Processes for preparing A54145 compounds
AssigneeEli Lilly and Company
InventorLaVerne D. Boeck
Life of this patent
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Abstract
Improved processes for preparing A54145 components and cyclic peptide derivatives (A54145 compounds) comprising: (1) feeding alkanoic or alkenoic acids or alcohols, or esters or salts thereof, (2) feeding glucose at a rate from about 6-9 g/L/day, or (3) feeding enzymatic soy digest at a rate from about 2-4 g/L/day to an A54145-producing culture during its fermentation and recovering the A54145 compound, are provided.
Claims13
A process for preparing an A54145 component of the formula:
- ##STR5## wherein Z is a group of formula ##STR6## R is selected from n-decanoyl, 8-methyldecanoyl and 8-methylnonanoyl;
- X is Ile or Val;
- and
- Y is Glu or 3-MG;
- provided that:
- (1) when X=Val and Y=3-MG, R must be 8-methyldecanoyl;
- and (2) when X=Val and Y=Glu, R must be 8-methylnonanoyl;
- which comprises adding a C.sub.4 -C.sub.18 alkyl or alkenyl alcohol, a C.sub.4 -C.sub.18 alkanoic or alkenoic acid, an ester of a C.sub.4 -C.sub.18 alkanoic or alkenoic acid, or a salt of a C.sub.4 -C.sub.18 alkanoic or alkenoic acid, to an A54145-producing culture of Streptomyces fradiae, strains NRRL 18158, NRRL 18159, or NRRL 18160, or an A54145-producing mutant thereof, starting from about 20 hours to about 26 hours after initiating the production stage, and continuing throughout the fermentation until a recoverable amount of A54145 component is produced.
A process for preparing an A54145 cyclic peptide derivative of the formula:
- ##STR7## wherein Z.sup.a is a group of formula ##STR8## R.sup.a is C.sub.6 -C.sub.10 alkanoyl;
- X is Ile or Val;
- and
- Y is Glu or 3-MG;
- provided that:
- (1) when X=Ile and Y=Glue or 3-MG, R.sup.a cannot be 8-methyldecanoyl, 8-methylnonanoyl, or n-decanoyl;
- (2) when X=Val and Y=3-MG, R.sup.a cannot be 8-methyldecanoyl;
- and
- (3) when X=Val and Y=Glu, R.sup.a cannot be 8-methylnonanoyl;
- which comprises adding a C.sub.6 -C.sub.10 alkyl or alkenyl alcohol, a C.sub.6 -C.sub.10 alkanoic or alkenoic acid, an ester of a C.sub.6 -C.sub.10 alkanoic or alkenoic acid, or a salt of a C.sub.6 -C.sub.10 alkanoic or alkenoic acid, to an A54145-producing culture of Streptomyces fradiae, strains NRRL 18158, NRRL 18159, or NRRL 18160, or an A54145-producing mutant thereof, starting from about 20 hours to about 26 hours after initiating the production stage, and continuing throughout the fermentation until a recoverable amount of the A54145 derivative is produced.
A process for preparing an A54145 compound of the formula:
- ##STR9## wherein Z.sup.b is a group of formula ##STR10## R.sup.b is C.sub.6 -C.sub.10 alkanoyl;
- X is Ile or Val;
- and
- Y is a Glue or 3-MG;
- which comprises feeding glucose at a rate from about 6 to about 9 grams/liter/day to an A54145-producing culture of Streptomyces fradiae, strains NRRL 18158, NRRL 18159, or NRRL 18160, or an A54145-producing mutant thereof, starting from about 18 hours to about 24 hours after initiating the production stage and continuing throughout its fermentation until a recoverable amount of an A54145 compound is produced.
A process for preparing an A54145 compound of the formula:
- ##STR11## wherein Z.sup.b is a group of formula ##STR12## R.sup.b is C.sub.6 -C.sub.10 alkanoyl;
- X is Ile or Val;
- and
- Y is Glu or 3-MG;
- which comprises feeding an enzymatic soy digest at a rate from about 2 to about 4 grams/liter/day to an A54145-producing culture of Streptomyces fradiae, strains NRRL 18158, NRRL 18159, or NRRL 18160, or an A54145-producing mutant thereof, starting from about 100 hours to about 120 hours after initiating the production stage and continuing throughout its fermentation until a recoverable amount of an A54145 compound is produced.
Dependencies are inferred from the claim text.