Title: Methylenomycins
Literature References: Members of a family of cyclopentenoid antibiotics related structurally to sarkomycins, q.v., and having in vitro activity vs gram-positive and gram-negative organisms. Isoln from Streptomyces violaceoruber, physical, chemical, biological properties: M. Arai et al., JP Kokai 73 19796 (1973 to Sankyo), C.A. 78, 157861 (1973); T. Haneishi et al., J. Antibiot. 27, 386 (1974). Structures of methylenomycins A and B: eidem, ibid. 393. Crystal and molecular structure of (±)-A: B. H. Toder, A. B. Smith, J. Cryst. Mol. Struct. 8, 1 (1979). Stereospecific total synthesis of (±)-A: R. M. Scarborough et al., J. Am. Chem. Soc. 99, 7085 (1977); eidem, ibid. 102, 3904 (1980); and absolute configuration: K. Sakai et al., Tetrahedron Lett. 1979, 2365. Stereospecific total synthesis and absolute configuration of (+)-A: J. Jernow et al., J. Org. Chem. 44, 4210 (1979). Revised structure and total synthesis of B: eidem, ibid. 4212. Concise synthesis of B: M. Mikolajczyk, R. Zurawinski, Synlett 8, 575 (1991). Prepn of analogs of A and structure-activity correlations: T. Haneishi et al., J. Antibiot. 27, 400 (1974). Toxicity: eidem, ibid. 386. Methylenomycin A is the first example of an antibiotic in which all information required for synthesis is carried by a plasmid, SCP1: L. F. Wright, D. A. Hopwood, J. Gen. Microbiol. 95, 96 (1976). Review of biosynthesis: U. Hornemann, D. A. Hopwood, Antibiotics vol. IV, J. W. Corcoran, Ed. (Springer-Verlag, New York, 1981) pp 123-131. General review: A. Terehara et al., Heterocycles 13, 353-371 (1979).
Derivative Type: Methylenomycin A
CAS Registry Number: 52775-76-5
CAS Name: [1S-(1a,2a,5a)]-1,5-Dimethyl-3-methylene-4-oxo-6-oxabicyclo[3.1.0]hexane-2-carboxylic acid
Molecular Formula: C9H10O4
Molecular Weight: 182.17
Percent Composition: C 59.34%, H 5.53%, O 35.13%
Properties: Colorless crystals from chloroform/carbon tetrachloride, mp 115° (dec). mp of the (±)-form: 88.5-89°; after subl (70-75°, 0.025 mm Hg), 107.5-108°. [a]D20 +42.3° (c = 1 in chloroform). uv max (methanol): 224 nm (e 6300). Sol in benzene, chloroform, ethyl acetate, acetone, methanol, water. Slightly sol in n-hexane, CCl4. pKa¢ 3.65. LD50 in mice (mg/kg): 1500 orally, 75 i.p. (Haneishi).
Melting point: mp 115° (dec); mp of the (±)-form: 88.5-89°
pKa: pKa¢ 3.65
Optical Rotation: [a]D20 +42.3° (c = 1 in chloroform)
Absorption maximum: uv max (methanol): 224 nm (e 6300)
Toxicity data: LD50 in mice (mg/kg): 1500 orally, 75 i.p. (Haneishi)
Derivative Type: Methylenomycin B
CAS Registry Number: 52775-77-6
CAS Name: 2,3-Dimethyl-5-methylene-2-cyclopenten-1-one
Molecular Formula: C8H10O
Molecular Weight: 122.16
Percent Composition: C 78.66%, H 8.25%, O 13.10%
Properties: Neutral colorless oil. uv max (methanol): 240 nm (e 7650). Sol in ether, benzene, chloroform, ethyl acetate, acetone, alcohols. Slightly sol in n-hexane, petr ether. LD50 in mice (mg/kg): 260 orally, 245 i.p. (Haneishi).
Absorption maximum: uv max (methanol): 240 nm (e 7650)
Toxicity data: LD50 in mice (mg/kg): 260 orally, 245 i.p. (Haneishi)

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