Isolation of (4R)-4-[(E)-2-butenyl]-4-methyl-L-threonine, the characteristic structural element of cyclosporins, from a blocked mutant of Tolypocladium inflatum.
By mutagenic treatment of a strain of Tolypocladium inflatum, a cyclosporin non-producing mutant was obtained which accumulated the characteristic building unit of cyclosporins, (4R)-4-[(E)-2-butenyl]-4-methyl-L-threonine (abbreviation Bmt; systematic name: (2S,3R,4R,6E)-2-amino-3-hydroxy-4-methyl-6-octenoic acid) in free form. The isolation from a culture filtrate was performed by extraction, chromatographic separation and final crystallization from methanol - water. The structure and stereochemistry of this amino acid was determined by chemical transformation and correlation to dihydro-MeBmt, with known chirality [(2S,3R,4R)-3-hydroxy-4-methyl-2-methylamino-octanoic acid], obtained by hydrolysis of dihydrocyclosporin A.
Sanglier
J J
JJ
Preclinical Research, Biotechnology, Sandoz Ltd., Basel, Switzerland.
Traber
R
R
Buck
R H
RH
Hofmann
H
H
Kobel
H
H
D055598:Chemical Phenomena; D002621:Chemistry; D003524:Cyclosporins / Q000096:biosynthesis*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D003904:Mitosporic Fungi / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D015394:Molecular Structure; D009154:Mutation; D013055:Spectrophotometry, Infrared; D013912:Threonine / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000302:isolation & purification; D014466:Ultraviolet Rays
D003524:Cyclosporins; D013912:Threonine; C065222:2-butenyl-4-methylthreonine