Colin C. Howard

Isolation of brefeldin a from Phyllosticta medicaginis

Abstract Cultivation of the fungus, Phyllosticta medicaginis , afforded good yields of brefeldin A, mannitol, and fatty-acid glycerides as the principle metabolites. The fatty-acid content of the glycerides was determined.

Factors governing the ratio of isomeric oxabicyclo[3.2.1]octanones formed on Baeyer–Villiger oxidation of some 5-endo,7-anti-disubstituted bicyclo[2.2.1]heptan-2-ones

It was found that the outcome of Baeyer–Villiger oxidation of 5-endo,7-anti-disubstituted bicyclo[2.2.1]heptan-2-ones was influenced by at least three factors: (i) the electronegativity of the substituent at C-7; (ii) the hydrogen-bonding capability of the substituent at C-5; and (iii) the peracid employed. The optimum substituents and reaction conditions for oxidation of a bicycloheptanone to the corresponding 2-oxabicyclo[3.2.1]octan-3-one were delineated and used in the synthesis of a prostaglandin intermediate.

Fungal metabolites. Part III. Isolation of secalonic acids fromPhoma terrestris

Extraction of the dried mycelium of Phoma terrestris Hansen gave two yellow pigments to which are assigned the substituted 9,9′-dioxo-2,2′-bixanthen-10a,10a′-dicarboxylate structures (1a) and (2a). Compound (1a) has not been reported previously and we designate this secalonic acid E, although it appears to be enantiomeric with secalonic acid B. Compound (2a) has a structure already assigned to secalonic acid A but differs from the latter in some analytical details; reasons for these differences are suggested.

Total synthesis of (±)-prostaglandin E2 methyl ester from exo-2-bromo-endo-3-hydroxybicyclo[3.2.0]heptan-6-one using dimethyl-t-butylsilyl protected intermediates

Peracetic acid oxidation at –78 °C of the dihydroxybicyclo[3.2.0]heptan-6-one (23) afforded the dihydroxylactone (24) which was protected as its bisdimethyl-t-butylsilyl ether (26) and reduced to the corresponding lactol (27). A Wittig reaction on (27), carried out in benzene with a short reaction time, gave mainly the required 11α-silyl ether (28) together with a trace of the 9α-silyl ether (29) which results from 1,5-migration of the silyl group. Oxidation of (28) followed by quantitative deprotection using aqueous HF in acetonitrile afforded (±)-PGE2 methyl ester (20). This short stereo-and regio-selective total synthesis proceeds in an overall yield of 10% starting from cyclopentadiene.

Fungal metabolites. Part I. Stereochemical features and mass spectrometry of secalonic acids

The mass spectra of secalonic acids A, C, D, E(B)(dimethyl 5,5′,6,6′,7,7′,10a,10a′-octahydro-1,1′ 5, 5′,8,8′-hexa-hydroxy-6,6′-dimethyl-9,9′-dioxo-2,2′-bixanthen-10a,10a′-dicarboxylates) show features closely related to the stereochemistry at the six chiral centres in these compounds. Analysis of the spectra suggests that the stereochemistry of any new secalonic acid could be defined largely by its mass spectrum.

Total synthesis of prostaglandin-F2α involving stereocontrolled and photo-induced reactions of bicyclo[3.2.0]heptanones

Das Bicycloheptenon (I) liefert mit dem Dibromdimethylhydantoin (II) das Ketobromhydrin (III), dessen Acetal (IV) mit Namethylat das Epoxid (V) gibt.

Regioselective reactions of 2,3-endo-epoxybicyclo[3.2.0]heptanone ethylene acetal involving organometallic reagents

The preparation of (1′,α,2′α,4′α,6′α)-spiro{[1,3]dioxolan-2,7′-[3′]oxatricyclo[4.2.0.02′,4′]octane}(3) and its reaction with various organometallic reagents is described. Attack occurred at C-2 preferentially (selectivity 67–83%) due to the influence of the neighbouring cyclobutane ring on the relative energies of the transition states leading to epoxy-ring opening. The conformation of the bicyclo[3.2.0]heptane system in the products is discussed.

Fungal metabolites. Part VI. Crystal and molecular structure of secalonic acid A

X-Ray analysis of secalonic acid A (C32H30O14,2CH3CO2H) has confirmed the 2,2′-nature of the biphenyl linkage between the two halves of the molecule. Together with the known stereochemistry at C(6), C(6′)(I), this provides the absolute configuration of the molecule. The analysis has also indicated how the acetic acid molecules are incorporated in the crystal structure by hydrogen bonding. Estimation by n.m.r. of the torsion angle between adjacent C–OH and C–Me groups in secalonic acid A from solvent-induced changes of chemical shift was confirmed by the X-ray results.

Fungal metabolites. Part IV. Solvent and transition metal effects on proton chemical shifts in multifunctional molecules

During attempts to define the stereochemistry of secalonic acids isolated from fungi, we made use of a europium shift reagent and were able to define the major complexing sites in these multifunctional compounds. However, we also observed changes in the chemical shifts of protons near hydroxy-groups in the secalonic acids simply on change of solvent. From an examination of the 1H n.m.r. spectra of sterols, terpenols, other alcohols, and phenols, we have been able to propose a relationship between the amount by which the chemical shift of a proton moves on change of solvent and the distance of the proton from a hydroxy-group. The relationship can be used to determine the torsional angle between a methyl and a hydroxy-group situated in a 1,2-relationship. In multifunctional compounds, these solvent-induced changes can be influenced by other groups close to the proton considered.

Use of differential solvent shifts in nuclear magnetic resonance

In compounds containing a methyl group β to a hydroxy-group, an estimate of the dihedral angle between them can be obtained by measurement of the chemical shift of the methyl group in the solvent pairs dimethyl sulphoxide–pyridine or deuteriochloroform–pyridine; quinoline is also suggested as a solvent for use in such studies.