An iridoid diester from valeriana officinalis var. sambucifolia hairy roots

A new iridoid diester (1R,2S,6S,9S)-5-acetyloxymethyl-9-methyl-3-oxabicyclo[4.3.0.]non-4-en-2-yl isovalerate), which we have named valdiate, was isolated from the hairy roots of Valeriana officinalis var. sambucifolia Mikan transformed with Agrobacterium rhizogenes R1601. It was characterized by its chemical and physical data. Together with valdiate, five valepotriates were isolated and identified by means of mass spectrometry and 1H and 13C NMR spectrometry. The analysis of the non-transformed plant roots belonging to the same species, indicated the absence of valdiate and the presence of four valepotriates only

Acid-catalysed backbone rearrangement of cholesta-6,8(14)-diene

Rearrangement of 5- and 5-cholesta-6,8(14)-dienes (13a and 13b, resp.) in the presence of anhydrous toluene-4-sulfonic acid in acetic acid leads to 5- and 5-12(13 14)-abeo-cholesta-8,13(17)-dienes (15a and 15b, resp.) via 5- and 5-cholesta-8,14-dienes (14a and 14b, resp.), respectively. Epimerization at C(20) of the spirosteradienes 15a and 15b occurs with increasing reaction time. Molecular-mechanics calculation of the relative stabilities of these compounds and of congeners thereof is in agreement with the observed reaction pathway

Synthesis of 1,2-dioxanes from an endoperoxide

1,4-Diphenylcyclopent-2-ene 1,4-endoperoxide (1) on catalysis with trimethylsilyl trifluoromethanesulfonate reacted with 1,4-diphenyl-1,3-cyclopentadiene in a diastereospecific manner to give cis,cis-3a,5a,8a,8b-tetrahydro-2,5a,7,8b-tetraphenyl-1H,6H-dicyclopenta[c,e]-1,2-dioxine (3), the structure of which was determined by X-ray, 2,5-Diphenylfuran, 1,1-diphenylethylene and styrene also reacted with 1 under the same conditions to yield the cis-fused analogues of 3 in high yield

New Cyclization Reaction at the Amino Terminus of Peptides and Proteins

Mild oxidation with periodate of the 1-amino-2-ol moiety of N-terminal seryl or threonyl peptides and proteins leads to a terminal aldehyde function O=CH-CO- which usually may be exploited for bioconjugate formation (e.g., via oximation with an O-alkyl hydroxylamine). We report that, when followed by a prolyl residue, the O=CH-CO- group can undergo a rapid cyclization and dehydration reaction through nucleophilic attack by the amide nitrogen of the third amino acid residue of the chain. We have characterized the resulting heterocycle, which is stable in aqueous acid, by mass spectrometry and NMR. Quantitative oximation can nevertheless be achieved in such cases by performing a one-pot oxidation-oximation without isolation of the intermediate aldehyde, as is demonstrated with cholera toxin B subunit

Involvement of <i>nodS</i> in <i>N</i>-Methylation and <i>nodU</i> in 6-<i>O</i>-Carbamoylation of <i>Rhizobium</i> sp. NGR234 Nod Factors

Although Rhizobium sp. NGR234 and Rhizobium fredii USDA257 share many traits, dysfunctional nodSU genes in the latter prohibit nodulation of Leucaena species. Accordingly, we used R. fredii transconjugants harboring the nodS and nodU genes of NGR234 to study their role in the structural modification of the lipo-oligosaccharide Nod factors. Differences between the Nod factors mainly concern the length of the oligomer (three to five glucosamine residues in USDA257 and five residues only in NGR234) and the presence of additional substituents in NGR234 (N-linked methyl, one or two carbamoyl groups on the non-reducing moiety, acetyl or sulfate groups on the fucose). R. fredii(nodS) transconjugants produce chitopentamer Nod factors with a N-linked methyl group on the glucosaminyl terminus. Introduction of nodU into USDA257 results in the formation of 6-O-carbamoylated factors. Co-transfer of nodSU directs N-methylation, mono-6-O-carbamoylation, and production of pentameric Nod factors. Mutation of nodU in NGR234 suppresses the formation of bis-carbamoylated species. Insertional mutagenesis of nodSU drastically decreases Nod factor production, but with the exception of sulfated factors (which are partially N-methylated and mono-carbamoylated), they are identical to those of the wild-type strain. Thus, Nod factor levels, their degree of oligomerization, and N-methylation are linked to the activity encoded by nodS

Synthesis, Structure, and Antimalarial Activity of Some Enantiomerically Pure, cis-fused cyclopenteno-1,2,4-trioxanes

Two pairs of enantiomerically pure cis-fused cyclopenteno-1,2,4-trioxanes (7, ent-7 and 8, ent-8) are prepared (Schemes 1-3). Their identities are established by dye-sensitized photo-oxygenation of ent-7 and 8, ent-8 to the allylichydroperxides, reduction to the corresponding alcohols, and conversion to the (1S)-camphanates (Scheme 4), the structures of which are determined by X-ray analysis. The dynamic properties of ent-7 are investigated by NMR spectroscopy and PM3 calculations. Evidence for an easily accessible twist-boat conformation is obtained. The in vitro and in vivo antimalarial activities of 7, ent-7,8, and ent-8 as well as those of the racemic mixtures are evaluated against Plasmodium falciparum, P. berghei, and P. yoelii. No correlation is observed between configuration and activity. Racemates and pure enantiomers have commensurate activities. The mode of action on the intraerythrocytic parasite is rationalized in terms of close docking by the twist-boat conformer of the trioxane on the surface of a molecule of heme, single-electron transfer to the O--O d* orbital, and scission to the acetal radical which then irreversibly isomerizes to a C-centered radical, the ultimate lethal agent (Scheme 5)