The first direct synthesis of (+)-lysergic acid (2a) suitable for scale-up has been achieved by the following reaction sequence. Bromoketones 4d or 4g were allowed to react with amine 5 followed by deprotection, and the resulting diketone 6c was transformed into the unsaturated ketone (+/-)-7 by the LiBr/Et(3)N system. Resolution afforded (+)-7, which was further transformed by Schöllkopf's method into the mixture of esters 2e and 2f. Upon hydrolysis the latter mixture afforded (+)-2a. The peptide part of alpha-ergocryptine (1) was prepared according to the Sandoz method; the stereoefficiency, however, has been significantly improved by applying a new resolution method and recycling the undesired enantiomer. Coupling the peptide part with lysergic acid afforded 1. Having synthetic (+)-7 in hand, we can claim the total synthesis of all the alkaloids which were prepared earlier from (+)-7 that had been obtained through degradation of natural lysergic acid.
Griseochelin, C3,H;;QO" isolated from an asporogenous strain of Streptonryces griseus represents a novel carboxylic acid antibiotic. The metabolite, which is active against Grarnpositive bacteria, forms water-insoluble salts with mono-and divalent cations and binds alkaline-earth metal ions specifically in 2: 1 (X_M) stoichiometry.Detailed spectral (IR, MS and NMR) studies provide full characterization of its constitution featuring a carboxylic acid function, a substituted tetrahydropyran ring, an allylic OH group which are accomodated within a tetrahydroxylated-octamethyl-C" diene backbone.Griseochelin was isolated in the course of our investigations into the biochemistry of streptomycinnon-producing Amy-mutants derived from high-yielding streptomycin-producing strains of Strepto-
StrainThe griseochelin-producing strain, S. griseus ZIMET 43681, was taken from the strain collection of the Central Institute of Microbiology and Experimental Therapy, Jena. It represents a stable prototropic Amy-Str-mutant of the high-yielding, streptomycin-producing (Amy+ Str+) S. griseus HP strain". Derived from the parent strain via glycerol-limited chemostat cultivation, this mutant exhibits a number of modified biochemical properties. In particular, it excels in its capability to produce griseochelin under submerged cultivation in enhanced yields that may exceed those of the parent strain by a factor of 10 to 303).
FermentationLyophilized stock mycelia" were first propagated in agar slant cultures at 27°C for 8 days. The medium consisted of baker's yeast 1.5 %, maize starch 1 %, NaCI 0.5 %, peptone (Difco 0.1 %) and agar 2Y. and had a pH 7.0. Samples of the slant cultures were then used to inoculate the growth medium
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