Structures of cytochalasins C and D

Abstract

The structures of cytochalasins C and D, metabolites of Metarrhizium anisopliae, have been determined.THE cytochalasins 1 are a new class of mould metabolite which produce unique effects on mammalian cells.2Cytochalasins A and By produced by Helminthosporium dematioideum, have been shown 1,3 to have structures (Ia) and (Ib) respectively (cytochalasin B is identical with phomin, a metabolite of a Phoma sp?), and the isolation of cytochalasins C and D from Metarr?zizium anisopZiae has been briefly reported.1 t We report here experiments which lead us to propose structures (IIa) and (111) for cytochalasins C and D respectively. The compounds are produced in rather low yield and are difficult to separate. In particular, it is difficult to obtain cytochalasin D, which is the minor product, free from cytochalasin C; for this reason, most of the degradative experiments have been carried out with cytochalasin C.Cytochalasins C and D are isomers C,H3,N0,. The nature of the isomerism and of a large part of the molecules is revealed most clearly by consideration of the properties of the isomeric carboxylic acids, C,H,,NO,, obtained by alkaline hydrolysis of the mould metabolites. The n.m.r. spectrum (Table ) of the product (IV) from cytochalasin C shows signals due to a phenyl ring, a tram-disubstituted double bond, a secondary hydroxygroup, two allylic methyl groups, a secondary methyl t Note added in proof: It is clear from its published i.r. spectrum that the recently isolated antibiotic zygosporin (S.

Identification and engineering of the cytochalasin gene cluster from Aspergillus clavatus NRRL 1

“…Cytochalasin C and D have been isolated from the entomopathogenic fungus M. anisopliae (Aldridge et al, 1967a; Aldridge and Turner, 1969). Like cytochalasin E and K, both cytochalasin C and D are derived from octaketide chain and contain a benzyl group originated from phenylalanine but lack the vinyl carbonate moeity (Figure 1).…”

Proxiphomin und Protophomin, zwei neue Cytochalasane

“…Die aus den Spektraldaten abgeleitete Struktur von 4 konnte zusatzlich durch einen ozonolytischen Abbau und Verknupfung der dabei erhaltenen Bruchstucke mit Phomin (5) und Cytochalasin D ( ( 7 S , 16S, 18 H, 21 R ) -21-Acetoxy-7,18-diliydroxy-16,18-dimcthyl-10-phenyl-jll]cytochalasa-6 (12), 13t, 19t-trien-l,l7-dion) [5] bewiesen werden. Es ist uns nun gelungen, aus Kulturen der genannten Phoma Species zwei weitere, in geringer Menge gebildete Metabolite zu isolieren, die das gleiche carbocyclische Grundgeriist wie Desoxaphomin (4) besitzen, aber weniger Sauerstoff als dieses enthalten.…”

Synthesis of 1233A analogs and their inhibitory activity against hydroxymethylglutaryl coenzyme A synthase.

“…The coupling constant,.7 (3,4) in the /Mactone (9b) was 4.0Hz, which is indicative for the trans geometry10). In contrast, /(3,4) in 9a was 6.5 Hz, indicative of cis geometry.…”