cis-2-Amino-1-hydroxycyclobutane-1-acetic acid, a herbicidal antimetabolite produced by streptomyces rochei A 13018.

Abstract

Microorganisms represent a well-documented source of herbicidal compoundswith the potential to provide agricultural researchers with new structural classes for herbicide synthesis efforts1*. In the continuation of a screening programto discover novel natural product herbicides from microbial sources2), Streptomyces rochei A13018 was found to produce ds-2-amino-l-hydroxycyclobutane-lacetic acid (CBAA: 1), which causes L-cysteineor L-methionine-reversible chlorosis in Arabidopsis thaliana. CBAA is a constituent of the naturally occuring antibacterial dipeptide (l S,2£> l-hydroxy-2-[(5)-valylamino]cyclobutane-l-acetic acid (2)3), and has been reported synthetically by Baldwin et alf^. However,no previous reports cite the isolation of CBAAas the free amino acid or describe its herbicidal properties. This note briefly describes the producing organism, fermentation, isolation, structure identification, and biological activities of CBAA. Strain A13018 was isolated from a soil sample collected in Madera Canyon, Santa Rita Mountains, Arizona, U.S.A. The aerial mycelium bore chains of spores forming spirals (S), as described by

Bioactive cyclobutane-containing alkaloids

“…More recently, amino acids (2), (117), and (118) were isolated from A. herbert-smithii, B. alterna, B. decipiens, B. limae, B. mollis, and B. racemulosa [14]. The cis-2-amino-1-hydroxy-cyclobutaneacetic acid (119) was isolated from S. rochei and showed herbicidal activity [199].…”

“…Their structures are shown in Fig. 56 (185)(186)(187)(188) Antidepolarizing agents anatruxonium (199), truxillonium (200), pyrocyclonium (201), and cyclobutonium (202) have been synthesized and their biological activities reported [261][262][263]. In rabbits, cats, chicks, and guinea pigs, the four compounds possess high curarelike properties.…”

“…Their effective dose to block transmission from the sciatic nerve to the gastrocnemius muscle in cats is 100-150 lg/kg i.v. The low toxicity of (199) was evidenced by the fact that the dose required for heart arrest was at least three orders of magnitude higher than the one that produced muscular paralysis in animals under artificial respiration. Use of the four compounds in the clinic was recommended.…”

“…Use of the four compounds in the clinic was recommended. Structures of compounds (199) and (200) are shown in Fig. 57 and compounds (201) and (202) in Fig.…”

Natural Phytotoxins as Herbicides

“…Ciy-2-amino-l-hydroxycyclobutane-1-acetic acid (CBAA) produced by Streptomyces rochei (79) is a constituent of a naturally occurring antibiotic dipeptide (80). CBAA causes methionineand cysteine-reversible chlorosis in plants.…”