A process for preparing 4-deoxy-thiazolo[5,4-c]rifamycin SV derivatives of the following general formula ##STR1## wherein R represents hydrogen or a straight or branched alkyl chain containing from 1 to 10 carbon atoms, R.sub.1 is selected from hydrogen and acetyl. Compounds of formula I above, wherein R is a straight or branched alkyl chain containing from 1 to 10 carbon atoms, R.sub.1 is selected from hydrogen and acetyl. These compounds possess antimicrobial utility.

BACKGROUND OF THE INVENTION 
The compound of formula I above wherein R is hydrogen and R.sub.1 is acetyl 
is known as rifamycin P. It is described in U.S. Pat. No. 4,042,683 which 
also reports its preparation by fermentation of Nocardia Mediterranea 
strains ATCC 31064, 31065, 31066. 
SUMMARY OF THE INVENTION 
The present invention refers to a chemical process for preparing 
4-deoxythiazolo[5,4-c]rifamycin SV derivatives of the general formula 
##STR2## 
wherein R represents hydrogen or a straight or branched alkyl chain 
containing from 1 to about 10 carbon atoms and R.sub.1 is selected from 
hydrogen and acetyl. Representative members of the above mentioned alkyl 
chain are methyl, ethyl, propyl, isopropyl, butyl, sec.-butyl, isobutyl, 
tert.-butyl, pentyl, isopentyl, neopentyl, hexyl, 2-ethylbutyl, 
2-methylpentyl, 3-methylpentyl, 2,3-dimethylbutyl, heptyl, 2-ethylpentyl, 
3-ethylpentyl, 2-methylhexyl, 2,3-dimethylpentyl, 2,4-dimethylpentyl, 
octyl, 2-methylheptyl, 3-methylheptyl, 4-methylheptyl, 3-ethylhexyl, 
2,3,4-trimethylpentyl, 3,4-dimethylhexyl, 2-methyl-3-ethylpentyl, nonyl, 
2-methyloctyl, 3-methyl-4-ethylhexyl, 3,3,4-trimethylhexyl, 
3,4,5-trimethylhexyl, 4-methyloctyl, 4-ethylheptyl, decyl, 5-methylnonyl, 
3-methyl-2-ethylheptyl, 1-methylnonyl, 2,3,5-trimethylheptyl, 
3-methyl-4-ethylheptyl, 2,2,3,3-tetramethylhexyl, 4-propylheptyl, 
3,3-dimethyloctyl, 4-ethyloctyl and 2,4-dimethyl-3-ethylhexyl. 
The invention also refers to the compounds of formula I wherein R is a 
straight or branched alkyl group containing from 1 to about 10 carbon 
atoms and R.sub.1 is selected from hydrogen and acetyl. The compounds 
possess antimicrobial utility. 
A preferred group of compounds comprises those compounds of formula I 
wherein R is a straight or branched alkyl chain containing from 1 to about 
6 carbon atoms and R.sub.1 is selected from hydrogen and acetyl. 
A most preferred group of compounds comprises those compounds of formula I 
wherein R is a straight or branched alkyl chain containing from 1 to about 
6 carbon atoms and R.sub.1 is acetyl. 
The compound of formula I wherein R is hydrogen and R.sub.1 is acetyl 
corresponds to the natural product defined in U.S. Pat. No. 4,042,683 as 
rifamycin P. This microbiologically active metabolite was obtained 
together with other natural products by fermenting strains of Nocardia 
Mediterranea identified through the following ATRCC numbers: 31064, 31065 
and 31066. 
Accordingly, a further scope of the invention is a new and convenient route 
for preparing the known antibiotic substance rifamycin P. 
The process of the invention involves the condensation of rifamycin S (or 
the corresponding 25-desacetyl derivative) with a suitable thioaminoacid 
according to the following scheme: 
##STR3## 
In the actual practice, the process of the invention is carried out simply 
by dissolving a molar proportion of rifamycin S or its 25-desacetyl 
derivative in a suitable organic solvent, such as, for instance, a lower 
alkanol containing from 1 to 4 carbon atoms, a lower halogenated 
hydrocarbon containing from 1 to 2 carbon atoms, ethyl acetate, dioxane, 
tetrahydrofuran and analogs, and adding to this solution an amount of the 
selected thioaminoacid of formula III corresponding to from about 1 to 
about 2 molar equivalents over the starting rifamycin of formula II. An 
amount of a tertiary organic nitrogen containing base corresponding to 
about 2 molar proportions over the starting rifamycin of formula II can be 
added to the reaction mixture in order to favor the formation of the 
desired end compounds. 
Suitable amines which can be employed are trimethylamine, triethylamine, 
pyridine, pycoline, quinoline, isoquinoline and analogs. Though these 
amines impart to the solution an alkaline pH, it has been found that the 
reaction course is not affected by the pH of the medium, as good yields of 
compounds of formula I are obtained also by operating both under neutral 
or acidic conditions. The reaction mixture is then allowed to stand for 
from about 2 to about 10 hours at a temperature from between about room 
temperature and about 50.degree. C. until the investigation by thin layer 
chromatography shows the disappearance of rifamycin S, the presence of a 
new spot with a R.sub.f value of 0.8 and the spot due to rifamycin SV with 
Rf=0.05. The desired end compounds of formula II are finally recovered and 
purified by means of the usual chemical procedures. 
Such procedures comprise the evaporation to dryness of the reaction 
solution, purification of the residue by column chromatography and final 
recrystallization from suitable solvents. 
As stated above, the compounds of formula I wherein R represents a straight 
or branched alkyl group containing from 1 to 10 carbon atoms, which are 
4-deoxy-2'-alkyl-thiazolo[5,4-c]rifamycin SV derivatives and are an object 
of the present invention, possess antimicrobial utility. More exactly, 
they display a broad spectrum in vitro antibacterial activity against 
gram-positive and gram-negative microorganisms as well as mycobacteria as 
it can be seen from the hereinbelow reported table which shows the minimum 
inhibiting concentrations (MIC) of some representative members of the 
compounds of the invention. The MIC is expressed as .mu.g/ml. 
TABLE (MIC) 
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Compound of Example 
Strain 1 2 3 4 5 6 8 
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Staph. Aureus 
0.0004 
0.00078 
0.00078 
0.00078 
0.00078 
0.0012 
0.02 
Staph. Aureus Tour 
0.00078 
0.0031 
0.00156 
0.00156 
0.001 0.0031 
0.1 
Strept. haemolyticus 
0.012 0.0031 
0.0031 
0.012 0.001 0.012 
0.1 
Strept. faecalis 
0.0062 
0.0031 
0.00156 
0.012 0.0062 
0.012 
0.4 
Strept. pneumoniae 
0.0062 
0.0062 
0.00078 
0.012 0.0062 
0.012 
0.1 
Proteus vulgaris 
6.25 1.56 3.12 6.25 3.12 3.12 0.78 
Escherichia coli 
12.5 12.5 12.5 12.5 12.5 12.5 6.25 
Kleb. pneumoniae 
25.0 25.0 25.0 25.0 50.0 25 12.5 
Pseud. aeruginosa 
12.5 25.0 12.5 12.5 12.5 12.5 12.5 
Myc. Tub. H.sub.37 R.sub.v 
0.31 0.62 0.62 0.31 0.15 1.2 0.6 
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The 4-deoxy-2'-alkyl-thiazolo[5,4-c]rifamycin SV derivatives of the present 
invention are also effective against rifampicin resistant Staphylococcus 
aureus strains and possess an outstanding in vivo activity against 
experimental infection by Staphylococcus aureus when administered both per 
os and subcutaneously. This in vivo activity, expressed as an ED.sub.50, 
may vary from about 0.3 to about 1 mg/kg per os and from about 0.1 to 
about 0.4 mg/kg subcutaneoulsy.