Bohemic acid

Synthesis and fractions

Bohemic acid is produced through fermentation by an actinobacteria species in the genus Actinosporangium (Actinoplanaceae) in the order Actinomycetales. Specifically, strain C36145 (ATCC 31127) produces bohemic acid. The acid can be extracted from the fermentation broth with methyl isobutyl ketone under neutral or slightly basic pH conditions, and the fats and oils are removed by washing with petroleum ether.

Chromatographical separation, in addition to the antibiotics pyrromycin and cinerubin A and B, reveals several individual components of bohemic acid, including alcindoromycin, bohemamine, collinemycin, marcellomycin, mimimycin, musettamycin, rudolphomycin and schaunardimycin. Their names originate from the characters Alcindoro, Colline, Marcello, Mimì, Musetta, Rodolfo (Rudolph) and Schaunard of the Puccini opera La Bohème, and the acid itself and the bohemamine component carry the name of the opera. The suffix -mycin is conventionally added to indicate antibiotics derived from actinobacteria or fungi.

Properties

The individual components of bohemic acid are orange-red solids, the color originating from an optical absorption band centered at about 490 nm. Marcellomycin and mimimycin, and collinemycin and musettamycin are stereoisomers, that is they have the same chemical compositions; however, one C-H and one COOCH3 group exchange places. Those two groups are attached to the same carbon atom of one carbon ring, they are marked by the blue star in their structure in the table (C-H group is not shown). The original studies on the individual components of bohemic acid have tested them all for antitumor activity in mice, upon intraperitoneal injection.

The median lethal dose (LD50) of marcellomycin depends strongly on the animal and varies from a few mg/kg of body weight (dogs) to 20 mg/kg (Suiss-Webster mice, intravenal injection), the major site of toxicity being the gastrointestinal tract. Bohemamine has several structural varieties and derivatives, such as bohemamine B (C14H20N2O3), bohemamine C (C14H21N2O3), and 5-chlorobohemamine C (C14H20ClN2O3). None of them showed antibiotic, antifungal or antitumor activity.

The bottom fragment of rudolphomycin is a cyclic (sugar) compound with a chemical formula C6H8NO3 and a proposed trivial name rednose.

References

References

1. (1980). "Antitumor Agents From Bohemic Acid Complex, III. The Isolation of Marcellomycin, Musettamycin, Rudolphomycin, Mimimycin, Collinemycin, Alcindoromycin, and Bohemamine". Journal of Natural Products.
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6. {{OED. mycin
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8. (1978). "Comparative Ultrastructural Studies of Nucleoli of Tumor Cells Treated with Adriamycin and the Newer Anthracyclines, Carminomycin and Marcellomycin". Cancer Research.
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10. (1983). "A phase I trial of marcellomycin with a weekly dose schedule". European Journal of Cancer and Clinical Oncology.
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12. (2006). "Bohemamines from a Marine-Derived Streptomyces addafgaffewtsp.". Journal of Natural Products.
13. (1980). "Isolation and structure of bohemamine (1aβ,2α,6aβ,6bβ)-3-methyl-N-(1a,6,6a,6b-tetrahydro-2,6a-dimethyl-6-oxo-2H-oxireno[a]pyrrolizin-4-yl)-2-butenamide". The Journal of Organic Chemistry.
14. (1979). "Antitumor agents from the bohemic acid complex. 4. Structures of rudolphomycin, mimimycin, collinemycin, and alcindromycin". J. Am. Chem. Soc..