Title: Grayanotoxins
Literature References: Toxic diterpenoids present in leaves of the various species of Rhododendron, Kalmia, and Leucothoe, Ericaceae; also found in honey from rhododendron flowers. Eighteen grayanotoxins have been isolated, the first three being the most important. Isoln of grayanotoxins I, II, III: Kakisawa et al., Tetrahedron 21, 3091 (1965); of IV and V: Okuno et al., ibid. 26, 4765 (1970); of V, VI, and VII: Hikino et al., Chem. Pharm. Bull. 18, 2357 (1970); of VIII, IX, X, and XI: Hikino et al., ibid. 19, 1289 (1971); of XII and XIII: Hikino et al., ibid. 20, 422 (1972). Approaches to synthesis of the grayanotoxin skeleton: T. Shiozaki et al., Tetrahedron Lett. 1972, 657; T. Kametani et al., Chem. Pharm. Bull. 27, 152 (1979); eidem, Tetrahedron Lett. 22, 2379 (1981); eidem, Tetrahedron 37, 3813 (1981). Toxicity study: H. Hikino et al., Toxicol. Appl. Pharmacol. 35, 303 (1976).
Derivative Type: Grayanotoxin I
CAS Registry Number: 4720-09-6
CAS Name: (3b,6b,14R)-Grayanotoxane-3,5,6,10,14,16-hexol 14-acetate
Additional Names: G-I; acetylandromedol; andromedotoxin; rhodotoxin; asebotoxin
Molecular Formula: C22H36O7
Molecular Weight: 412.52
Percent Composition: C 64.05%, H 8.80%, O 27.15%
Literature References: From Leucothoe grayana Max., Ericaceae: Miyajimi, Takei, J. Agric. Chem. Soc. Jpn. 10, 1093 (1934); from Rhododendron maximum L., Ericaceae: Wood et al., J. Am. Chem. Soc. 76, 5689 (1954). Identity with acetylandromedol, andromedotoxin, rhodotoxin: Tallent et al., ibid. 79, 4548 (1957). Stereochemistry: Iwasa, Nakamura, Tetrahedron Lett. 1969, 3973; Narayanan et al., ibid. 1970, 3943; Hikino et al., Chem. Pharm. Bull. 18, 1071 (1970). Approach to synthesis: Okuno, Matsumoto, Tetrahedron Lett. 1969, 4077. Has hypotensive action: Moran et al., J. Pharmacol. Exp. Ther. 110, 415 (1954).
Properties: Crystals from ethyl acetate, mp 258-260 to 267-270°, depending on rate of heating. [a]D25 -8.8° (c = 2.3 in ethanol). Sol in hot water, alcohol, acetic acid, hot chloroform; very slightly sol in benzene, ether, petr ether. LD50 i.p. in mice: 1.31 mg/kg (Hikino, 1976).
Melting point: mp 258-260 to 267-270°
Optical Rotation: [a]D25 -8.8° (c = 2.3 in ethanol)
Toxicity data: LD50 i.p. in mice: 1.31 mg/kg (Hikino, 1976)
Derivative Type: Grayanotoxin II
CAS Registry Number: 4678-44-8
CAS Name: (3b,6b,14R)-Grayanotox-10(20)-ene-3,5,6,14,16-pentol
Additional Names: G-II; deacetylanhydroandromedotoxin
Molecular Formula: C20H32O5
Molecular Weight: 352.47
Percent Composition: C 68.15%, H 9.15%, O 22.70%
Literature References: From L. grayana Max., Ericaceae: Miyajimi, Takei, loc. cit. Identity with deacetylanhydromedotoxin: Meguri, Yakugaku Zasshi 79, 1060 (1959); C.A. 54, 5599g (1960). Stereochemistry: Iwasa, Nakamura, loc. cit.; Kumazawa, Iriye, Tetrahedron Lett. 1970, 927; Yasue et al., Chem. Pharm. Bull. 18, 2586 (1970). Synthesis: S. Gasa et al., Tetrahedron Lett. 1976, 553.
Properties: Columnar crystals, mp 199-200°. [a]D28 -41.88°. LD50 i.p. in mice: 26.1 mg/kg (Hikino, 1976).
Melting point: mp 199-200°
Optical Rotation: [a]D28 -41.88°
Toxicity data: LD50 i.p. in mice: 26.1 mg/kg (Hikino, 1976)
Derivative Type: Grayanotoxin III
CAS Registry Number: 4678-45-9
CAS Name: (3b,6b,14R)-Grayanotoxane-3,5,6,10,14,16-hexol
Additional Names: G-III; deacetylandromedotoxin
Molecular Formula: C20H34O6
Molecular Weight: 370.48
Percent Composition: C 64.84%, H 9.25%, O 25.91%
Literature References: From L. grayana Max., Ericaceae: Miyajimi, Takei, J. Agric. Chem. Soc. Jpn. 12, 947 (1936), C.A. 30, 67479 (1936). Stereochemistry: Hikino et al., Chem. Pharm. Bull. 18, 1071 (1970).
Properties: LD50 i.p. in mice: 0.84 mg/kg (Hikino, 1976).
Toxicity data: LD50 i.p. in mice: 0.84 mg/kg (Hikino, 1976)
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