The Structure and Synthesis of Malformin A

Abstract

A structure (the disulfide form of cyclo-D-cysteinyl-L-valyl-D-cysteinyl-D-leucyl-L-isoleucyl), previously proposed for malformin A, was reexamined. On the basis of chemical degradations, a different structure (the disulfide form of cyclo-D-cysteinyl-D-cysteinyl-L-valyl-Dleucyl-L-isoleucyl) was established. Accordingly, a compound with this structure was synthesized and was found to be identical with malformin A. The synthetic product causes curvatures on corn roots; maximum effect was seen at a concentration of 0.1 Lg/ml, the optimal concentration for malformin A.Malformin, a metabolic product of Aspergillus niger, induces curvatures on bean plants and on corn roots. It was discovered (1-3) and isolated by Roy W. Curtis, who also demonstrated that malformin consists of a family of cyclic peptides. The best-studied member of this family, malformin A (4), is composed of two half-cystine residues, and one each of leucine, valine, and isoleucine, while other malformins contain alloisoleucine (5) or valine (6) instead of isoleucine. The configuration of the amino acid residues and their sequence was determined by Marumo and Curtis (5). Synthesis of a compound with the cyclic pentapeptide structure (Fig. 1, compound I) proposed for malformin A was reported by Isono and Curtis (7) in 1964; however, the synthetic preparation showed no malformin-like activity.Malformin was called to our attention by Prof. David Perlman of the University of Wisconsin, who pointed out that in addition to causing distortions on plants, malformins also have antibiotic activity (8) and inhibit mitosis as well (9); therefore, they are compounds of general biochemical interest. At the time when our engagement in research on malformin was under consideration, a series of papers (10-14) appeared from the laboratory of Alfons Sch6berl, describing the synthesis of compound I. The synthetic cyclopentapeptide could I I t D-Cys-Val-D-Cys-D-Leu-ile

d‐Cysteine desulfhydrase of Escherichia coli

“…The present work has demonstrated that the enzyme which catalyzes the a$-elimination reaction of D-cysteine, D-cysteine desulfhydrase, occurs in E. [32], contain Dcysteine as a component. Therefore, it might be possible that D-cysteine desulfhydrase takes part in the detoxification of catabolic degradation of D-cysteine-containing toxic compounds, which happen to invade or to be produced in bacterial cells.…”

Induction of Resistance to Dark Abscission by Malformin in White Light

“…Malformin, cyclo-D-cysteinyl-D-cysteinyl-L-valyl-L-leucyl-Lisoleucyl (2), is a potent plant growth regulatory produced by the fungus Aspergillus niger (4). The ability of malformin to stimulate plant growth in light was recently shown to involve phytochrome (8).…”

Total Synthesis of Malformin C, an Inhibitor of Bleomycin-Induced G2 Arrest

“…The less hindered amide bond between D-cysteine and L-valine was chosen for cyclization because the cyclization position between Dleucine and L-isoleucine has already been investigated in the stepwise synthesis of malformin A1 [7].…”