Frans Compernolle

Trihydroxycoprostanic acid in the duodenal fluid of two children with intrahepatic bile duct anomalies

Abstract Using thin-layer chromatography, gas-liquid chromatography and mass spectrometry, trihydroxycoprostanic acid (3α, 7α, 12α-trihydroxy-5β-cholestan-26-oic acid) was identified in the duodenal fluid of 2 subjects with anomalies of the intrahepatic bile ducts. Sugject I was a case of intrahepatic cholestasis due to atresia of the interlobular bile ducts with familial incidence. The bile acid spectrum in the duodenal fluid of this patient was: 23% chenodeoxycholic acid, 58% cholic acid and 19% trihydroxycoprostanic acid. Subject 2 had a Zellweger-like syndrome with cholestasis and with scarely developed intrahepatic bile ductuli. The bile acid spectrum in the duodenal fluid of this patient was: 18% chenodeoxycholic acid, 37% cholic acid and 45% trihydroxycoprostanic acid. No trihydroxycoprostanic acid was found in seven healthy subjects, in three cases of cholestasis of infancy, or in ten cases of various disorders of the small intestine. Obviously, the excretion of trihydroxycoprostanic acid with the bile of Patients 1 and 2 was due to a reduced capacity of the hepatocytes to split off the 3 terminal carbon atoms of the side chain of trihydroxyprostanic acid. The cause of the impaired function of the hepatocytes remains to be established.

Biosynthesis of the diterpenoid steviol, an ent-kaurene derivative from Stevia rebaudiana Bertoni, via the methylerythritol phosphate pathway

Abstract As shown from [1- 13 C]glucose incorporation, steviol, the diterpene aglycone moiety of stevioside, is synthesized in Stevia rebaudiana Bertoni via the mevalonate-independent methylerythritol phosphate pathway.

Synthesis of cis-fused hexahydro-4aH-indeno[1,2-b]pyridines via intramolecular Ritter reaction and their conversion into tricyclic analogues of NK-1 and dopamine receptor ligands

Abstract Indanol intermediates prepared via Michael addition of 1-indanone β-ketoester and acrylonitrile, followed by Grignard reaction of the ketone group, were submitted to an intramolecular Ritter reaction to produce cis-fused methyl 2-oxo-9b-phenyl-1,2,3,4,5,9b-hexahydro-4aH-indeno[1,2-b]pyridine-4a-carboxylates with 4a,9b-diangular substitution pattern. Further transformation of the bridgehead ester group and the lactam function afforded constrained tricyclic analogues of some monocyclic piperidine NK-1 antagonists and of a bicyclic dopamine receptor ligand.

Identification of the oxidation products of the reaction between α-pinene and hydroxyl radicals by gas and high-performance liquid chromatography with mass spectrometric detection

In this paper an identification method is described for determining the degradation products of the reaction of alpha-pinene with hydroxyl radicals. The study is carried out in a fast-flow reactor equipped with a specially designed microwave cavity (type Surfatron) allowing to operate at pressures up to 100 Torr (1 Torr=133.322 Pa). The semivolatile products are collected on a liquid nitrogen trap (LN2 trap) and the batch samples are subsequently analysed by GC-MS and HPLC-MS. Some samples were also collected directly on a LpDNPH-cartridge, followed by HPLC-MS analysis. When experiments were carried out at 50 Torr both GC-MS and HPLC-MS measurements showed that campholenealdehyde and pinonaldehyde were identified as condensable oxidation products for the alpha-pinene/OH reaction, with pinonaldehyde being the main product. Furthermore, the LN2 trap collection method based on the in situ conversion of aldehydes and ketones to their 2,4-dinitrophenylhydrazone derivatives allowed the determination of formaldehyde, acetaldehyde and acetone. Although formaldehyde and acetone are present in small amounts in blank samples it could be established that formaldehyde and acetone are also formed in the alpha-pinene/OH reaction.

Diels-Alder reactions of pyridine o-quinodimethane analogues generated from functionalised o-bis(chloromethyl)pyridines☆

Abstract The polyfunctional 2,3- and 3,4-o-bis(chloromethyl)pyridines 3, produced via cycloaddition of the oxazinones 2 with propargyl chloride and 1,4-dichloro-2-butyne, were used as precursors of various pyridine o-quinodimethane analogues. The 2,3- and 3,4-dimethylenepyridine systems were generated via reductive 1,4-elimination with iodide and trapped in situ with various dienophiles to form the tetrahydroquinoline and -isoquinoline type adducts. A regiospecific cycloaddition was observed for the 3,4-dimethylenepyridine system with electron-rich dienophiles, i.e. dihydrofuran and ethyl vinyl ether, in contrast to the reaction with methyl acrylate.

Cycloadducts of ethene with 2(1H)-pyrazinones and their conversion into 2,5-diazabicyclo[2.2.2]octane-3,6-diones.

Abstract Cycloaddition of variously substituted 2(1H)-pyrazinones with ethene and subsequent hydrolysis of the adducts 2 provides a general and efficient route to the title compounds 3. Compound 3m was used as a building block for a structural analogue of gliotoxin.

Synthesis of 1-deoxymannojirimycin analogues using N-tosyl and N-nosyl activated aziridines derived from 1-amino-1-deoxyglucitol

Abstract 3,4;5,6-Diisopropylidene protected 1-amino-1-deoxy- d -glucitol was transformed into N -tosyl and N -nosyl activated aziridine intermediates, which underwent ring opening by reaction with various nucleophiles. The 5,6-diols resulting from selective hydrolysis of the terminal acetal group were subjected to (2-N→6-OH) cyclisation using two different methods for activation of 6-OH. Final deprotection of the N -nosyl and 3,4-acetal group proceeded smoothly to afford 6-substituted analogues of 1-deoxymannojirimycin.

Cannabiorci- and 8-chlorocannabiorcichromenic acid as fungal antagonists from Cylindrocarpon olidum

Cannabiorcichromenic acid and 8-chlorocannabiorcichromenic acid [8-chloro-5-hydroxy-2,7-dimethyl-2-(4-methyl-3-pentenyl)-2H-1-benzopyran -6- carboxylic acid] were identified as active components in cultures of Cylindrocarpon olidum which antagonized various other fungi. Experiments performed with the purified acids confirmed the antifungal activity; in addition, they revealed that the acids had antibiotic properties towards gram-positive bacteria and were toxic to nematodes.

The synthesis of 6-azido and 6-amino analogues of 1-deoxynojirimycin and their conversion to bicyclic derivatives

Abstract 1-Amino-1-deoxy- d -glucitol (14) was converted to the N-Boc-2,3;5,6-di-O-isopropylidene derivative 16 which was transformed further into the selectively protected 2,3-O-isopropylidene 6-azido piperidine 3. The synthesis proceeded via a double inversion at C-5 involving internal attack of 4-OH to form the 4,5-epoxide 28, and ring opening of this epoxide by 1-NH2 to generate the piperidine 3. This served as a valuable precursor of various target compounds, i.e. 6-azido- and 6-amino-1,6-dideoxynojirimycin 4 and 5, and the mono- and bicyclic derivatives 6–12.

Functionalized o-bis(chloromethyl)pyridines as precursors for pyridine o-quinodimethane analogues and their [4+2] cycloadducts

Abstract From oxazinones 4 , precursors for pyridine o-quinodimethane analogues are made accessible via cycloaddition with 1,4-dichloro-2-butyne and propargyl chloride. Subsequent 1,4-elimination of the polyfunctional o-bis(chloromethyl)-pyridines affords both 2,3- and 3,4-dimethylene compounds, which are trapped in situ with various dienophiles.