Synthesis and evaluation of microtubule assembly inhibition and cytotoxicity of prenylated derivatives of cyclo-l-Trp-l-Pro

The synthesis of three isoprenylated derivatives of cyclo-L-Trp-L-Pro is described. These substances have been evaluated for cytotoxic activity in rat normal fibroblast 3Y1 cells and have also been evaluated in vitro for the inhibition of microtubule assembly.

Reverse versus Normal Prenyl Transferases in Paraherquamide Biosynthesis Exhibit Distinct Facial Selectivities

Both a face-selective and a non-face-selective mode of formation of quaternary centers of isoprene-derived structural moieties of the natural alkaloid paraherquamide A (1) have been discovered by feeding experiments on Penicillium fellutanum with [U-13 C6 ]-glucose and [13 C2 ]-acetate. The labeling patterns suggest that the methyl groups (C22, C23) are introduced in a non-face-selective manner by a reverse prenyl transferase. The C5 unit comprising the dioxepin moiety retains stereochemical integrity indicative of a single, face-selective addition of the phenolic group to the dimethylallyl group.

ChemInform Abstract: Studies on the Biosynthesis of Paraherquamide. Construction of the Amino Acid Framework.

Abstract It has been previously established in this laboratory that the β-methyl-β-hydroxyproline moiety of the potent anthelmintic agent paraherquamide A, is biosynthetically derived from l -isoleucine. The downstream events from l -Ile to paraherquamide A have now been investigated. The synthesis of [1- 13 C]-labeled l -β-methylproline is described by means of a Hoffman–Loeffler–Freytag reaction sequence from [1- 13 C]- l -Ile. This amino acid is shown to be a direct biosynthetic precursor to paraherquamide A by feeding and incorporation experiments in growing cultures of Penicillium fellutanum . Three tryptophan-containing dipeptides of l -β-methylproline have been constructed: [ 13 C 2 …

Reverse und „normale”︁ Prenyltransferasen haben unterschiedliche Seitenselektivitäten bei der Biosynthese von Paraherquamid

Sowohl eine seitenspezifische als auch eine seitenunspezifische Bildung quartarer C-Zentren aus von Isopren abgeleiteten Strukturelementen im Alkaloid Paraherquamid A 1 wurden durch [U-13C6]Glucose- und [13C2]Acetat-Futterungsexperimente mit Penicilliumfellutanum entdeckt. Aus dem Markierungsmuster last sich ableiten, das die Methylgruppen (C22, C23) seitenunspezifisch durch eine Reverse Prenyltransferase eingefuhrt werden. In der C5-Einheit, die den Dioxepinrest umfast, bleibt die relative Konfiguration erhalten, was fur eine einzige, seitenspezifische Addition einer Phenoleinheit an die Dimethylallylgruppe spricht.

Studies on the biosynthesis of paraherquamide. Construction of the amino acid framework

Abstract It has been previously established in this laboratory that the β-methyl-β-hydroxyproline moiety of the potent anthelmintic agent paraherquamide A, is biosynthetically derived from l -isoleucine. The downstream events from l -Ile to paraherquamide A have now been investigated. The synthesis of [1- 13 C]-labeled l -β-methylproline is described by means of a Hoffman–Loeffler–Freytag reaction sequence from [1- 13 C]- l -Ile. This amino acid is shown to be a direct biosynthetic precursor to paraherquamide A by feeding and incorporation experiments in growing cultures of Penicillium fellutanum . Three tryptophan-containing dipeptides of l -β-methylproline have been constructed: [ 13 C 2 …

Studies on the Biosynthesis of Paraherquamide: Synthesis and Incorporation of a Hexacyclic Indole Derivative as an Advanced Metabolite