Title: Verrucarins
Literature References: Macrocyclic tricothecane derivs which are secondary metabolites of the soil fungi Myrothecium verrucaria (Albertini et Schweinitz) Ditmar ex Fries; they are characterized by antibiotic, antifungal, and cytostatic activity. Verrucarins are triesters of the sesquiterpene alcohol verrucarol and closely related to the roridins, which are diesters of the same alcohol. Isoln of verrucarins A (major), B, C, D, E, F, G: E. Haerri et al., Helv. Chim. Acta 45, 840 (1962). Isoln of A: Symth, Kraskin, US 3087859 (1963 to Rohm & Haas); Vittimberga, J. Org. Chem. 28, 1786 (1963). Identity with muconomycin A: Vittimberga, Vittimberga, ibid. 30, 746 (1965). Structure of A: J. Gutzwiller, C. Tamm, Helv. Chim. Acta 48, 157 (1965). Stereochemistry: W. Zürcher et al., ibid. 840; A. T. McPhail, G. T. Sim, J. Chem. Soc. C 1966, 1394. Synthesis of A: W. C. Still, H. Ohmizu, J. Org. Chem. 46, 5242 (1981). Isoln of B: W. Loeffler et al., BE 627002 (1963 to Sandoz), C.A. 60, 10485b (1964). Structure of B: J. Gutzwiller, C. Tamm, Helv. Chim. Acta 48, 177 (1965). Toxicological studies of A and B: Guarino et al., Biotechnol. Bioeng. 10, 457 (1968); of A: Mortimer et al., Res. Vet. Sci. 12, 508 (1971). Biosynthetic studies of A and B: B. Müller, C. Tamm, Helv. Chim. Acta 58, 483 (1975); G. A. Cordell, Chem. Rev. 76, 425 (1976). Isoln of J (muconomycin B): Vittimberga, Vittimberga, loc. cit.; of H and J: B. Boehner et al., Helv. Chim. Acta 48, 1079 (1965). Structure of J: E. Fetz et al., ibid. 1669. Partial synthesis of tetrahydroverrucarin J and revised structure of J: W. Breitenstein, C. Tamm, ibid. 61, 1975 (1978). Isoln and structure of K: eidem, ibid. 60, 1522 (1977). Isoln of L: B. B. Jarvis et al., J. Antibiot. 34, 121 (1981). Total synthesis of verrucarol: R. H. Schlessinger, R. A. Nugent, J. Am. Chem. Soc. 104, 1116 (1982). Toxicity study: E. M. Rüsch, H. Stählin, Arzneim.-Forsch. 15, 893 (1965). Comprehensive review of the verrucarins and roridins: C. Tamm, Fortschr. Chem. Org. Naturst. 31, 64-117 (1974). For a description of the stereochemistry of the roridins see B. R. Jarvis et al., J. Nat. Prod. 45, 440 (1982).
Derivative Type: Verrucarin A
CAS Registry Number: 3148-09-2
Additional Names: Muconomycin A
Molecular Formula: C27H34O9
Molecular Weight: 502.55
Percent Composition: C 64.53%, H 6.82%, O 28.65%
Properties: Colorless rectangular plates from ether/acetone, mp >360° (dec). [a]D23 +206° (c = 1.012 in chloroform); uv max (ethanol): 260 nm (log e 4.25). LD50 in mice, rats, rabbits (mg/kg): 1.5, 0.87, 0.54 i.v. (Rüsch, Stählin).
Melting point: mp >360° (dec)
Optical Rotation: [a]D23 +206° (c = 1.012 in chloroform)
Absorption maximum: uv max (ethanol): 260 nm (log e 4.25)
Toxicity data: LD50 in mice, rats, rabbits (mg/kg): 1.5, 0.87, 0.54 i.v. (Rüsch, Stählin)
Derivative Type: Verrucarin B
CAS Registry Number: 2290-11-1
CAS Name: (2¢S,3¢R)-2¢-Deoxy-2¢,3¢-epoxyverrucarin A
Molecular Formula: C27H32O9
Molecular Weight: 500.54
Percent Composition: C 64.79%, H 6.44%, O 28.77%
Properties: Colorless needles from acetone/ether, decomp >330°. [a]D23 +147° (c = 1.066 in benzene). [a]D22 +101 ±1.5° (c = 1.416 in dioxane). uv max (methanol): 258.5 nm (log e 4.37).
Optical Rotation: [a]D23 +147° (c = 1.066 in benzene); [a]D22 +101 ±1.5° (c = 1.416 in dioxane)
Absorption maximum: uv max (methanol): 258.5 nm (log e 4.37)
Derivative Type: Verrucarin J
CAS Registry Number: 4643-58-7
CAS Name: (2¢E)-2¢,3¢-Didehydro-2¢-deoxyverrucarin A
Additional Names: muconomycin B
Molecular Formula: C27H32O8
Molecular Weight: 484.54
Percent Composition: C 66.93%, H 6.66%, O 26.42%
Properties: Crystals from ether, dec >235°. [a]D19 +54° (benzene). [a]D22 +20 ± 2° (c = 1.011 in chloroform). uv max: 261, 220.5 nm (e 22000, 21600).
Optical Rotation: [a]D19 +54° (benzene); [a]D22 +20 ± 2° (c = 1.011 in chloroform)
Absorption maximum: uv max: 261, 220.5 nm (e 22000, 21600)
Derivative Type: Verrucarin K
CAS Registry Number: 63739-93-5
CAS Name: 12,13-Deepoxy-12,13-didehydroverrucarin A
Molecular Formula: C27H34O8
Molecular Weight: 486.55
Percent Composition: C 66.65%, H 7.04%, O 26.31%
Properties: Crystals from methylene chloride/ether, dec >320°. [a]D23 +218 ±2° (c = 0.58 in chloroform). uv max (ethanol): 259 nm (log e 4.19).
Optical Rotation: [a]D23 +218 ±2° (c = 0.58 in chloroform)
Absorption maximum: uv max (ethanol): 259 nm (log e 4.19)
CAUTION: Verrucarins are extremely toxic; can cause severe local irritation and inflammation of the skin. |