CA1089453A

CA1089453A - Rifamycin compounds

Info

Publication number: CA1089453A
Application number: CA304,380A
Authority: CA
Inventors: Leonardo Marsili; Vittorio Rossetti; Carmine Pasqualucci
Original assignee: ARCHIFAR LABORATORI CHIMICO FARMACOLOGICI SpA
Current assignee: ARCHIFAR LABORATORI CHIMICO FARMACOLOGICI SpA; Pfizer Italia SRL
Priority date: 1978-06-09
Filing date: 1978-05-30
Publication date: 1980-11-11
Also published as: CH633014A5; GB1603127A; NL7806659A; NL182564C; FR2426690A2; SE7805863L; JPH0114238B2; NL950028I2; JPS557203A; BE870570R; SE441751B; FR2426690B2; NL182564B; NL950028I1

Abstract

ABSTRACT OF THE DISCLOSURE:

The present invention relates to novel Rifamycin compounds of formula I;

Description

~ 3 This invention relates to novel RiPamycin com~ound~
having high antibiotic activity.
Canadian Patent application No. 254253 in the name of Archifar Industrie Chimiche del ~rentino S.p.A. of which the pre~ent Applicants are succe~sors in right, discloses compound~ which are obtained by reaoting 3-amino-4-desoxo-4~imino-rifamycin S wi~h ketone~.
~ he Rifamycin compounds according to the aboYe mentioned patent application have antibacterial activity in vitro on ~ram-po~itive, ~ram-negative and particularly on Mycobacterium Tuberculosi~.
The in vitro activity tests on mice infected by intra-venou~ route with Mycobacterium Tuberculosis ~howed that the Rifamycin compounds oP formula I obtained by reacting 3-amino-4 -de~oxo-4-imino-rifamycin S of formula II with ~-piperidones oP
formula III
Reaction 5cheme ~-.` ~
C~3 C~13 H c\
Cl1,07j~ +~

ç~a~ 1, R
b ~ ~ ( III ) .
~H 3 t:' (II) --1-- ,.. ,~ : ~ :

' ,.,.,.. , , . ,. ~

9~5~
3~ ~

H3C ¦ I
33 y~4 OH
~ ~ CH3 O ~ ~ ~

(I) wherein R is a radical selected from the group consisting of hydro- ~:
gen, linear C4-C8 alkyl, branched C3-C8 alkyl, C3-C4 alkenyl ~`
C3-C6 cycloalkyl, C7-C8 cycloalkyl-alkyl, C3-C7 alkoxyalkyl, C5-C6 alkyl-furyl, C -C alkyl-tetrahydrofuryl, C -C
~ 5 6 5 6 alkanoyl, : C2-C6 monohaloalkanoyl, and Y is -H or -COCH3, differ from the ` ;~
derivatives obtained by reacting 3-amino-4-desoxo-4-imino-rifa-~ycin S with ketones other than 4-piperidones in respect of whlch they have a much higher therapeutic activity. . .~
Among the derivatives obtained from 4-piperidones and .: :.
claimed in the previous patent application No. 254253, the Rifamycin compounds of formula I, obtained by reacting a Rifa- ~.
mycin compounds of formula II with N-ethyl-4-piperidone and . ~:
hereinafter shortly called "ethylderivative", proved to have the highest therapeutic activity. . .
The compounds claimed in patent application No. 254253 were obtained by reacting a Rifamycin compounds of formula II -;~
with 4-piperidones of formula III having up to three C atoms ~:~
for R=alkyl, up to eight C atoms for R - arylalkyl and up to 108~ 53 four C a~oms f~r R = acyl.
No other 4-substituted-piperidones had been used.
Recently present applicants have u~ed oth~r 4-substituted~
piperidones (some of which unkno~l at the date of filing of the first application and the Rifamycin compounds of formula I thus o~tained were found to have therapeutic activity surprisingl~
higher than that of Rifamycin compounds of formula I obtained by using 4-piperidones described in the above mentioned patent application No. 254253.
In order to point out these differences o~ the therapeu-tio acti~ity "in vi~o", white mice CDl were infected with Myco-bacteriu~ Tuberculosis H37RV culture by intravenous route. 0.2 ml of above mentioned culture, containing twice as ID50~ were injec-ted into 0ach mouse.
~ hree days after the mice were infected7 ~hey were treat-ed by oral route with Rifamycin compound~ at doses ranging from 20 to 1.25 mg/Kg. Groups of fifteen mice were treated with each Rifamycin compound with single dail~ doses, ~or ~ive days in succession and during ~ix weeks. ~
At the end o~ the treatments ~he deaths were registered and the PD50 was calculated.
~ he animals were kept under observation during about two months.
~ he "ethylderivative" PD50 resulted to be 20 mg/Kg.

,, ., ,~, . . . . . . . . . . . . .
.~ . ~ . . . .. . . . . .. ;
, . . . . . .
. . .

. .. . . . . , -s~
I' A B L E
A c t i v i t y _ ___ R In vitro In vivo MIC ~g/ml PD5~ms/

, n-butyl 0.0005 5 n-hexyl Q.00Q5 10 ~;
allyl 0.0012 5 i-butyl 0.a012 2.6 methyl-allyl 0.005 5 -~
sec-butyl o.oQ5 3.

2-methyl-furyl Q.0012 1,2-dimethyl-propyl 0.005 2.5 ....
n-pentyl 0.00]2 5 ~- `
1,3-dimethyl-butyl 0.0012 205

3-pentyl 0.Q012 2.5 ethyl 0.01 2~ -The results obtained through these experiments with -~
the "ethylderivative" and with some others of the new compounds are : .
reported in ta~le I and demonstrate that the new derivatives having general formula I wherein R is a radical selected from the group consisting of linear C4-C8 alkyl, branched C3-C8 alkyl, C3-C4 alkenyl, C3-C6 cycloalkyl, C7-C8 cycloalkyl-alkyl, C3-C7 alkoxy-alkyl, C5-C6 alkyl-furyl , C5-C6 alkyl-tetrahydrofuryl, C5-C6 alkanoyl, C2-C6 monohaloalkanoyl, hydrogen, and Y is -H or -COCH3, have a PD50 surprisingly lower than the "ethylderivative"
and therefore are more effective than the ethylderivative and consequently of all the compounds covered by patent application ;
No. 2542S3.
Some unrestrictive embodiments o~ the invention will now be described in the following examples.
-,

- 4 - ~ ~ ~

39'1L~3 ~X~MPL~ l 8 g 3-amino-4-deoxo-4-imino-rifamycin S were dissolved in 40 ml dichloromethane and reacted with 2.6 y 1-n-hexyl~4-pipe-ridone at ~5C for 48 hours. The solution was cliluted with 600 ml ethyl ether, filtered and washed with water.
The organic phase was dried on sodium sulphate and then evaporated to dryness. The residue was extracted with ligroin and the violet solution evaporated to dryness.
Yield: 2.5 g product of formula (I), wherein Y is -COCH3, and R is a n-hexyl radical.
The electronic absorption spectrum in methanol shows peaks at 497, 314, 278 and 239 nm.

8 g 3-amino-4-deoxo-4-imino-riEamycin S were dissolved in 40 ml tetrahydrofuran. 4g 1-(1',3'-dimethyl) butyl-4-pipe-ridone, 0.5 g zinc and 0.5 g ammonium acetate were added and the mixture ~as stirred at room temperature for 30 minutes.
The reaction mixture was worked up as in -the example No. 1 obtaining 3.5 g of a product of formula (I), wherein Y is -COCH3 and R is a 1,3-dimethyl-butyl radical. The electronic absorption spectrum in methanol shows peaks at 500, 315, 277 and 240 nm.

8 g 3-a~ino-4-deoxo-4-imino-rifamycin S were dissolved in 40 ml tetrahydrofuran. 1.8 g 1-methallyl-4-piperidone, `~
0.2 g zinc and 0.2 g ammonium acetate were added and the mi~ture was allowed to stand at ~5C for one night.

- 5 -:: :
.,, . '~`; :

.. . -- - .. ~ . - . .

9~53 Reaction mixture was worked up as in -the example No. 1 obtaining 5.5 g product of formula ~I), wherein Y is -COCH3, and R is a methallyl radical.

The elec-tronic absorption spectrum in methanol shows peaks at 498,313,275 and 238 nm.

EXP~IPLE 4 ~
~.; ... .
8 g 3-amino-4-deoxo-4-imino-rifamycin S were dissolved in 40 ml tetrahydrofuran. 3 g 1-cyclohexyl-4-piperidone, 0.2 g zinc and 0 2 ammonium acetate were added -, :
and the mixture was stirred 2.5 hours at room temperature.

Unreacted zinc was filtered and the solution diluted with 1000 ml ethyl ether. ;
. .: - .:
The ethereal solution was washed with buf~er sodium ;~
phosphate solution at pH 7.8 and then extracted with diluted acetic acid. The violet aqueous solution was extracted with ~ ~;
chloroform, the organic phase was washed with water and then dried on sodium sulfate. The chloroform was evaporated to dryness.
- 20 Yield: 3.8 g product of formula (I), wherein Y is -COCH3 and R is a cyclohexyl radical.
The electronic absorption spectrum in methanol shows ;
peaks at 498, 312, 273 and 235 nm.

EX~MPLE S
~ . j ., 8 g 3-amino-4-deoxo-4-imino-rifamycin S were dissolved ~ ~;

in 40 ml tetrahydrofuran. 0.5 g zinc, 0.5 g ammonium acetate -, : :
and 5.5 g 1-(methyl-furyI)-4-piperidone were added and the mixture was stirred at room temperature for 24 hours.

The reaction mixture was filtered, diluted with 500 ml diethyl ether and washed with water. ~ ;
.

- 6 - ~
- ' ~ ' '.:

l~9~S~
The organic phase was concentrated at 250 ml and then extracted with aqueous diluted acetic acid.
The violet, aqueous solution was extracted with dichloromethane and the organic phase, washed with water and dried on sodium sulfate was evaporated to dryness.
Yield: 3.3 g product of formula (I) wherein Y is -COCH3 and R is a methyl-furyl radical.
The electronic absorption spectrum in methanol shows peaks at 497, 316, 276 and 240 nm.

'~

8 g 3-amino-4-deoxo-4-imino-riamycin S were dissolved in 40 ml tetrahydrofuran and dropped at 50C in a mixture of 15 ml tetrahydrofuran, 5 ml acetic acid, 1 g zinc and 5 g l-(methyl-tetrahydrofuryl)-4-piperidone.
Heating is continued for 30 minutes and then the ;/- ;
reaction mixture was worked up as in the example No. 5. ~;
Yield: 2.1 g product of formula (I),wherein Y is ~
-COCH3 and R is a methyl-tetrahydrofuryl radical. - ;
The electronic absorption spectrum in methanol shows ~
... ~, ..
peaks at 495, 314, 275 and 23g nm.

32 g 3-amino-4-deoxo-4-imino-rifamycin S were dissolved - ~, in 200 ml tetrahydrofuran. 9 g 4-piperidone monohydrate ~ `~
hydrochloride, la g ammonium acetate and 0.4 g zinc were added and the mixture was stirred at room temperature for 12 hours.
The reaction mixture was filtered and dropped into ~ ~

1500 ml diluted acetic acid. A~ter filtration the aqueous ~`
solution was neutralized with sodium bicar~onate at pH 6 and then extractèd twice with dichloromethane. ` `
Yield: 13.4 g product of formula (I), wherein Y is -COCH3 and R is a hydrogen atom.
. ~ .

- 7 - ; ~
-B ~ ~ `
~ ; .

89'~53 The electronic absorption spectrum in methanol shows peaks at 500, 315, 275 and 240 nm.

8 g 3-amino-4-deoxo-4-imino-rifamycin S were dissolved in 50 ml tetrahydrofuran. 0.3 g zinc, 0.3 g ammonium acetate and 2.5 g 1-chloroacetyl-4-piperidone were added and the mixture allowed to react at ~5C for 48 hours.
The reaction mixture was filtered and diluted with 150 ml dichloromethane and 800 ml cyclohexane.
The solution was filtered again, washed with buffer sodium phosphate solution at pH 7.5 and then with water.
The solvent was evaporated under vacuum and the residue was crystallized from cyclohexane.
Yield: 3.2 g product of formula (I), wherein Y is -COCH3, and R is a chloroacetyl radical.
The electronic absorption spectrum in methan~l shows peal~s at 497, 310, 273 and 235 nm.

g~3 8 g 3-amino-4-deoxo 4-imino-rifamycin S were dissolved in 40 ml tetrahydrofura~. 0.5 g zinc, 5 ml acetic acid and 4.5 g l-n-octyl-4-piperidone were added and the mixture was stirred ten minutes at room tempera-ture.
Unreacted zinc wa~ filtered and the ~olution diluted with 700 ml diisopropyl-ether. ~he solution was filtered again and concentrated to 300 ml under vacuum.
300 ml petroleum ether were added and the solution ;was filtered once more~ After evaporation of the ~olvent the oily residue was dissolved in 40 ml methanol and the solution was dropped in 400 ml water.
The obtained precipitate was filtered, washed with water and dried at 40C under vacuum.
Yield: 3.8 g product of formula (I)g ~rherein Y is -COCH3 and R i~ a n-octyl radical.
The electronic ab~orption spectrum in methanol shows peaks at 4979 310, 274 and 236 ~m.

EXAMP~E lO ~
; `~;
16 g 3-am~no-4-deoxo-4-imino-rifamycin S were dissolved in lOO ml tetrahydrofuran. 1 g zinc, 0.5 g ammonium acetate and 8 g 1-(3~-methoxyl) propyl-4-piperidone were added and the mix~
ture was stirred at room temperature for 60 minutes.
~he reaction mixture was filtered, diluted with 1500 ml xylene and wa~hed with water. ~he organic pha~e was extracted with diluted acetic acid and then discharged. `
~he aqueou~ solution, buffered at pH 7 with ~odium phos~
phate solution, was extracted with dichloromethane.
After dilution with petroleum ether the violet solution ;was filtered and then ev~porated to dxyness. ~ield: 3-0 g ~:' _g_ .; :

~' '~O~g~1LS~

product o~ formula (I), wherein Y is -COCH3, and R i~ a 3-methoxy~propyl radical. :
~ hin layer chromatography on silica gel plates~ u~ing chloxoform-metha~ol 9:1 a~ mobile phaYe, showed one violet spot with Rf - 0.48.

.. .

8 g 3-amino-4-deoxo-4-imino-rifamycin S were di~solved in 40 ml tetrah~drofuran. 0.5 g zinc, 0.5 g ammonium acetate '' and 4.5 g 1-(1',4'-dimethyl) pentyl-4-piperidone w~re added and the mixture was stirred at room te~perature for 30 minutes.
The reaction mixture was worked up as in'the example No. 10, Yield: 5.0 g produc~ of formula (I) wherein Y is -coaH3 aYld R is a 1,4-dime'thyl-pentyl radical.
~hin layer chromat~graphy on silica gel plates~ using chloroform-methanol 9:1 as mobile phase, showed one ~iolet spot with Rf _ 0.52, EX~MPIE 12 .
8 g 3-amino-4-deoxo-4-imino-rifamycin S were dissolved' in 50 ml tetrahydrofuran. 0.2 g zinc, 0.2 g ammonium acetate a~d 3 g 1-pivaloyl-4-piperidone were added and the mixture was kept a~ O~C for 3 days. ~he reaction mlxture was filtered, dilu-ted with 300 ml diethyl ether and washed with buffer sadium phos~
phate solution at pH 7.5. ~he organic phase was washed with ~ ;
water, dried on sodium sul~ate and evaporated to dryness~
~he residue was o~ystalli-~ed ~rom cyclohexane.
Yield: 7 g product of formula (I) wherein Y is -COCH

-10~

1~9~5;~

~d R is a pivaloyl radical.
'~he electronio ab30rption cpectrum in methanol ~how~
peaks at 497, 316, 276 and 238 nmO

,:

"` '.

: ~:
' -:

: - ~. ~ . , ,'~, "'~''.

)8~4S3 SUPPLEM~NTARY DISCLOSUR~

Operating in the same manner as described in example 1 but making use of 1-n-pentyl-4-piperidone as the reagent,a compound of formula (I) is obtained in which Y is -COCH3 and R is a n-pentyl radical. The electronic absorption spectrum in methanol shows peaks at 500, 316, 278 and 240 nm.

EX~MPLE 1 4 Operating in accordance with the process described in example 2 but making use of 1-(1-ethyl)-propyl-4-piperidone as the reagent, a compound is obtained in which Y is -COCH3 and R is a 3-pentyl radical. The electronic absorption spectrum in methanol shows peaks at 500, 315, 276 and 240 nm.

EXAMPLE 15 `
:,:

Operating in the same manner as described in example 3 `
but using l-allyl-4-piperidone as the reagent, a compound of ;~
formula (I) is obtained in which Y is -COCH3 and R is allyl.
The electronic absorption spectrum of this compound shows peaks at 491,314,276 and 235 nm.

EXA~qPLE 16 Operating according to the process described in example 5 but making use of 1-n-butyl-4-piperidone as the reagent, a compound of formula (I) is obtained in which Y is -COCH3 and R is a n-butyl radical. The electronic absorption -~
spectrum in methanol shows peaks at 496, 317, 276 and 240 nm.
In a similar manner compounds of formula (I) are obtained in ~1 :

lO~ lS;~
ch Y is -COC~{3 and R is an i-butyl or sec-butyl radical.
For R = i-butyl the electronic absorption spectrum in methanol shows peaks at 493, 315, 274 and 238 nm. For R = sec-butyl the peaks are at 500, 315, 275 and 240 nm.

,:
Operating in the same manner as described in example 6 but using 1-(1,2 dimethyl)~propyl-4-piperidone as reagent a compound of formula (I) is ob-tained in which Y is -COCH3 and 10 R is a 1,2-dimethyl-propyl radical. ~ -``,`~', '.', ' ',',' '~'.

~ 13 -:,~

Claims

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. Process for the production of rifamycin compounds of formula I :
(I) wherein R is a radical selected from the group consisting of hydrogen, linear C4- C8 alkyl, branched C3-C8 alkyl, C3-C4 alkenyl, C3-C6 cycloalkyl, C7-C8 cycloalkyl-alkyl, C3-C7 alkoxyalkyl, C5-C6 alkyl-furyl, C5-C6 alkyl-tetrahydrofuryl, C5-C6 alkanoyl, C2-C6 monohaloalkanoyl, and Y is -H or -COCH3, which comprises reacting a compound of formula II :

(II) wherein Y has the above meaning, with a 4-piperidone of formula III:

(III) wherein R has the above meaning.

2. Process according to claim 1, which comprises reacting 3- amino-4-deoxo-4-imino-rifamycin S with 1-n-hexyl-4-piperidone to obtain a compound of formula (I) wherein Y is -COCH3 and R is a n-hexyl radical.

3. Process according to claim 1, which comprises reacting 3-amino-4-deoxo-4-imino-rifamycin S with 1-(1',3'-dimethyl) butyl-4-piperidone to obtain a compound of formula (I) wherein Y
is -COCH3 and R is a 1,3-dimethyl-butyl radical.

4. Process according to claim 1, which comprises reacting 3-amino-4-deoxo-4-imino-rifamycin S with 1-methallyl-4-piperidone to obtain a compound of formula (I) wherein Y is -COCH3 and R is a methallyl radical.

5. Process according to claim 1, which comprises reacting 3-amino-4-deoxo-4-imino-rifamycin S with 1-cyclohexyl-4-piperidone to obtain a compound of formula (I) wherein Y is -COCH3 and R is a cyclohexyl radical.

6. Process according to claim 1, which comprises reacting 3-amino-4-deoxo-4-imino-rifamycin S with 1-(methyl-furyl)-4-piperidone to obtain a compound of formula (I) wherein Y is -COCH3 and R is a methyl-furyl radical.

7. Process according to claim 1, which comprises reacting 3-amino-4-deoxo-4-imino-rifamycin S with 1-(methyl-tetrahydrofuryl)-4-piperidone to obtain a compound of formula (I) wherein Y is -COCH3 and R is a methyl-tetrahydrofuryl radical.

8. Process according to claim 1, which comprises reacting 3-amino-4-deoxo-4-imino-rifamycin S with 4-piperidone monohydrate hydrochloride to obtain a compound of formula (I) wherein Y is -COCH3 and R is a hydrogen atom.

9. Process according to claim 1, which comprises reacting 3-amino-4-deoxo-4-imino-rifamycin S with 1-chloroacetyl-4-piperidone to obtain a compound of formula (I) wherein Y is -COCH3 and R is a chloroacetyl radical.

10. Process according to claim 1, which comprises reacting 3-amino-4-deoxo-4-imino-rifamycin S with 1-n-octyl-4-piperidone to obtain a compound of formula (I) wherein Y
is -COCH3 and R is a n-octyl radical.

11. Process according to claim 1, which comprises reacting 3-amino-4-deoxo-4-imino-rifamycin S with 1-(3'-methoxy) propyl-4-piperidone to obtain a compound of formula (I) wherein Y
is -COCH3 and R is a 3-methoxy-propyl radical.

12. Process according to claim 1, which comprises reacting 3-amino-4-deoxo-4-imino-rifamycin S with 1-(1',4'-dimethyl) pentyl-4-piperidone to obtain a compound of formula (I) wherein Y is -COCH3 and R is a 1,4-dimethyl-pentyl radical.

13. Process according to claim 1, which comprises reacting 3-amino-4-deoxo-4-imino-rifamycin S with 1-pivaloyl-4-piperidone to obtain a compound of formula (I) wherein Y is -COCH3 and R is a pivaloyl radical.

14. Rifamycin compounds having the formula I :

(I) wherein R is a radical selected from the group consisting of hydrogen, linear C4-C8 alkyl, branched C3-C8 alkyl, C3-C4 alkenyl, C3-C6 cycloalkyl, C7-C8 cycloalkyl-alkyl, C3-C7 alkoxyalkyl, C5-C6 alkyl-furyl, C5-C6 alkyl-tetrahydrofuryl, C5-C6 alkanoyl, C2-C6 monohaloalkanoyl, and Y is -H or -COCH3, whenever obtained by a process according to claim 1 or its obvious chemical equivalents.

15. Rifamycin compound according to claim 14, wherein Y
is -COCH3 and R is a n-hexyl radical whenever obtained by a process according to claim 2 or its obvious chemical equivalents.

16. Rifamycin compound according to claim 14, wherein Y
is -COCH3 and R is a 1,3-dimethyl-butyl radical whenever obtained by a process according to claim 3 or its obvious chemical equivalents.

17. Rifamycin compound according to claim 14, wherein Y is -COCH3 and R is a methallyl radical whenever obtained by a process according to claim 4 or its obvious chemical equivalents.

18. Rifamycin compound according to claim 14, wherein Y is -COCH3 and R is a cyclohexyl radical whenever obtained by a process according to claim 5 or its obvious chemical equivalents.

19. Rifamycin compound according to claim 14, wherein Y is -COCH3 and R is a methyl-furyl radical whenever obtained by a process according to claim 6 or its obvious chemical equivalents.

20. Rifamycin compound according to claim 14, wherein Y is -COCH3 and R is a methyl-tetrahydrofuryl radical whenever obtained by a process according to claim 7 or its obvious chemical equivalents.

21. Rifamycin compound according to claim 14, wherein Y is -COCH3 and R is hydrogen whenever obtained by a process according to claim 8 or its obvious chemical equivalents.

22. Rifamycin compound according to claim 14, wherein Y is -COCH3 and R is a chloroacetyl radical whenever obtained by a process according to claim or its obvious chemical equivalents.

23. Rifamycin compound according to claim 14, wherein Y is -COCH3 and R is a n-octyl radical whenever obtained by a process according to claim 10 or its obvious chemical equivalents.

24. Rifamycin compound according to claim 14, wherein Y is -COCH3 and R is a 3-methoxy-propyl radical whenever obtained by a process according to claim 11 or its obvious chemical equivalents.

25. Rifamycin compound according to claim 14, wherein Y is -COCH3 and R is a 1,4-dimethyl-pentyl radical whenever obtained by a process according to claim 12 or its obvious chemical equivalents.

26. Rifamycin compound according to claim 14, wherein Y is -COCH3 and R is a pivaloyl radical whenever obtained by a process according to claim 13 or its obvious chemical equivalents.

CLAIMS SUPPORTED BY THE SUPPLEMENTARY DISCLOSURE

27. Process according to claim 1, which comprises reacting 3-amino-4-deoxo-4-imino rifamycin S with 1-n-pentyl-4-piperidone to obtain a compound of formula (I) wherein Y is -COCH3 and R is a n-pentyl radical.

28. Process according to claim 1, which comprises reacting 3-amino-4-deoxo-4-imino-rifamycin S with 1-(1-ethyl)-propyl-4-piperidone to obtain a compound of formula (I) wherein Y
is -COCH3 and R is a 3-pentyl radical.

29. Process according to claim 1, which comprises reacting 3-amino-4-deoxo-4-imino-rifamycin S with 1-allyl-4-piperidone to obtain a compound of formula (I) wherein Y is -COCH3 and R is allyl.

30. Process according to claim 1, which comprises reacting 3-amino-4-deoxo-4-imino-rifamycin S with 1-n-butyl-4-piperidone to obtain a compound of formula (I) wherein Y is -COCH3 and R is an i-butyl or sec-butyl radical.

31. Process according to claim 1, which comprises reacting 3-amino-4-deoxo-4-imino-rifamycin S with 1-(1,2-dimethyl)-propyl-4-piperidone to obtain a compound of formula (I) wherein Y is -COCH3 and R is a 1,2-dimethyl-propyl radical.

32. Rifamycin compound according to claim 14, wherein Y is -COCH3 and R is a n-pentyl radical whenever obtained by a process according to claim 27 or its obvious chemical equivalents.

33. Rifamycin compound according to claim 14, wherein Y is -COCH3 and R is a 3-pentyl radical whenever obtained by a process according to claim 28 or its obvious chemical equivalents.

34. Rifamycin compound according to claim 14, wherein Y is -COCH3 and R is allyl whenever obtained by a process according to claim 29 or its obvious chemical equivalents.

35. Rifamycin compound according to claim 14, wherein Y is -COCH3 and R is an i butyl or sec-butyl radical whenever obtained by a process according to claim 30 or its obvious chemical equivalents.

36. Rifamycin compound according to claim 14, wherein Y is -COCH3 and R is a 1,2-dimethyl-propyl radical whenever obtained by a process according to claim 31 or its obvious chemical equivalents.