Determination of the absolute stereochemistry of the epoxide of Aoe (2-amino-8-oxo-9,10-epoxydecanoic acid) in Cyl-1 and Cyl-2 by CD spectra.

Abstract

Cyl-1 (I)1' and Cyl-2 (2)2~4) are phytotoxic cyclotetrapeptides isolated from a cultured broth of the phytopathogenic fungus, Cylindrocladium scoparium. They have the unique amino acid, Aoe (2-amino-8-oxo-9,10epoxy-decanoic acid) as a component. The configurations at the a-position of each four amino acids of Cyl-1 and Cyl-2 have been determined by physicochemical data or enzymatic reactions,1A) but the stereochemistry of the epoxide of Aoe remained uncertain. In this paper, we describe the determination of its stereochemistry by CDspectra. After the isolation of Cyl-2,2) several tetrapeptides

Histone Deacetylase: A Target for Antiproliferative and Antiprotozoal Agents

“…The fungus Cylindrocladium scoparium produced the prolyl-substituted Cyl-1 (40) as well as its pipecolyl-variant Cyl-2 (41); both were potent plant growth regulators [71][72][73]. The absolute stereochemistry of the Aoe moiety in Cyl-2 was determined using CD spectroscopy [74]. polar glycine variant of HC-toxin, cyclopeptide 37 (approximately 3% as active as HC-toxin).…”

Structure and Chemistry of Apicidins, a Class of Novel Cyclic Tetrapeptides without a Terminal α-Keto Epoxide as Inhibitors of Histone Deacetylase with Potent Antiprotozoal Activities

“…A small group of natural fungal cyclic tetrapeptides has been reported as antiproliferative or phytotoxic agents. These include HC-Toxin I ( 2 ), chlamydocin ( 3a ) 7 and analogue 3b , Cyl-1 ( 4a ) and Cyl-2 ( 4b ), WF-3161 ( 5 ), and trapoxins A ( 6a ) and B ( 6b ) . Like apicidin, these peptides contain a β-turn amino acid (Pro or Pip), and at least one of the amino acids has a d configuration, but unlike apicidin, all but 3b contain a (2 S ,9 S )-2-amino-8-oxo-9,10-epoxydecanoic acid (Aoe) residue with a highly electrophilic terminal α-keto epoxide.…”

Structure, Histone Deacetylase, and Antiprotozoal Activities of Apicidins B and C, Congeners of Apicidin with Proline and Valine Substitutions

“…In summary, we have discovered two novel cyclic tetrapeptides that show a variety of potent antiprotozoal activities by reversibly inhibiting HDAC. These are the new members of a unique family of cyclic tetrapeptides that do not require the electrophilic α-epoxyketone moiety of HC-toxin, trapoxin A, chlamydocin, cyl 1, and WF3161 to be active against HDAC and the malaria parasite. Further studies on the apicidins may lead to better antimalarial and antiprotozoal agents.…”