8772. Distamycin A

Nomenclature

CAS number: 636-47-5
N-[5-[[(3-Amino-3-iminopropyl)amino]carbonyl]-1-methyl-1H-pyrrol-3-yl]-4-[[[4-(formylamino)-1-methyl-1H-pyrrol-2-yl]carbonyl]amino]-1-methyl-1H-pyrrole-2-carboxamide; β-[1-methyl-4-[1-methyl-4-(1-methyl-4-formylaminopyrrole-2-carboxamido)pyrrole-2-carboxamido]pyrrole-2-carboxamido]propionamidine; stallimycin; F.I. 6426.
C22H27N9O4; mol wt 481.51.
C 54.88%, H 5.65%, N 26.18%, O 13.29%.

Description and references

Antiviral antibiotic obtained from Streptomyces distallicus. Binds to the minor groove of DNA, preferentially to adenine-thymine rich sequences; inhibits DNA-dependent RNA synthesis. Isoln: F. Arcamone et al., DE 1039198 (1958 to Farmaceutici Italia), C.A. 55, 2012f (1961). Structure and synthesis: idem et al., Nature 203, 1064 (1964); eidem, Gazz. Chim. Ital. 97, 1097, 1110 (1967). Total synthesis: M. Bialer et al., Tetrahedron 1978, 2389; L. Grehn, U. Ragnarsson, J. Org. Chem. 46, 3492 (1981). Toxicity and antitumor activity: A. DiMarco et al., Cancer Chemother. Rep. 18, 15 (1962). Review: F. E. Hahn in Antibiotics vol. 3, J. W. Corcoran, F. E. Hahn, Eds. (Springer-Verlag, New York, 1975) pp 79-100. Review of mechanism of action: H. Grunicke et al., Rev. Physiol. Biochem. Pharmacol. 75, 69-96 (1976). Review of use for targeted delivery of antitumor agents: P. G. Baraldi et al., Bioorg. Med. Chem. 15, 17-35 (2007).

Chemical structure

Derivative

Hydrochloride.

Nomenclature

CAS number: 6576-51-8
Herperal.
C22H27N9O4.HCl; mol wt 517.97.
C 51.01%, H 5.45%, N 24.34%, O 12.36%, Cl 6.84%.

Properties

White to yellow crystals from dil HCl, mp 184-187° (Arcamone, 1967). Also reported as 189-193° from ethanol-ethyl acetate (Bialer). Hygroscopic. Protect from light and oxygen. uv max (96% ethanol): 237, 303 nm (ε 30000, 37000). Sol in water; forms clear yellow to green solution at 20 mg/ml in ethanol. LD50 in mice (mg/kg): 75 i.v.; 500 i.p. (DiMarco).

Use

Biochemical tool to inhibit RNA synthesis.