses of the diastereoisomeric 5-hydroxy-2-(4′-hydroxy-γ-butyrolacton-5′-yl)-1,4-naphthoquinones (1) and (2) and their 5-deoxy-analogues (3) and (4) are described. The stereochemistries of the latter, being defined through unambiguous synthesis, permit the assignment of the configurations of (1) and (2)(which were obtained from a single precursor) and also those of the natural products, juglomycins A and B.

Synthesis of Methoxy‐2‐hydroxy‐1,4‐naphthoquinones and Reaction of One Isomer with Aldehydes Under Basic Conditions

Abstract Two protocols for the synthesis of methoxy‐2‐hydroxy‐1,4‐naphthoquinones were investigated in order to evaluate their behavior towards aldehydes under amine‐basic conditions. Both the nature of the quinone and aliphatic aldehyde contribute to the viability of this condensation as well as further transformations.

Base-induced cyclisations of naphthalenes into naphtho[2,3-c]pyrans. Application to stereospecific syntheses of (±)-isoeleutherin and (±)-deoxyquinone a dimethyl ether

2-(Alk-2-enyl)-3-(1-hydroxyalkyl)-1,4-dimethoxynaphthalenes are cyclised and then oxidised to naphtho[2,3-c]pyran-5,10-quinones which are naturally occurring quinones or their derivatives.