The structure of the major urinary metabolite of prostaglandin E2 in man

This letter reports the structure of the major urinary metabolite formed from prostaglandin E2 (PGE2) in humans. Radiolabeled PGE2 was injected intravenously into male subjects. 50% of the radioactivity was recovered in urine during the first 5 hours and less than 3% during the following 12 hours. The urine was acidified, and this extract was subjected to reversed-phase partition chromatography. Formation of the major metabolite (depicted stereochemically in the text) from PGE2 involved 4 steps of reactions: 1) dehydrogenation of the alcohol group in the side chain; 2) reduction of the trans double bond; 3) 2 steps of beta oxidation; and 4) delta oxidation.     

Synthesis of 2•,3•-Dideoxy-3•-<Emphasis Type="Italic">C</Emphasis>-hydroxymethylcytidine Phosphonomethyl Derivatives

Phosphonomethyl substituted 2?,3?-Dideoxy-3?-C-hydroxymethylcytidines have been synthesized and evaluated for their anti HIV-1 activities. The sugar moiety was synthesized starting from (S)-5-hydroxymethylfuran-2-(5H)-one using photocatalyzed addition of methanol. Reduction of the lactone, condensation with silylated 4-methoxy-2(1H)pyrimidinone, followed by phosphonomethylation and deprotection gave the title compounds. The compounds were tested for inhibition of HIV-1 activity but did not show any significant antiviral activity.     

Synthesis of C 2 Symmetric Potential Inhibitors of HIV-1 Protease From D-Mannitol

ABSTRACT

D-Mannitol was used as precursor for the synthesis of acyclic C ₂ symmetric potential HIV-1 protease inhibitors. The 1- and 6-hydroxy groups of D-mannitol were substituted by -NHBoc, -NHValZ, -SAr, -SOAr and -SO₂Ar and the 2-and 5-hydroxy groups were benzylated. In some products one of the central hydroxyl groups was either inverted or deoxygenated. Despite a close structural similarity to previously published inhibitors none of the products showed significant inhibitory activity against HIV-1 protease.

     

Synthesis of 2,6-Dideoxy-6-Thio Derivatives of KDO

ABSTRACT

Ammonium 2,3,6-trideoxy-2,6-epithio-D-manno-2-octenoate (8), ammonium 2,3,6-trideoxy-2,6-epithio-D-glycero-D-talo-octanoate (10a), ammonium 2,3,6-trideoxy-2,6-epithio-D-glycero-D-galacto-octanoate (10b) and ammonium 2,3,6-trideoxy-2,6-epithio-oxa-D-glycero-D-galacto-octanoate (13) have been synthesised as potential inhibitors of the enzyme CMP-KDO synthetase. The key step in the synthesis of 8 was the elimination of water from methyl 3,6-dideoxy-4,5:7,8-di-O-isopropylidene-6-thio-D-manno-2-octulosonate (4) using chlorodiphenylphosphine, imidazole and bromine to give the unsaturated methyl 2,3,6-trideoxy-2,6-epithio-4,5:7,8-di-O-isopropylidene-D-manno-2-octenoate (5). For the synthesis of 10a and 10b, zinc reduction of methyl 3,6-dideoxy-4,5:7,8-di-O-isopropylidene-6-S-(4-methoxybenzyl)-6-thio-2-O-(trichloro-tert-butoxycarbonyl)-D-manno-2-octenoate (2) gave an epimeric mixture of an α-hydroxyester 6 which was ring closed by in situ activation of the hydroxyl group using triphenylphosphine and tri-iodoimidazole followed by cleavage of the p-methoxybenzyl group to give 7a and 7b, which then were deprotected to give 10a and 10b.     

Thiol–ene coupling reaction of fatty acid monomers

The reactivities and reaction rates of the thiol–ene coupling reaction of 2‐ethyl‐(hydroxymethyl)‐1,3‐propanediol trimercapto acetate and 2‐ethyl‐(hydroxymethyl)‐1,3‐propanediol trimercapto propionate with two common unsaturated fatty acid methyl esters (methyl oleate and methyl linoleate) were evaluated. The reactions were monitored with real‐time IR and ¹H NMR, which both showed that the mercapto acetate was more reactive than the mercapto propionate. Both thiols were more prone to add to the monounsaturated methyl oleate than to methyl linoleate, which contained two unconjugated double bonds. According to bond energy calculations, the thiol hydrogen of mercapto acetate was somewhat more difficult to abstract than the hydrogen of mercapto propionate. Consequently, the formed S? C bond in the acetate case was stronger than in the propionate case, and so the equilibrium was more shifted toward the addition products. The real‐time IR measurements also showed that the cis unsaturation in methyl oleate isomerized much more quickly than that in methyl linoleate, and this also had an impact on the overall addition rate of the thiols because a trans unsaturation was more reactive than a cis unsaturation. The higher isomerization rates in the oleate systems, compared with those of the linoleate systems, was suggested to be due to a more restricted rotation along the C? C bond of the reacted unsaturation in linoleate. This study showed the importance of trans unsaturations in obtaining reasonable reaction rates in thiol–ene reactions with fatty acid derivatives. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 6346–6352, 2004     

Electron ionization mass spectrometry for sequence analysis of glycosphingolipid mixtures by fractional evaporation in the ion source. Mass spectrometric evidence for an eleven-sugar glycolipid

This paper describes the use of electron ionization mass spectrometry for structural characterization of a mixture of glycosphingolipids from a single human kidney and presents mass spectrometric evidence for the presence of an eleven-sugar glycolipid. A large amount of structural information is obtained from minor glycolipid constituents having long sugar chains by a fractional evaporation in the ion source, achieved by steadily increasing the ion-source temperature.