The Upjohn Co.

David G Martin

Ladislav J Hanka

Robert C Kelly

Paul A Aristoff

This invention concerns 2-acyl-4,5,8,8a-tetrahydro-4-oxycyclopropan[c]pyrrol(3,2-e) indole derivatives of Formula I': ##STR1## the compounds of Formula I' are useful as uv light absorber substances, as chemical intermediates and as prodrugs of known spirocyclopropylpyrroloindole CC-1065 analogs. Representative Formula I' compounds have been shown to possess useful ranges of antitumor activity in standard laboratory animal tests.

CC-1065 analogs

Process for the purification of L-(.alpha.S,5S)-.alpha.-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125). Also provided are AT-125 analogs prepared in the process.

Purification of AT-125

Process for the purification of L-(.alpha.s,5s)-.alpha.-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125). Also provided are AT-125 analogs prepared in the process.

Novel antibiotic CC-1065 producible in a fermentation under controlled conditions using the new microorganism Streptomyces zelensis, NRRL 11,183. This antibiotic is active against Gram-positive bacteria, for example, Staphylococcus aureus, Bacillus subtilis, Streptococcus pyogenes, Sarcina lutea, and Streptococcus faecalis. It is also active against Gram-negative bacteria, for example, Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Salmonella pullorum. Thus, antibiotic CC-1065 can be used in various environments to eradicate or control such bacteria.

Composition of matter and process

Novel antibiotic U-36,699 which has been identified as the .alpha.-methylene derivative of pentalenolactone. Antibiotic U-36,699 has the following structural formula ##STR1## This antibiotic is produced in a chemical process using pentalenolactone (also known as antibiotic P.A. 132), as the starting material. Antibiotic U-36,699 is active against Staphylococus aureua, Sarcina lutea, Mycobacterium phlei, Mycobacterium avium, Saccharomyces cerevisiae, and Penicillium oxalicum. Thus, antibiotic U-36,699 can be used in various environments to eradicate or control such fungi and bacteria. Further, antibiotic U-36,699 inhibits P 388 leukemia cells in laboratory mice. Thus, this antibiotic can be used to treat laboratory mice harboring P 388 leukemia cells.

Antibiotic pentalenolactone derivative

Antibiotic U-43,795, producible by culturing Streptomyces sviceus in an aqueous nutrient medium has the following structure ##EQU1## The absolute configuration of U-43,795 was determined to be .alpha.S, 4S, 5R .alpha.-amino-3-chloro-4-hydroxy-2-isoxazoline-5-acetic acid. It is an amphoteric compound and can exist in different ionic forms according to the pH of the environment. At low pH, U-43,795 exists in the acid-addition salt form, at a higher pH in a zwitterion form, and at still higher pH in a metal salt form. U-43,795 inhibits the growth of Bacillus subtilis and Sarcina lutea, and can be used to inhibit such microorganisms in various environments.

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Kalamazoo, MI, United States of America

David G Martin