CA2374632A1 - Cyclo-imino depsipeptides and their utilization in controlling endoparasites - Google Patents

Cyclo-imino depsipeptides and their utilization in controlling endoparasites Download PDF

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Publication number
CA2374632A1
CA2374632A1 CA002374632A CA2374632A CA2374632A1 CA 2374632 A1 CA2374632 A1 CA 2374632A1 CA 002374632 A CA002374632 A CA 002374632A CA 2374632 A CA2374632 A CA 2374632A CA 2374632 A1 CA2374632 A1 CA 2374632A1
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Prior art keywords
alkyl
optionally substituted
hetaryl
methyl
aryl
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CA002374632A
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French (fr)
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Peter Jeschke
Achim Harder
Georg Von Samson-Himmelstjerna
Gerhard Bonse
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Bayer AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Hydrogenated Pyridines (AREA)

Abstract

The invention relates to cyclo-imino depsipeptides of formula (I), especiall y 24-membered cyclo-imino depsipeptides. The invention also relates to methods for their preparation and to their utilization in controlling endoparasites.

Description

Le A 33 687Forei~n Countries Th/wa/NT

Novel cvcloiminodepsiuentides, processes for their preparation and their use for controlling endoparasites The present invention relates to cycloiminodepsipeptides, in particular 24-membered cycloiminodepsipeptides, to processes for their preparation and to their use for controlling endoparasites.
The interesting backbone modifications of peptides, which are carried out in particular to reduce their lability to enzymatic hydrolysis, include, in addition to the exchange of the amide oxygen for sulfur, without any doubt also the exchange of amide oxygen for an optionally substituted imino grouping.
Naturally occurring peptides having an iminopeptide bond or an amidine grouping in the molecule are extremely rare. Examples which may be mentioned are bottromycin, a peptide antibiotic from Str~tomyces bottropensis, amidinomycin and netropsin (J.
M. Waiswisz et al., J. Am. Chem. Soc. 79, 1957, p. 4520; S. Nakamura Chem.
Pharm. Bull. 9, 1961, p. 641; S. Nakamura et al., J. Antibiot. 17A, 1964, p.
220).
Methods for introducing optionally substituted imino functions into synthetic peptides are known from the literature. Examples which may be mentioned here are ,.....
the syntheses of amidoxime, cyanamidine and amidrazone analogs of chemotactic peptides (G. Sauve et al., Can. J. Chem. 61, 1985, p. 3089). Chemotactic peptides of the N-formyl-methionyl-leucyl-phenylalanine (f Met-Leu-Phe-OR) type are of interest as bioregulator prototypes of immune cells - they induce, for example, the release of lysozyme from human neutrophiles (S. V. Rao et al., Spectroscopy (Ottawa) 4 (3), 1985, p. 153; B. Belleau et al., Int. J. Immunopharmacol. 11 (S), 1989, p. 467; E. Schiffmann et al., Proc. Natl. Acad. Sci. U.S.A. 72, 1975, p.
1059;
R. J. Freer et al., Biochemistry 21, 1982, p. 257). H. A. Moynihan et al. have described a preparation variant of Nw-hydroxy-N'~-methyl-L-arginine, a novel NO
synthase inhibiter (J. Chem. Soc. Perkin Traps. I 1994, p. 769). Suitable starting materials for preparing the iminopeptides mentioned further above are, according to Le A 33 687-Foreig-nn Countries .. -2-G. Sauve et al. or H. A. Moynihan et al., preferably the corresponding endothiopeptides.
Also known is the synthesis of iminodipeptides from corresponding a-amino-nitrites (cf. N-benzyloxycarbonyl-irninodipeptides: W. Ried et al. Chem. Ber. 95, 1962, p. 728; Ann. Chem. 661, 1963, p. 76; T. Yamada et al., Bull. Chem. Soc. Jpn.
50 (5), 1977, p. 1088; analogs of N-phthalyl(iminoglycyl)-(S)-valine: E. Vargha et al.
Studia Univ. Babes-Bolyai, Ser. Chem. 11, 1966, p. 85, ref. Chem. Abstr. 66, 1967, 2757).
Poly(dipeptamidines) in which the carbonyl oxygen of every second peptidic amide group is replaced by an imine nitrogen have been prepared as comparison products for the oligomerization of a-amino-nitrites (cf. A. Eschenmoser et al., Helv.
Chim.
Acta 69, 1986, p. 1224).
In contrast to the processes already mentioned for preparing various N-substituted iminopeptides, nothing has been disclosed concerning the preparation of cycloiminodepsipeptides consisting of amino acids, hydroxyiminocarboxylic acids and optionally hydroxycarboxylic acids, hydroxythiocarboxylic acids.
~...,.
In particular, nothing has hitherto been disclosed concerning the preparation of cycloiminodepsipeptides consisting of amino acids, hydroxyiminocarboxylic acids and optionally hydroxycarboxylic acids, hydroxythiocarboxylic acids as ring building blocks and 24 ring atoms from corresponding cyclothiodepsipeptides.
Cyclic depsipeptides and their preparation and use as endoparasiticides have already been the subject of numerous publications.
A cyclodepsipeptide with the name PF 1022A, for example, and its action against endoparasites is already known (EP-A 382 173 and EP-A 503 538) Le A 33 687-Foreign Countries Further cyclic depsipeptides (cyclooctadepsipeptides: WO 98/55 469;
WO 98/43 965; WO 98/15 523; WO 98/37 088; WO 97/02 256; WO 97/09 331;
WO 96/11 945; WO 95/07 272; WO 94/19 334; WO 93119 053; EP-A 634 408;
EP-A 626 375; EP-A 626 376; EP-A 664 297; EP-A 6:34 408; EP-A 718 298;
WO 97/09 331; cyclohexadepsipeptides: WO 93/25 543; WO 95/27 498;
EP-A 658 551; cyclotetradepsipeptides: EP-A 664 297; dioxomorpholines:
WO 96/38 165; JP 08 225 552) and open-chain depsipeptides (EP-A 657 171;
EP-A 657 172; EP-A 657 173; WO 97/07 093) and their endoparasiticidal action have been described.
Cyclothiodepsipeptides consisting of amino acids, hydroxythiocarboxylic acids and optionally hydroxycarboxylic acids as ring building blocks and 24 ring atoms, their preparation and their use for controlling endoparasites are subject of an earlier patent application (WO 98/43 965) of the applicant.
In addition to the novel cycloiminodepsipeptides, the present invention also provides a process for preparing cycloiminodepsipeptides, in particular cycloiminodepsipeptides consisting of amino acids, hydroxyiminocarboxylic acids and optionally hydroxycarboxylic acids, hydroxythiocarboxylic acids as ring building blocks and 24 ring atoms.
The invention also provides the use of cycloiminodepsipeptides, in particular of cycloiminodepsipeptides consisting of amino acids, hydroxyaminocarbvxylic acids and optionally hydroxycarboxylic acids, hydroxythiocarboxylic acids as ring building blocks and 24 ring atoms for preparing compositions for controlling endoparasites.
The present invention relates in particular to:
1. Cycloiminodepsipeptides of the general formula (I) Le A 33 687-Foreign Countries _4-R'Z O
X ~ ~ R"
~C O
RZ N R~ R~o~N'C~X3 O ~' R9 O O
R3.,_ / O
''~ R4 R~
Ra n) Rs~O~C:Xz [O' R6 in which Rl, R4, R' and R1° independently of one another represent hydrogen, straight-chain or branched alkyl, R2, R5, R8 and R" independently of one another represent hydrogen, optionally substituted straight-chain or branched alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, arylalkyl, hetarylalkyl and also aryl or hetaryl, R1° and R" together with the atoms to which they are attached represent an optionally substituted 5- or 6-membered ring which may optionally be interrupted by oxygen, sulfur, sulfoxy or sulfonyl, R6 and R~Z independently of one another represent hydrogen, optionally substituted alkyl or arylalkyl, and also optionally substituted cycloalkylalkyl, R3 and R9 independently of one another represent hydrogen, optionally substituted straight-chain or branched alkyl, alkenyl, cycloalkyl, alkoxycarbonylalkyl, cycloalkylalkyl, arylalkyl, hetarylalkyl, aryl or hetaryl, Le A 33 687-Foreign Countries and C=X', C=X2, C=X3 and C=X4 independently of one another each represent one of the groups C=O, C=S or CHZ or a group C=N-A, where at least one of the groups C=X~, C=X2, C=X3 and C=X4 must represent C=N-A, in which A represents hydrogen, optionally substituted alkyl, alkenyl, alkinyl, .-..
alkylcarbonyl, alkylsulfonyl, and also cyano, nitro, carbamoyl, alkoxycarbonyl, formyl, -(C=NH)-NH2, -P(O)-O-alkyl, -P(S)-O-alkyl or optionally represents a radical A' -Y-R~3 (A') in which Y represents oxygen, sulfur or -N-R~4, R'3 and R14 independently of one another represent hydrogen, optionally substituted - straight-chain or branched, alkyl, alkenyl, alkinyl, cycloalkyl, cyclo-~""..
alkylalkyl, arylalkyl, hetarylalkyl, aryl or hetaryl and also represent formyl, alkoxydicarbonyl, alkylsulfonyl, haloalkoxyalkylsulfonyl, alkoxycarbonyl, alkylaminocarbonyl, alkenyloxycarbonyl, alkinyloxycarbonyl, aryloxyalkyl, hetarylcarbonyl,alkylcarbonyl or optionally represent a radical from the group consisting of BI, BZ, B3 and B4, Z O
I I
Y
Q ~ G ~ (CNR~s~n- 1 Rya i (B ) (B ) Le A 33 687-Foreign Countries Rz, O
O I
,a~Y,,~'~ O~G~N:
R i~ II R R
,s R2o R (B3) Z (8a) in which Q represents optionally substituted straight-chain or branched alkyl, alkenyl, alkinyl, cycloalkyl, alkoxy, alkenyloxy, alkinyloxy, cycloalkoxy, aryloxy, arylalkoxy, hetaryloxy, hetarylalkoxy, alkylthio, alkenylthio, alkinylthio, cycloalkylthio, arylthio, arylalkylthio, hetarylthio, hetarylalkylthio, alkyl-amino, alkenylamino, alkinylamino, cycloalkylamino, arylamino, arylalkyl-amino, hetarylamino, hetarylalkylamino, dialkylamino, dialkenylamino, aryl, arylalkyl, hetaryl or hetarylalkyl, cyano, amino or an optionally substituted cyclic amino group which is attached via nitrogen, Z
I I
G
~'' represents carboxyl, thiocarboxyl, sulfoxy, sulfonyl, -P(O)-O-alkyl, , -P(S)-O-alkyl or -C=N-Rls, R's represents hydrogen, hydroxyl, alkoxy, alkylcarbonyl, alkoxycarbonyl, haloalkylcarbonyl, alkylsulfonyl, nitro or cyano, R'6 represents hydrogen or alkyl, n represents 0, 1 or 2, Y' represents oxygen or sulfur or -N-R'7, R~8 represents, if YI represents nitrogen, a cyclic amino group which is attached via this nitrogen atom, Le A 33 687-Foreign Countries _7_ R" and R~g independently of one another represent hydrogen, optionally substituted straight-chain or branched alkyl, alkenyl, alkinyl, cycloalkyl, cycloalkylalkyl, alkoxycarbonyl, aryl, arylalkyl, hetaryl or hetarylalkyl, or S R1' and R'8 together with the adjacent N atom represent an optionally substituted heterocyclic 4-, 5-, 6- or 7-membered ring system or represent an optionally substituted 7- to 10-membered bicyclic ring system which may optionally also be interrupted by oxygen, sulfur, sulfoxyl, sulfonyl, carbonyl, -N-O, -N=, -NR22 or by quaternary nitrogen, R19 and RZ° independently of one another represent hydrogen, straight-chain or branched alkyl, alkenyl, cycloalkyl and also optionally substituted aryl, arylalkyl, hetaryl, hetarylalkyl, or R19 and RZ° together represent an optionally substituted spirocyclic ring, R2° and RZ~ together with the atoms to which they are attached represent an optionally substituted 5-, 6- or 7-membered ring which may optionally be interrupted by oxygen, sulfur, sulfoxyl, sulfonyl, R2' represents hydrogen, optionally substituted straight-chain or branched alkyl, cycloalkyl, arylalkyl, hetarylalkyl, and also aryl or hetaryl, R22 represents hydrogen, optionally substituted straight-chain or branched alkyl, alkenyl, alkinyl, cycloalkyl, cycloalkylalkyl, alkoxycarbonyl, alkylcarbonyl, cycloalkylcarbonyl, cyano, arylalkyl, hetaryialkyl, and also aryl or hetaryl, R13 may also represent a protective group which can be removed selectively, or a polymeric support which is attached to Y via an anchor group which can be removed selectively, Le A 33 687-Foreign Countries _g_ and to the pure optical isomers, racemates and physiologically acceptable salts thereof, for controlling endoparasites in medicine and veterinary medicine.
Depending on the nature of the substituents, the compounds of the general formula (I) can exist as geometrical and/or optical isomer mixtures and also as mixtures of regioisomers of varying compositions. The invention relates both to the pure isomers and to the isomer mixtures.
Preference is given to the cycloiminodepsipeptides consisting of amino acids, hydroxyiminocarboxylic acids and optionally hydroxycarboxylic acids, hydroxythiocarboxylic acids as ring building blocks and 24 ring atoms of the general formula (I) 1~
R' Z O
X'~ ,~ R"
~C O
R2 N R~ R,o N~C=Xa Ra O O
Rs l O
R4 R' RB (I) Rs~O~C:Xz IOI ~R6 in which R', R4, R' and R~° represent straight-chain or branched C»-alkyl, in particular 2U methyl, RZ, R5, R8 and RBI independently of one another represent Ci.~-alkyl, in particular isobutyl, Le A 33 687-Foreign Countries R6 and R12 independently of one another represent optionally substituted C,~-alkyl or aryl-C,_2-alkyl, in particular optionally substituted benzyl, R3 and R9 independently of one another represent optionally C,.~-alkyl, S hetaryl-C,_2-alkyl, C,-C4-alkoxycarbonylmethyl, aryl-C,_2-alkyl, in particular optionally substituted benzyl, substituents that may be mentioned being hydrogen, halogen, cyano, carbamoyl, Cite-alkyl, hydroxyl which carries a protective group or unprotected hydroxyl, C i _g-alkoxy, C 1 ~,-alkoxy-C, ~,-alkoxy, Cz.~-alkenyloxy, hetaryl-CL~-alkoxy, where the heterocycles for their part may be substituted, nitro, or IS
a radical from the group consisting of R23R24N_CI-C6_alkoxy, R23R24N-C1_Cg-alkyl, NR23R24 and -SOZ-NR23R24, in which R23 and R24 independently of one another each represent hydrogen, C~-C6-alkyl, CI-C6-alkoxy-C~-C6-alkyl, C3-C~-cycloalkyl, C3-C~-cycloalkylamino-C~-C6-alkyl, wherein the cycloalkyl ring one or more carbon atoms may also be replaced by nitrogen, oxygen or sulfur atoms, hetaryl-C1-C4-alkyl or a protective group, or R23 and R24 together with the nitrogen atom to which they are attached represent hetaryl or heterocycloalkyl, in particular N
pyrrolidino, N-piperazino, N-morpholino, N-thiomorpholino, N-piperidino, N-imidazolo, 2-oxo-pyrrolidinyl, phthalimino or tetrahydrophthalimino, Le A 33 687-Foreign Countries - 1p _ and ( i ) C=X' represents a group C=N-A, C=Xz, C=X3 and C=X4 represent C=O, C=S or CHZ, or ( iii ) C=X3 represents a group C=N-A, C=X1, C=X2 and C=X4 represents C=O, C=S or CHZ, or ( iv ) C=X' and C=X3 represent a group C=N-A, C=X2 and C=X4 represent C=O, C=S or CHZ, in which A represents hydrogen, optionally substituted C,~-alkyl, C2.~-alkenyl, C2_ 4-alkinyl, C1-C4-alkylcarbonyl, C,_6-alkylsulfonyl and also cyano, 2U nitro, carbamoyl, CZ_6-alkoxycarbonyl, formyl, -(C=NH)-NH2, -P(O)-O-C,_3-alkyl, -P(S)-O-CI_3-alkyl or optionally represents a radical A1 I'-R~3 (A~) where Y represents oxygen or -N-R~4, R'3 and R~4 independently of one another represent hydrogen, optionally substituted straight-chain or branched C1_8-alkyl, C2_g-alkenyl, C2_$
alkinyl, C3_~-cycloalkyl, C3_~-cycloalkyl-C,_2-alkyl, aryl-C1_2-alkyl, Le A 33 687-Foreign Countries hetaryl-C,_z-alkyl, aryl or hetaryl and also formyl, C~-Cg-alkylsulfonyl, C~-C2-haloalkoxy-Ct-2-alkylsulfonyl, C~-Cg-alkylcarbonyl, C1-Cg-alkoxycarbonyl, C1-Cg-alkylaminocarbonyl, C2-Cg-alkenyloxy-carbonyl, C2-C$-alkinyloxycarbonyl, aryloxy-Ct-CZ-alkyl, hetaryl-carbonyl, Cite-alkoxydicarbonyl or optionally represent a radical from the group consisting of B1, B2, B3 and B4 Z O
II tt Y
Q~G~(CHR'6)n- ~ R,si ~,"is~
(B ) O (Bz) R2~ O
O I 'I
,siY~ Q
R i~ I ( ' 9 Ri''''o R~9 Rio (B3) Z R (B4) in which Q represents optionally substituted straight-chain or branched C1_g-alkyl, C2_g-alkenyl, C2_g-alkinyl, C3_~-cycloalkyl, C,_6-alkoxy, C2_6-- alkenyloxy, C2~-alkinyloxy, C3_~-cycloalkoxy, aryloxy, aryl-C,_2-_., alkoxy, hetaryloxy, hetaryl-Ci_2-alkoxy, C~_6-alkylthio, C2~-alkenyl-thio, C2_6-alkinylthio, C3_~-cycloalkyl-thio, arylthio, aryl-C1_2-alkylthio, hetarylthio, hetaryl-Ci_2-alkylthio, C~_6-alkylamino, C2~-alkenylamino, CZ_6-alkinylamino, C3~-cyclo-alkylamino, arylamino, aryl-C,_2-alkyl-amino, hetarylamino, hetaryl-CI_Z-alkylamino, di-C,~-alkylamino, di-C2.~-alkenylamino, aryl, aryl- C1_2-alkyl, hetaryl, hetaryl-C~-C2-alkyl and also cyano, amino or an optionally substituted cyclic amino group which is attached via nitrogen, Z
I I
G
~ ~ represents thiocarboxyl or carboxyl, Le A 33 687-Foreign Countries R15 represents hydrogen, hydroxyl, C1.~-alkoxy, C»-alkylcarbonyl, Ci.~-alkoxycarbonyl, halogeno-C,.~-alkylcarbonyl, CIA-alkylsulfonyl, nitro or cyano, R~6 represents hydrogen or C~.~-alkyl, n represents 0, 1 or 2, Y' represents oxygen, sulfur or -N-R~~, RIg represents, if Y1 represents nitrogen, a cyclic amino group which is attached via this nitrogen atom, R~~ and R~g independently of one another represent hydrogen, optionally substituted straight-chain or branched Cite-alkyl, CZ~-alkenyl, C2~-alkinyl, C3_~-cycloalkyl, C3_~-cycloalkyl-C1~-alkyl, C~_6-alkoxycarbonyl, aryl, aryl-CI_Z-alkyl, hetaryl, hetaryl-C,_2-alkyl, or R" and R1g together with the adjacent N atom represent an optionally substituted ~ heterocyclic 4-, 5-, 6- or 7-membered ring system or represent an optionally 7- to 10-membered bicyclic ring system which may optionally also be interrupted by oxygen, sulfur, sulfoxyl, sulfonyl, carbonyl, -N-O, -N=, -NR22 or by quaternary nitrogen, R~9 and R2° independently of one another represent hydrogen, optionally substituted straight-chain or branched CL~-alkyl, CZ_6-alkenyl, (:3_~-cycloalkyl and also optionally substituted aryl, aryl-C1_2-alkyl, hetaryl, hetaryl-C,_2-alkyl, or R~9 and R2° together represent an optionally substituted spirocyclic ring, Le A 33 687-Foreign Countries RZ° and R2~ together with the atoms to which they are attached represent an optionally substituted S-6- or 7-membered ring which may optionally be interrupted by oxygen, sulfur, sulfoxyl, sulfonyl, S R2' represents hydrogen, optionally substituted straight-chain or branched C,~-alkyl, C3.~-cycloalkyl, aryl-C1_2-alkyl, hetaryl-C,_2-alkyl, and also aryl or hetaryl, R22 represents hydrogen, optionally substituted straight-chain or branched C,_6-alkyl, C2~-alkenyl, C2_6-alkinyl, C3_~-cycloalkyl, C3_~-cycloalkyl-C~.~-alkyl, C»-alkoxycarbonyl, C~_6-alkylcarbonyl, C3_~-cycloalkylcarbonyl, cyano, aryl-C,_z-alkyl, hetaryl-Ct_Z-alkyl, and also aryl or hetaryl, 1S R~3 also represents a protective group which can be removed selectively, for example allyl, allyloxycarbonyl (Alloc), benzyl (Bn), benzyloxycarbonyl (Z), tert-butyloxycarbonyl (Boc), tetrahydropyran 2-yl (THP) or fluorenylmethoxycarbonyl (Fmoc) and also represents a polymeric support which is attached to Y via an anchor group which = can be removed selectively, and optical isomers, racemates and physiologically acceptable salts thereof.
The general formula (I) provides a general definition of the cycloiminodepsipeptides 2S according to the invention and their salts.
The cycloiminodepsipeptides according to the invention and their acid addition salts and metal salt complexes have good endoparasiticidal, in particular anthelmintic, action and can preferably be used in the field of veterinary medicine.
2. Process 1 for preparing the novel compounds of the general formula (I) Le A 33 687-Foreign Countries R~2 O
X~~~ ~R~~
O
R2 N N , . X3 ~R~ Rio C.
~R9 O
O O

'( R4 R~
X'~~C'N~ \N R8 ( R II O I C: X2 O R6 and salts thereof, """~' in which RI to R'2 and the groups C=X1 to C=X4 have the meanings given in point 1, characterized in that cyclothiodepsipeptides of the general formula ( I ) R~2 O
X\C~O~R~1 R2 N~R~ io ~C Xs ,"~., R ~
O / _R9 O O
R3_ / O
'( R4 R~
X'~'C'N~ \N R8 (I) R II OYC:X2 O R6 and salts thereof, in which RI to RI2 have the meanings given in point 1, and Le A 33 687-Foreign Countries C=X', C=X2, C=X3 and C=X4 independently of one another represent C=O, C=S or CH2, where at least one of the groups C=X', C=X2, C=X3 and C=X4 has to represent a C=S group, are reacted with amino compounds of the general formula (II}
H2N-A (II) in which A has the meanings given in point 1 in the presence of suitable metal salts or metal oxides, in particular mercury (II) acetate, mercury(II) chloride or mercury(II) oxide, in the presence of a basic reaction auxiliary and in the presence of a suitable diluent.
The process according to the invention relates in particular and preferably to the preparation of the novel cycloiminodepsipeptides of the general formula (Ia) A R~2 O
"~°. N '\C~ O ~ R 11 ~R~ Rio O O

R4 R~
O N~ \N R8 (Ia) R~O~O
O Rs and salts thereof, in which A and R~ to R~z have the meanings given in point 1.

Le A 33 687-Foreign Countries The process 2 according to the invention for preparing the novel and preferred cycloiminodepsipeptides of the general formula (Ia) and salts thereof is characterized in that a) the cyclothiodepsipeptides of the general formula (Ib) or salts thereof, R~2 O
S'C~O~Ro R2 N ' ~N' O
~T. ~R~ Rio O O

~ ~Ra R~
O' -N N R8 ( R~'O~O

in which R' to R'2 have the meanings given in point 1 are reacted with amino compounds of the general formula (II) H2N-A (II) 1 S in which A has the meanings given in point 1 in the presence of suitable metal salts or metal oxides, in particular mercury (II) 2U acetate, mercury (II) chloride or mercury(II) oxide, and in the presence of a basic reaction auxiliary and in the presence of a suitable diluent, or b) for preparing the novel cycloiminodepsipeptides of the general formula (Ia) Le A 33 687-Foreign Countries A R~2 O
N1~C~O~R~~

~R~ Rio O~ R9 O O

,R4 R\
O N N R$ (Ia) R~p~O
O R6 and salts thereof, in which S R1 to R12 have the meanings mentioned in point 1, A represents a radical -Y-R'3 (A'), in which Y has the meaning given in point l, °'~ R'3 represents radicals from the group consisting of B' to B3 O O
I I
/G~(CHR'6)n- R~siYvS\ R~s~Y
Q (B~) O (B2) R,s Rio (B3) in which Z
G
~ , Q, Y', n, R~6, and Rl8-R2° have the meanings given in point 1, Le A 33 687-Foreign Countries the novel cycloiminodepsipeptides of the general formula (Ic) obtained by processes 2a) and 3 according to the invention H~Y R~2 O
N',C~O~R~~
RZ N N O
~R~ Rio O~ R9 O O

R4 R~
O N~ 'N R8 (Ic) and salts thereof, R~O~O

in which Y and R~ to R~2 have the meanings given in point 1, are reacted with compounds of the general formula ( IIIa-c ) Z O O
~~.~ G Rya ~- Y ~ S R, a ~. Y' i w ~s II'W ~W
(CHR )n-W
O (~) R,s Rio (IIIc) in which Z
G
~ , Q, Y', n, R~6, and RI8-RZ° have the meanings given in point 1, W represents a suitable leaving group, such as, for example, halogen, Le A 33 687-Foreign Countries if appropriate in the presence of a catalyst, if appropriate in the presence of a basic reaction auxiliary and if appropriate in the presence of diluents, or c) to prepare the novel cycloiminodepsipeptides of the general formula (Ia) and salts thereof, in which A represents a radical -Y-R'3 (A') in which Y has the meanings given in point 1, R13 represents radicals from the group consisting of B~ and B3 Z O
Y /~

(~ ~ G ~ (CHR'6)n- B~ R R1s R2o ( ) (83) in which Q, Y1, n, R1g-R2° have the meanings given in point 1, n represents 0, Z
G
and the group ~ ~ represents carboxyl, the compounds of the general formula (Ic) and salts thereof Le A 33 687-Foreign Countries H~Y R~2 O
N'C~O~R~~

~R~ Rio O~ R9 O O

R4 R~
O N~ \N R$ (IC) R~O~O

in which Y and R~ to RIZ have the meanings given in point 1 are reacted with a carboxylic anhydride of the general formula (IV) (Q-CO)ZO (IV) in which Q has the meaning given in point 1 or f R,e~Y
R~9 ~R2o represents the radical 1 S in which Yl, R'$-R2° have the meaning given in point 1, if appropriate in the presence of a catalyst, if appropriate in the presence of a basic reaction auxiliary and if appropriate in the presence of diluents, or d) by reacting compounds of the general formula (Ic) Le A 33 687-Foreign Countries a) with amino acid derivatives of the general formula (V) R2~ O
Q~G~N
i~ OH
II R~s Rzo (V) Z
in which S
Z
I I
G
~ , Q, and R'9 to RZ~ have the meaning given in point 1 if appropriate in the presence of coupling agents and if appropriate in the presence of a basic reaction auxiliary and also, if appropriate, in the presence of diluents, or ~3) with compounds of the general formulae (VI) and (VII) Z

i G ~. N=C=Y
Ris-N=C=Y (VI) Y (VII) 15 in which Z
I I
G
~ , Y and R15 have the meaning given in point 1, if appropriate in the presence of a basic reaction auxiliary or a catalyst, if appropriate 20 in the presence of diluents.
The invention furthermore relates to:

Le A 33 687-Foreign Countries 3. Process 3 for preparing cycloiminodepsipeptides of the general formula (Ic) and salts thereof, HAY R~2 O
~Rii O

~R~ Rio O~ R9 O O

R4 R~
O~N~ \N R8 (IC) R~O~O

in which Y and R~ to R12 have the meanings given in pointl, characterized in that a) from the cycloiminodepsipeptides of the general formula (Ia) obtainable according to process 2a and salts thereof, A R~2 O
N'~C~O~R»

R~ Rio O O

/ R4 R;
O N N R8 (Ia) R~O~O

in which Le A 33 6$7-Forei~~n Countries Rl to R12 have the meanings given in point 1, A represents a radical -Y-R~3 (A~), in which Y represents oxygen or -N-H, R13 represents a protective group which can be removed selectively, for example, allyl, allyloxy-carbonyl (Alloc), benzyl (Bn), benzyloxycarbonyl (Z), tert-butyloxycarbonyl (Boc), tetrahydropyran-2-yl (THP) or in fluorenylmethoxycarbonyl (Fmoc), the radical R13 is selectively removed, depending on the removable protective group either in the presence of a hydrogenation catalyst, in the presence of a protic acid or a basic reaction auxiliary and in the presence of a diluent, or b) - from the cycloiminodepsipeptides of the general formula (Ia), attached to a polymeric support, which are obtainable by process 2a, and salts thereof, A R~2 O
~Ro O

~R~ Rio O O

R Ra R7 O N ~ \N R a (Ia) R~O'~O
O 'R6 in which Le A 33 687-Foregn Countries R' to R'2 have the meanings given in point 1, A represents a radical -Y-R'3 (A') in which Y represents oxygen or -N-H, R'3 represents a selectively removable anchor group on a polymeric support, the compounds of the formula (Ic) are released by selective removal of the anchor group from the polymeric support R13 in the presence of a suitable catalyst or in the presence of a protic acid and in the presence of a diluent.
The general formula (I) provides a general definition of the cycloiminodepsipeptides according to the invention and their salts.
The cycloiminodepsipeptides according to the invention and their acid addition salts and metal salt complexes have good endoparasiticidal, in particular anthelmintic, action and can preferably be used in the field of veterinary medicine.
The definitions of terms below apply to all of the general formulae and descriptions mentioned above or below.
Optionally substituted alkyl, alone or as component of a radical in the general formulae, represents straight-chain or branched alkyl having preferably 1 to 6, in particular 1 to 4, carbon atoms. Examples which may be mentioned are optionally substituted methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tent-butyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-methylpentyl, 2-methyl-pentyl, 3-methylpentyl, 4-methylpentyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-Le A 33 687-Foreign Countries dimethylbutyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethylbutyl and ethylbutyl.
Methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl may be mentioned as being preferred.
Optionally substituted alkenyl, alone or as component of a radical in the general formulae, represents straight-chain or branched alkenyl having preferably 1 to 6, in particular 1 to 4, carbon atoms. Examples which may be mentioned are optionally substituted vinyl, 2-propenyl, 2-butenyl, 3-butenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-butenyl, 1,1-dimethyl- 2-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-2-propenyl, hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-2-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dirilethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl and 1-ethyl-2-methyl-2-propenyl.
Optionally substituted ethenyl, 2-propenyl, 2-butenyl or 1-methyl-2-propenyl may be mentioned as being preferred.
Optionally substituted alkinyl, alone or as component of a radical in the general formulae, represents straight-chain or branched alkinyl having preferably 1 to 6, in particular 1 to 4, carbon atoms. Examples which may be mentioned are optionally substituted ethinyl, 2-propinyl, 2-butinyl, 3-butinyl, 1-methyl-2-propinyl, 2-pentinyl, 3-pentinyl, 4-pentinyl, 1-methyl-3-butinyl, 2-methyl-3-butinyl, 1-methyl-2-butinyl, Le A 33 687-Foreign Countries 1,1-dimethyl-2-propinyl, 1-ethyl-2-propinyl, 2-hexinyl, 3-hexinyl, 4-hexinyl, hexinyl, 1-methyl-2-pentinyl, 1-methyl-3-pentinyl, 1-methyl-4-pentinyl, 2-methyl-3 pentinyl, 2-methyl-4-pentinyl, 3-methyl-4-pentinyl, 4-methyl-2-pentinyl, l,l dimethyl-3-butinyl, 1,2-dimethyl-3-butinyl, 2,2-dimethyl-3-butinyl, 1-ethyl-3-butinyl, 2-ethyl-3-butinyl and 1-ethyl-1-methyl-2-propinyl.
Optionally substituted ethinyl, 2-propinyl or 2-butinyl may be mentioned as being preferred.
Optionally substituted cycloalkyl, alone or as component of a radical in the general formulae, represents mono-, bi- and tricyclic cycloalkyl, preferably having 3 to 10, in particular 3, 5 or 7, carbon atoms. Examples which may be mentioned are optionally substituted cyclopropyl, cyclobutyl, cyclopentyl, cyclo-hexyl, cycloheptyl, cyclooctyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl and adamantyl.
Halogenoalkyl, alone or as component of a radical in the general formulae, contains 1 to 4, in particular 1 or 2, carbon atoms having preferably 1 to 9, in particular 1 to S, identical or different halogen atoms, preferably fluorine, chlorine or bromine, in particular fluorine or chlorine. Examples which may be mentioned are trifl~oromethyl, trichloromethyl, chlorodifluoromethyl, dichlorofluoromethyl, chloromethyl, bromomethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 2-chloro-2,2-difluoroethyl, pentafluoroethyl and pentafluoro-tert-butyl.
Optionally substituted alkoxy, alone or as component of a radical in the general formulae, represents straight-chain or branched alkoxy having preferably 1 to 6, in particular 1 to 4, carbon atoms. Examples which may be mentioned are optionally substituted methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy.
Optionally substituted alkoxyalkoxy, alone or as component of a radical in the general formulae, represents 2 alkoxy radicals as mentioned above which are C-O-Le A 33 687-Foreign Countries attached to each other. Examples which may be mentioned are optionally substituted methoxymethoxy, methoxyethoxy, methoxy-n-propoxy and ethoxyisopropoxy.
Optionally substituted alkoxyalkoxyalkoxy, alone or as component of a radical in the general formulae, represents 3 alkoxy radicals as mentioned above which are in each case C-O-attached to each other. Examples which may be mentioned are optionally substituted methoxymethoxyethoxy, methoxyethoxyethoxy and methoxyethoxy-n-propoxy.
Optionally substituted halogenoalkoxy, alone or as component of a radical in the general formulae, represents straight-chain or branched halogenoalkoxy having preferably 1 to 6, in particular 1 to 4, carbon atoms. Examples which may be mentioned are optionally substituted difluoromethoxy, trifluoromethoxy, trichloromethoxy, chlorodifluoromethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2,2,2-trifluoroethoxy and 2-chloro-1,1,2-trifluoroethoxy.
Optionally substituted alkylthio, alone or as component of a radical in the general formulae, represents straight-chain or branched alkylthio having preferably 1 to 6, in particular 1 to 4, carbon atoms. Examples which may be mentioned are optionally substituted methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio and tert-butylthio.
Optionally substituted halogenoalkylthio, alone or as component of a radical in the general formulae, represents straight-chain or branched halogenoalkylthio having preferably 1 to 6, in particular 1 to 4, carbon atoms. Examples which may be mentioned are optionally substituted difluoromethylthio, trifluoromethylthio, trichloromethylthio, chlorodifluoromethylthio, 1-fluoroethylthio, 2-fluoroethylthio, 2,2-difluoroethylthio, 1,1,2,2-tetrafluoroethylthio, 2,2,2-trifluoroethylthio and 2 chloro-1,1,2-trifluoroethylthio.

Le A 33 687-Foreignn Countries Optionally substituted alkylcarbonyl, alone or as component of a radical in the general formulae, represents straight-chain or branched alkylcarbonyl having preferably 1 to 6, in particular 1 to 4, carbon atoms. Examples which may be mentioned are optionally substituted methylcarbonyl, ethylcarbonyl, n propylcarbonyl, isopropylcarbonyl, sec-butylcarbonyl and tert-butylcarbonyl.
Optionally substituted cycloalkylcarbonyl, alone or as component of a radical in the general formulae, represents mono-, bi- and tricyclic cycloalkylcarbonyl, having preferably 3 to 10, in particular 3, 5 or 7, carbon atoms. Examples which may be mentioned are optionally substituted cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl, bicyclo[2.2.1]heptylcarbonyl, bicyclo[2.2.2]octylcarbonyl and adamantylcarbonyl.
Optionally substituted alkoxycarbonyl, alone or as component of a radical in the general formulae, represents straight-chain or branched alkoxycarbonyl having preferably 2 to 7, in particular 2 to 5, carbon atoms. Examples which may be mentioned are optionally substituted methoxycarbonyl, ethoxycarbonyl, n-propoxy-carbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxy-carbonyl and tert-butoxycarbonyl.
Aryl is, for example, a mono-, bi- or polycyclic aromatic radical, such as phenyl, naphthyl, tetrahydronaphthyl, indanyl, fluorenyl and the like, but preferably phenyl or naphthyl.
Optionally substituted aryl in the general formula represents preferably optionally substituted phenyl or naphthyl, in particular phenyl.
Optionally substituted arylalkyl in the general formulae represents preferably arylalkyl which is optionally substituted in the aryl moiety and/or alkyl and has 3U preferably 6 or 10, in particular 6, carbon atoms in the aryl moiety (preferably phenyl or naphthyl, in particular phenyl) arid preferably 1 to 4, in particular 1 or 2, carbon Le A 33 687-Foreign Countries atoms in the alkyl moiety, where the alkyl moiety may be straight-chain or branched.
By way of example and by way of preference, optionally substituted benzyl and phenylethyl may be mentioned.
The optionally substituted radicals of the general formulae may carry one or more, preferably 1 to 3, in particular 1 to 2, identical or different substituents.
Substituents which may be mentioned by way of example and by way of preference are:
Alkyl having preferably 1 to 4, in particular 1 to 2, carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl;
alkoxy having preferably 1 to 4, in particular 1 to 2, carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy;
alkylthio, such as methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio; halogenoalkyl having preferably 1 to 5, in particular 1 to 3, halogen atoms, where the halogen atoms are identical or different and halogen atoms preferably represent fluorine, chlorine or bromine, in particular fluorine or chlorine, such as difluoromethyl, trifluoromethyl, trichloromethyl; hydroxyl, halogen, preferably fluorine, chlorine, bromine and iodine, in particular fluorine and chlorine, cyano; nitro; amino; mono- and dialkylamino having preferably 1 to 4, in particular 1 or 2; carbon atoms per alkyl group, such as methylamino, methylethylamino, dimethylamino, n-propylamino, isopropylamino, methyl-n-butylamino;
alkylcarbonyl radicals, such as methylcarbonyl; alkoxycarbonyl having preferably 2 to 4, in particular 2 to 3, carbon atoms, such as methoxycarbonyl and ethoxycarbonyl;
alkylsulfinyl having 1 to 4, in particular 1 to 2, carbon atoms;
halogenoalkylsulfinyl having 1 to 4, in particular 1 to 2, carbon atoms and 1 to 5 halogen atoms, such as trifluoromethylsulfinyl; halogenoalkylsulfonyl having 1 to 4, in particular 1 to 2, carbon atoms and 1 to S halogen atoms, such as trifluoromethylsulfonyl, perfluoro-n-butylsulfonyl, perfluoroisobutylsulfonyl; arylsulfonyl having preferably 6 or 10 aryl carbon atoms, such as phenylsulfonyl; acyl, aryl, aryloxy, which for their part may cant' one of the abovementioned Le A 33 687-Foreign Countries substituents and the formimino radical (-HC=N-O-alkyl).
The number of these substituents is not limited, it is preferably from 1 to 4 identical or different substituents. It is also possible for two identical or different substituents to be present at the same atom or at atoms of cyclic amino groups.
Optionally substituted mono- or dialkylamino groups, alone or as component of a radical in the general formulae, represents straight-chain or branched alkyl having preferably 1 to 6, in particular 1 to 4, carbon atoms. Examples of substituted mono-or dialkylamino groups which may be mentioned are methylamino, ethylamino, dimethylamino, diethylamino, di-n-propylamino, diisopropylamino or dibutylamino.
Optionally substituted mono- or dialkoxyalkylamino groups, alone or as component of a radical in the general formulae, represents straight-chain or branched alkoxyalkyl having preferably I to 6, in particular 1 to 4, carbon atoms. Examples of substituted mono- or dialkoxyalkyl-amino groups which may be mentioned are methoxy-methylamino, methoxyethylamino, di-(methoxymethyl)-amino or di-(methoxyethyl)-amino.
Suitable cyclic amino groups are heteroaromatic or aliphatic ring systems having one or more nitrogen atoms as heteroatom, where the heterocycles may be saturated or unsaturated, be one ring system or a plurality of fused ring systems and may optionally contain further heteroatoms, such as, for example, one or two nitrogens, oxygen and sulfur, etc. Moreover, cyclic amino groups may also represent a spiro ring or a bridged ring system. The number of atoms which form the cyclic amino groups is not limited, in the case of a one ring system, for example, the groups consist of 3 to 8 atoms and in the case of a three-ring system, of 7 to 11 atoms.
Examples of cyclic amino groups having saturated and unsaturated monocyclic groups having a nitrogen atom as heteroatom which may be mentioned are 1 azetidinyl, pyrrolidino, 2-pyrrolin-I-yl, 1-pyrrolyl, piperidino, 1,4-dihydropyrazin-I
yl, 1,2,5,6-tetrahydropyrazin-1-yl, 1,4-dihydropyridin-I-yl, 1,2,5,6-tetrahydropyridin-Le A 33 6$7-Foreign Countries 1-yl, homopiperidinyl; examples of cyclic amino groups having saturated and unsaturated monocyclic groups having two or more nitrogen atoms as heteroatoms which may be mentioned are 1-imidazolidinyl, 1-imidazolyl, 1-pyrazolyl, 1-triazolyl, 1-tetrazolyl, 1-piperazinyl, 1-homopiperazinyl, 1,2-dihydro-pyridazin-1-yl, 1,2-di-hydro-pyrimidin-1-yl, perhydropyrimidin-1-yl, 1,4-diazacyclo-heptan-1-yl;
examples of cyclic amino groups having saturated and unsaturated monocyclic groups having one or two oxygen atoms and one to 3 nitrogen atoms as heteroatoms, such as, for example, oxazolidin-3-yl, 2,3-dihydroisoxazol-2-yl, isoxazol-2-yl, 1,2,3-oxadiazin-2-yl, morpholino, examples of cyclic amino groups having saturated and unsaturated monocyclic groups having one to three nitrogen atoms and one to two sulfur atoms as heteroatoms which may be mentioned are thiazolidin-3-yl, isothiazolin-2-yl, thiomorpholino, or dioxothiomorpholino; examples of cyclic amino groups having saturated and unsaturated fused cyclic groups which may be mentioned are indol-y1, 1,2-dihydrobenzimidazol-1-yl, perhydropyrrolo[1,2-a]pyrazin-2-yl; examples of cyclic amino groups having spirocyclic groups which may be mentioned are 2-azaspiro[4,5]decan-2-yl; examples of cyclic amino groups having bridged heterocyclic groups which may be mentioned are 2-azabicyclo[2,2,1 ]heptan-7-yl.
Suitable monovalent amino protective groups are acyl groups having preferably 1 to 6, in 'particular 1 to 4, carbon atoms, such as, for example, formyl, acetyl, propionyl, pivaloyl, hexanoyl or mono- (or di- or tri-) halogen-containing acyl groups, such as, for example, 2-chloro-, 2-bromo-, 2-iodo-, 2,2-dichloroacetyl, 2,2,2-trifluoroacetyl or 2,2,2-trichloroacetyl, alkoxycarbonyl groups having preferably 1 to 14, in particular 1 to 4, carbon atoms, such as, for example, rnethoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, tert-butoxycarbonyl (Boc), tert-amyloxycarbonyl {Aoc), hexyloxy-carbonyl, methylsulfonylethoxycarbonyl, adamantyloxycarbonyl (Adoc) and 1-[1-adamantyl]-1-methylethoxycarbonyl (Adpoc), carbamoyl groups, amyl groups, such as, for example phenylacetyl and phenylpropionyl, aryloxycarbonyl groups, such as, for example, phenoxycarbonyl and naphthyloxycarbonyl, aryloxyalkanoyl groups, such as, for example, phenoxyacetyl, and phenoxypropionyl, arylglyoxyloyl groups, such as, for example, phenylglyoxyloyl and naphthylglyoxyloyl, alkoxycarbonyl Le A 33 687-Foreign Countries groups having customary substituents, such as, for example, benzyloxycarbonyl (Cbo- or Cbz, Z), 4-methoxybenzyloxycarbonyl, 3,5-dimethoxybenzyloxycarbonyl, 4-phenylazobenzyl-oxycarbonyl, phenethyloxycarbonyl, nitro-benzyloxycarbonyl, chloro-benzyloxycar-bonyl, a,a-dimethyl-3,5-dimethoxy-benzyloxycarbonyl, 2-nitro-4,5-dimethoxy-benzyl-oxycarbonyl (Nvoc), fluorenyl-9-methoxycarbonyl (Fmoc), substituted or unsubstituted alkylidene groups, such as, for example, benzylidene, hydroxybenzylidene, mono- (or di- or tri-) phenylalkyl-containing alkyl groups, such as, for example, benzyl, phenethyl, benzhydryl or triphenylmethyl (trityl) and the like. Suitable bivalent amino protective groups which may be are mono- or disubstituted methylidene groups, such as 1-lower-alkoxy (for example methoxy or ethoxy)-lower alky-lidene (for example ethylidene or 1-n-butylidene), for example =C(CH3)(O-CZHS), furthermore, for example, =C(CH3)2 or =CH-phenyl, and in particular bisacyl radicals, for example the phthalyl radical, which together with the nitrogen atom to be protected forms a 1H-isoindole-1,3(2H)-dione (phthalimide group).
Amino protective group and their introduction and removal are known per se and described, for example, in J. F. W. McOmie, "Protective Groups in Organic Chemistry", Plenum Press, London, New York, 1973, and T. W. Greene, "Protective Groups in Organic Synthesis", Wiley, New York, 1984.
Suitable hydroxyl protective groups are optionally substituted alkyl groups having preferably 1 to 6, in particular 1 to 4, carbon atoms, such as, for example, tent-butyl, methylthiomethyl and trimethylsilyl, phenylalkyl-containing alkyl groups, such as, for example, benzyl or diphenylmethyl, heterocyclic groups, such as tetrahydropyranyl and the like.
Suitable thiol protective groups are optionally substituted alkyl groups having preferably 1 to 6, in particular 1 to 4, carbon atoms, such as, for example, acetamidomethyl and chloroacetamidomethyl, arylalkyl-containing alkyl groups, such as, for example, benzyl, 4-methoxybenzyl, diphenylmethyl, triphenylmethyl and pyridyldiphenylmethyl and the like.

Le A 33 687-Foreign Countries The protective groups mentioned further above have the function, known in peptide chemistry, to protect amino hydroxyl or thiol groups of compounds temporarily.
Suitable synthetic resin for use as polymeric carriers for the solid-phase synthesis of the cyclodepsipeptides according to the invention are appropriately functionalized basic polymers (in the most common form on a chloromethylated polystyrene), such as, for example, amino-oxy- or hydrazino-functionalized resins of the Merrifield type. Particularly suitable here is the commercially available DHP HM resin from Novabiochem which allows simple anchoring using a hydraxylamino- or hydrazino function and thus permits the cyclodepsipeptides according to the invention to be provided.
Particular preference is given to compounds of the general formula (Ia) A R~2 O
N'~C~O~R~~
R2 N ' ~N' O
~R~ Rio O O

R4 R~
O N~ \N R8 (Ia) .... R ~ O ~O

in which R~, R4, R' and R~° represent methyl, RZ, R5, Rg and R1l represent isobutyl, R6 and R~Z represent methyl, R3 and R9 independently of one another represent optionally substituted benzyl, substituents that may be mentioned being hydrogen, halogen, in particular Le A 33 687-Foreign Countries bromine, fluorine, chlorine or iodine, cyano, carbamoyl, hydroxyl which carries a protective group or unprotected hydroxyl, Ci.B-alkoxy, in particular methoxy, tert-butyloxy, C~.~-alkoxy-C1~-alkoxy, in particular methoxy-methoxy, 2-methoxyethoxy, Cz~-alkenyloxy, in particular allyloxy, hetaryl-C,.~-alkoxy, in particular fur-2-yl-methoxy, tetrahydrofur-2-yl-methoxy, N
Boc-pyrrolidin-2-yl-methoxy, pyrrolidin-2-yl-methoxy, 5-sec-butyl-1,2,4 oxadiazol-3-yl-methoxy, S-cyclopropyl-1,2,4-oxadiazol-3-yl-methoxy, imi dazol-5-yl-methoxy, thiazolylmethoxy, tetrazol-5-yl-methoxy, thienyl methoxy, nitro, or a radical from the group consisting of -O-CHz-CHz I O NRz3R24, -CHz-NRz3Rza~ -NRz3Rza and -SOz-NRz3Rza~
Rz3 and Rz4 independently of one another each represent hydrogen, C,~-alkyl, in particular methyl, ethyl, hetaryl-C1.~-alkyl, in particular fur-2-yl-methyl, tetrahydrofur-2-yl-methyl, pyrrolidin-2-yl-, Rz3 and Rz4 together with the nitrogen atom to which they are attached represent hetaryl, in particular N-pyrrolidino, N-piperazino, N-morpholino, N-thiomorpholino, N-piperidino, N-imidazolo, 2-oxo-pyrrolidino, phthalimino or tetrahydrophthalimino, A represents hydrogen, cyano or optionally represents a radical Al -Y-Ri3 Ai) in which Y represents oxygen or -N-R14, where R13 and R'4 independently of one another represent hydrogen, straight-chain or branched C »-alkyl, in particular methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl, tert-butyl, C~-C4-alkylcarbonyl, in particular methylcarbonyl, ethylcarbonyl, cyano-C ~ -C4-alkyl, amino-C 1-C4-Le A 33 b87-Foreign Countries alkyl, hydroxy-C~-C4-alkyl, C,~-alkylsulfonyl, in particular methylsulfonyl, C~_2-halogenoalkoxy-C~_2-alkylsulfonyl, in particular 1,1,1-trifluoroethoxyethylsulfonyl, straight-chain or branched C,~-alkyloxy-carbonyl, in particular methoxycarbonyl, ethyloxycarbonyl, propyloxycarbonyl, isopropyloxycarbonyl, isobutyloxycarbonyl, sec-butyloxycarbonyl, tert-butyl-oxycarbonyl, straight-chain or branched C1~-alkylaminocarbonyl, in particular methylaminocarbonyl, ethyl-aminocarbonyl, C2.~-alkenyl, in particular vinyl, 2-propenyl, 2-butenyl, C2.~-alkenyloxycarbonyl, in particular vinyloxycarbonvl, 2-propenyloxycarbonyl, 2-butenyloxycarbonyl, C2~-halogenoalkenyl-oxycarbonyl, in particular 1,1,2-trifluorobut-1-en-4-yl-oxycarbonyl, C2.~-alkenylaminocarbonyl, in particular 2-propenylaminocarbonyl, C2~-alkinyl, in particular 2-propinyl, C2.~-alkinyloxycarbonyl, in particular 2-propinyloxycarbonyl, cyanomethyl, hydroxyethyl, amino-ethyl, aryl-C ,_2-alkyl, in particular optionally substituted benzyl, hetaryl-C ,_2-alkyl, in particular optionally substituted hetarylmethyl, in particular optionally substituted tetrahydrofurylmethyl, furylmethyl, thienylmethyl, thiadiazolylmethyl, tetrazolylmethyl, pyridylmethyl, aryloxy-C,_2-alkyl, in particular optionally substituted phenoxyethyl, = optionally substituted hetarylcarbonyl, substituents that may be mentioned being hydrogen, nitro, amino, halogen, in particular bromine, chlorine or fluorine, C~~,-alkyl, in particular methyl, C»-halogenalkyl, in particular trifluoromethyl, phenyl, C1~-alkoxy, in particular methoxy, C ~.~-alkoxycarbonyl, in particular methoxycarbonyl, N-morpholinyl, or hetarylcarbonylmethyl, in particular N-morpholinocarbonylmethyl, N-pyrrolidinocarbonyl-methyl, or optionally represent a radical of group B4, Le A 33 687-Foreign Countries R2, O
I
QwG~Ni I ) R,s Rio (B4) Z
in which Z
ii ,G~
G represents a selectively removable protective group, for example acetyl (Ac), allyloxycarbonyl (Alloc), benzyloxycarbonyl (Z) or tert-butyloxycarbonyl (Boc), R19 represents hydrogen, RZ° represents hydrogen, propyl, isopropyl, isobutyl, benzyl, 4-hydroxybenzyl, imidazol-4-yl-methyl, indol-3-ylmethyl, phenyl, 2-hydroxyethyl, 1-hydroxyethyl, 2-methylthioethyl, 2-carbamoylethyl, . R21 represents hydrogen or C1-C4-alkyl, and their optical isomers, racemates and their physiologically acceptable salts.
Ver~particular preference is given to compounds of the general formula (Ia) Le A 33 687-Foreign Countries A R~2 O
Brit O

~R~ Rio O O

R4 R~
O N~ \N R8 (Ia) R~O~O

in which R~, R4, R~ and R'° represent methyl, S
R2, R5, R8 and R1' represent isobutyl, R6 and R12 represent methyl, R3 and R9 represent benzyl, A . represents -NHMe or a radical A' ,M..
-1'-R~3 (A

in which Y represents oxygen, R'3 represents hydrogen, straight-chain or branched C1.~-alkyl, in particular methyl, ethyl, propyl, tert-butyl, C,~-alkylsulfonyl, in particular methylsulfonyl, C~-C4-alkylcarbonyl, in particular methylcarbonyl, cyano-C~-Cg-alkyl, hydroxy-C1-C4-alkyl, Le A 33 687-Foreign Countries amino-C~-C4-alkyl, C1_Z-halogenoalkoxy-C,_2-alkylsulfonyl, in particular 1,1,1-trifluoroethoxyethylsulfonyl, straight-chain or branched C,.~-alkyloxycarbonyl, in particular methoxy-carbonyl, ethyloxycarbonyl, propyloxycarbonyl, isopropyloxy-carbonyl, isobutyloxycarbonyl, sec-butyloxycarbonyl, tert-butyloxycarbonyl, C2~-alkenyl, 2-propenyl, CZ.~-alkenyl-oxycarbonyl, in particular vinyloxycarbonyl, 2-propenyl-oxycarbonyl, C2~-halogenoalkenyloxycarbonyl, in particular 1,1,2-trifluorobut-1-en-4-yl-oxycarbonyl, C2.~-alkenylamino-carbonyl, in particular 2-propenylaminocarbonyl, C2.~-alkinyl-oxycarbonyl, in particular 2-propinyloxycarbonyl, aryl-C,_2-alkyl, in particular optionally substituted benzyl, N-morph-olinocarbonylmethyl, N-pyrrolidinocarbonylmethyl, hetaryl-C,_2-alkyl, in particular optionally substituted tetrahydio-furylmethyl, furylmethyl, 5-chloro-thiadiazol-4-yl-methyl, N-methyl-tetrazol-5-yl-methyl, pyridyl-methyl, 2-chloro-pyrid-5-yl-methyl, aryloxy-Ci_2-alkyl, in particular optionally substituted phenoxyethyl, trifluoromethylphenoxyethyl, optionally substituted hetarylcarbonyl, in particular optionally ~ substituted furylcarbonyl, pyridylcarbonyl, substituents that may be mentioned being hydrogen, nitro, amino, halogen, in particular bromine, chlorine or fluorine, methyl, trifluoro-methyl, phenyl, methoxy, methoxycarbonyl, N-morpholinyl, or optionally represents a radical from the group B4, Rz~ O
I
Q.~G~.N
II R~s Rzo in which Le A 33 687-Foreign Countries Z
n ,G~
Q represents a selectively removable protective group, for example acetyl (Ac), allyloxycarbonyl Alloc), benzyloxy-carbonyl (Z) or tert-butyloxycarbonyl (Boc), S R19 represents hydrogen, RZ° represents hydrogen, methyl, propyl, isopropyl, isobutyl, R21 represents hydrogen or methyl, and their optical isomers, racemates and their physiologically acceptable salts.
The general or preferred radical definitions or illustrations listed above can be combined with one another as desired, i.e. including combinations between the respective ranges and preferred ranges. They apply to the end product and, correspondingly, to precursors and intermediates.
The cycloiminodepsipeptides of the general formula (I) to be used according to the ""'' invention and their salts furthermore contain one or more centers of chirality, and they can therefore be present as pure stereoisomers or in the form of various enantiomer and diastereomer mixtures which, if required, can be separated in a manner known per se or else be prepared by stereoselective reactions in combination with the use of stereochemically pure starting materials.
However, preference is given to using, according to the invention, the optically active stereoisomeric forms of the compounds of the general formula (I) and their salts.
Particular preference is given to using the cyclic depsipeptides which are constructed of (S)-configured amino acids (L form) and D-configured hydroxycarboxylic acids (D form) as ring building blocks.

Le A 33 687-Forei~~n Countries Accordingly, the invention relates both to the pure enantiomers and diastereomers and to their mixtures for controlling endoparasites, in particular in the field of medicine and veterinary medicine.
Suitable salts of the cycloiminodepsipeptides of the general formula (I) which may be mentioned are customary nontoxic salts, i.e. salts with differing bases and salts with added acids. Salts with inorganic bases, such as alkali metal salts, for example sodium, potassium or cesium salts, alkaline earth metal salts, for example calcium or magnesium salts, ammonium salts, salts with organic bases and also with inorganic amines, for example triethylammonium, dicyclohexylammonium, N,N'-dibenzyl-ethylenediammonium, pyridinium, picolinium or ethanolammonium salts, salts with inorganic acids, for example hydrochlorides, hydrobromides, dihydrosulfates, trihydrosulfates, or phosphates, salts with organic carboxylic acids or sulfonic acids, for example formates, acetates, trifluoroacetates, maleates, tartrates, methane-sulfonates, benzenesulfonates or para-toluenesulfonates, salts with basic amino acids, for example arginates, aspartates or glutamates and the like may be mentioned as being preferred.
Methods for introducing optionally substituted imino functions into synthetic peptides or pharmacologically interesting heterocycles are known from the literature.
Suitable for use as starting components are here preferably the corresponding endothiopeptides or heterocyclic thiolactames. By way of example, the syntheses of amidoxime, cyanamidine and amidrazone alalogs of chemotactic peptides from endothiopeptides may be mentioned (G. Sauve et al., Can. J. Chem. 61, 1985, p. 3089). One variant for preparing the N~'-hydroxy-N~'-methyl-(R)-arginine from tert-butyl Na-tert-butoxycarbonyl-8-(N-methyl-thioureido)-(R)-norvalinate has been described by H. A. Moynihan et al. (J. Chem. Soc. Perkin Trans. I 1994, p.
769).
Likewise, it is possible to convert heterocyclic thiolactames into amidines (pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione: M. Robba et al., Tetrahedron Lett. 33 Le A 33 687-Foreign Countries (20), 1992, p. 2803) or, without any problems, azetidine-2-thiones into azetidin-2-imines (13-lactams: L. Ghosez et al., J. Chem. Soc., Chem. Commun. 1983, p.
818).
Surprisingly, it has now been found that the novel cyclic iminodepsipeptides of the S general formula (I) according to the invention can also be prepared from the corresponding cyclic thiodepsipeptides using amino compounds of the general formula (II), by reacting one or more thioamide groups. Particular preference according to the invention is given to reacting one thioamide group.
The compounds of the general formula ()7 are novel, they can be prepared, for example, by processes mentioned above under points 2 and 3.
Below, the processes according to the invention are illustrated using selected examples (cf. also Preparation Examples).
If, in the process 2a according to the invention for preparing the novel cycloiminodepsipeptides of the general formula (Ia), the compounds of the general formula (Ib) used is the cyclic thiodepsipeptide cyclo(-N-methyl-L-leucinyl-D-thiolactyl-N-methyl-L-leucinyl-D-phenyl-lactyl-N-methyl-L-leucinyl-D-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-) as amino compound of the general formula (II) the O-methyl-hydroxylamine (A: -O-Me; cf.. route A) or N-methylhydrazine (A: -NH-Me; cf. route B), the process can be represented by the reaction scheme Scheme I
below:

Le A 33 687-Foreiun Countries Scheme I
Me~~ Me Me Me Me N
Me O O
O Me N ' N ..~
Me N ' N O ~ A~ Me ~ Me Me/
Me Me/ ~~~ O
Me0 /
O O
O
Me Me\ Me B~ Me~NrH Me p Me Me O N N Me N
O O
O
Me Me N ' N ~", Me Me ~ Me Me/
MeO
syn-/anti- isomer mixtures A): HZN-O-Me ' HCI, Hg(O-Ac)Z, base B): HZN-NH-Me, Hg(O-Ac)2, base If the amino compounds of the general formula (II) are used, the compounds of the 1 U general formula (I) may be formed as a mixture of syn- and anti- isomers in the process 2a according to the invention.
The formula (Ib) provides a general definition of the cyclothiodepsipeptides required as starting materials for carrying out process 2a according to the invention.
In this formula (Ib), R' to R'2 preferably represent those radicals which have already been mentioned in connection with the description of the substances of the general formula (I) according to the invention as being preferred for these substituents.
The cyclic thiodepsipeptides used as starting materials are known from an earlier patent application and can be obtained correspondingly via thionation of cyclic depsipeptides using suitable sulfurizing agents (cf. WO 98/43965, see also Preparation Examples).

Le A 33 687-Foreign Countries The general formula (II) provides a definition of the amino compounds further to be used as starting materials for carrying out the process 2a according to the invention.
In this formula (II), A has the meaning which has already been mentioned in connection with the description of the substances of the general formula (I) according to the invention as being preferred for this substituent.
The amino compounds of the formula (II) are commercially available, some are known and can be obtained by known methods (cf., for example, hetaryl-methoxamine: US-Pat. 5 489 680; DE-OS (German Published Specification) 2119012, alkoxyamines: EP-OS 495 750; DE-OS (German Published Specification) 2206890; D. Favara et al. Farmaco, Ed. Sci. 42 ( 10), 1987, p. 697).
A general route for preparing aminoxy compounds (A = A': -Y-R'3, Y: -O-) of the 1 S formula (II) comprises, for example, reacting a hydroxylamine derivative which has a protective group on nitrogen (for example R' and R" together: phthaloyl, isopropylidene, a-hydroxy-benzylidene group) with a compound R'3-E (O-alkylation) in a diluent, followed by removal of the corresponding protective group.
In compound R'3-E, R'3 has the same meaning as above and E represents a nucleofugic leaving group, for example aliphatically or aromatically substituted sulfonyloxy, for example methanesulfonyloxy, salts of sulfonic acid, p toluenesulfonyloxy (tosyloxy), and furthermore also, for example, halogen, in particular bromine, chlorine or iodine. (cf. O-alkylation). In reaction scheme II
below, the preparation of amino compounds of the formula (II;) is shown (A =
A' : -Y
R'3, Y: -O-):

Le A 33 687-Foreign Countries Scheme 1l R' R' ~
HO-NCR" + R'3 E -.. O-N\ --.-,, R'3 p-NH2 R"
Alternatively, if a hydroxyl compound (R13-OH) is used, it is also possible to carry out, for example, an intermolecular dehydration reaction. Particularly suitable for this purpose is a variant of the Mitsunobu reaction [Synthesis 1976, p. 682] where the hydroxy compounds with N-protected hydroxylamine derivatives, such as, for example, N-hydroxyphthalimide, N-hydroxy-5-norbornene-2,3-dicarboximide or ethyl acetylhydroxamate, and, for example, triphenylphosphine and diethyl N,N'-azodicarboxylate.
The compounds of the formula (II) can expediently be released in the following manner: the hydrazinolysis can preferably be carried out in a diluent, for example alcohol, at boiling point. The hydrolysis can preferably be carried out in an aqueous, aqueous-alcoholic or alcoholic solution, by heating for a number of hours. If R' and "~ R" together represent an isopropylidene group, it is possible to use acid hydrolysis and, if R' and R" together represent an a-hydroxy-benzylidene group or R"
represents a carbethoxy group, it is possible to use both alkaline and acidic hydrolysis (cf. DE-OS (German Published Specification) 2119012; D. Favara et al. Farmaco, Ed. Sci. 42 ( 10), ( 1987) p. 697).
For preparing the salts, it is preferred to use inorganic acids, such as hydrochloric acid or sulfuric acid, in ethanolic or isopropanolic solution.
The reaction of the thiodepsipeptide of the general formula (Ib) with the amino compounds of the general formula (II) is preferably carried out in the presence of a Le A 33 687-Foreign Countries metal salt or metal oxide and; if appropriate, in the presence of a basic reaction auxiliary, using diluents.
Suitable metal salts or metal oxides for carrying out the process according to the invention are all metal salts with elements of the I. and II. transition group of the Periodic Table of the Elements. Examples which may be mentioned are the acetates, chlorides, bromides, iodides, fluorides, nitrates, sulfates, carbonates, trifluoroborates, trifluoromethanesulfonates of copper, silver, gold, zinc, cadmium or mercury.
However, preference is given to using the carbonates, trifluoroborates and trifluoromethansulfonates of the metals of the I. transition group, in particular silver, and the acetates, oxides and the halides of the metals of the II. transition group, in particular mercury.
Suitable for use as basic reaction auxiliaries for carrying out the process 2a according to the invention are all suitable acid binders, such as amines, in particular tertiary amines, and alkali metal and alkaline earth metal compounds.
Examples which may be mentioned are the hydroxides, oxides and carbonates of lithium, sodium, potassium, magnesium, calcium and barium, furthermore further basic compounds such as amidine bases or guanidine bases, such as 7-methyl-1,5,7-triazabi-cyclo(4.4.0)dec-S-ene (MTBD); diazabicyclo(4.3.0)nonene (DBN), diazabicyclo(2.2.2)-octane (DABCO), 1,8-diaza-bicyclo(5.4.0)undecene (DBU), cyclohexyl-tetrabutylgua-nidine (CyTBG), cyclohexyltetramethylguanidine (CyTMG), N,N,N,N-tetramethyl-1,8-naphthalenediamine, pentamethylpiperidine, tertiary amines, such as triethylamine, trimethylamine, tribenzylainine, triisopropylamine, tributylamine, tribenzylamine, tricyclohexylamine, triamylamine, trihexylamine, N,N-dimethyl-aniline, N,N-dimethyl-toluidine, N,N-dimethyl-p-aminopyridine, N-methyl-pyrrolidine, N-methyl-piperidine, N-methyl-imidazole, N-methyl-pyrrole, N-methyl-morpholine, N-methyl-hexamethylenimine, pyridine, 4-pyrrolidinopyridine, 4-dimethylamino-pyridine, quinoline, a-picoline, (3-picoline, Le A 33 687-Foreign Countries isoquinoline, pyrimidine, acridine, N,N,N',N'-tetramethylenediamine, N,N',N'-tetraethylenediamine, quinoxaline, N-propyl-diisopropylamine, N-ethyl-diisopropylamine, N,N'-dimethylcyclohexylamine, 2,6-lutidine, 2,4-lutidine or triethylendiamine.
Preference is given to using tertiary amines, in particular trialkylamines such as triethylamine, N,N-diisopropylethylamine, N-propyl-diisopropylamine, N,N'-dimethyl-cyclohexylarnine or N-methylmorpholine.
In general, it is advantageous to carry out the process 2a according to the invention in the presence of diluents. Diluents are preferably employed in such an amount that the reaction mixture remains readily stirrable during the entire process. Suitable diluents for carrying out the process 2a according to the invention are all inert organic solvents.
Examples which may be mentioned are: halogenated hydrocarbons, in particular chlorinated hydrocarbons, such as tetrachloroethylene, tetrachloroethane, dichloropropane, methylene chloride, dichlorobutane, chloroform, carbon tetrachloride, trichloroethane, trichloro-ethylene, pentachloroethane, difluorobenzene, 1,2=dichloroethane, chlorobenzene, bromobenzene, dichlorobenzene, chlorotoluene, "~"" trichlorobenzene; alcohols such as methanol, ethanol, isopropanol, butanol; ethers such as ethyl propyl ether, methyl tert-butyl ether, n-butyl ether, anisole, phenetole, cyclohexyl methyl ether, dimethyl ether, diethyl ether, dipropyl ether, diisopropyl ether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane, dichlorodiethyl ether and polyethers of ethylene oxide and/or propylene oxide: amines such as trimethyl-, triethyl-, tripropyl-, tributylamine, N-methylmorpholine, pyridine and tetramethylenediamine, nitrohydrocarbons such as niromethane, nitroethane, nitropropane, nitrobenzene, chloronitrobenzene, o-nitrotoluenes; nitrites such as acetonitrile, propionitrile, butyronitrile, isobutyronitrile, benzonitrile, rn-chlorobenzonitrile and also compounds such as tetrahydrothiophene dioxide and dimethyl sulfoxide, tetramethylene Le A 33 687-Foreign Countries sulfoxide, dipropyl sulfoxide, benzyl methyl sulfoxide, diisobutyl sulfoxide, dibutyl sulfoxide, diisoamyl sulfoxide; sulfones, such as dimethyl, diethyl, dipropyl, dibutyl, diphenyl, dihexyl, methyl ethyl, ethyl propyl, ethyl isobutyl and pentamethylene sulfone; aliphatic, cycloaliphatic or aromatic hydrocarbons such as pentane, hexane, heptane, octane, nonane and industrial hydrocarbons, for example white spirits with components having boiling points in the range of, for example, from 40°C to 250°C, cymene, benzine fractions within a boiling point range of from 70°C to 190°C, cyclohexane, methylcyclohexane, petroleum ether, ligroine, octane, benzene, toluene, chlorobenzene, bromobenzene, nitrobenzene, xylene; esters such as methyl, ethyl, ''°°'' 10 butyl, isobutyl acetate, and also dimethyl, dibutyl, ethylene carbonate; amides such as hexamethylenephosphoric triamide, formamide, N-methyl-formamide, N,N-dimethylformamide, N,N-dipropylformamide, N,N-dibutylformamide, N-methyl-pyrrolidine, N-methyl-caprolactam, 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidine, octylpyrrolidone, octylcaprolactam, 1,3-dimethyl-2-imidazolinedione, N-formyl-piperidine, N,N'-1,4-diformylpiperazine; ketones such as acetone, acetophenone, methyl ethyl ketone, methyl butyl ketone.
It is, of course, also possible to use mixtures of the solvents and diluents mentioned for the process according to the invention.
"~ However, preferred diluents for carrying out the process according to the invention are nitriles such as acetonitrile, propionitrile, butyronitrile, isobutyronitrile, benzonitrile or m-chlorobenzonitrile, in particular acetonitrile, propionitrile or butyronitrile, ethers such as ethyl propyl ether, methyl tert-butyl ether, n-butyl ether, cyclohexyl methyl ether, dimethyl ether, diethyl ether, dipropyl ether, diisopropyl ether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, ethylene glycol dimethyl ether, tetrahydrofuran or dioxane, in particular tetrahydrofuran or dioxane, halogenated hydrocarbons, in particular chlorinated hydrocarbons, such as tetrachloroethylene, tetrachloroethane, dichloropropane, methylene chloride, dichlorobutane, chloroform, carbon tetrachloride, trichloroethane, trichloroethylene Le A 33 687-Forei;en Countries , or pentachloroethane, in particular methylene chloride, chloroform or carbon tetrachloride.
The reaction of amino compounds of the general formula (II) according to process 2a S is carried out by reacting the cyclothiodepsipeptides of the general formula (Ib) in the presence of an amino compound of the general formula (II), in the presence of one of metal salts or metal oxides mentioned with elements of the I. and II.
transition group of the Periodic Table of the Elements and, if appropriate, in the presence of one of the basic reaction auxiliaries mentioned in one of the mentioned diluents.
The reaction time is from 10 minutes from 48 hours. The reaction is carned out at temperatures between -10°C and +200°C, preferably between +10°C and +180°C, particularly preferably at room temperature. In principle, the reaction can be carried out under atmospheric pressure. It is preferably carned out under atmospheric 1 S pressure or at pressures of up to 1 S bar and, if appropriate, under an atmosphere of protective gas (nitrogen or helium).
For carrying out the process 2a according to the invention, in general from O.S to 7.0 mol, preferably from 1.0 to S.0 mol, particularly preferably from 2.0 to 3.0 mol, of amino compound of the general formula (II) are employed per thioamide group present in the cyclothiodepsipeptides of the general formulae (Ib).
Furthermore, for carrying out the process 2a according to the invention, in general from O.S to 6.0 mol, preferably from 1.0 to 4.0 mol, particularly preferably from 1.S
2S to 2.S mol, of metal salt or metal oxide are employed per thioamide group present in the compounds of the general formulae (Ib).
After the reaction has ended, the entire reaction mixture is separated from the metal sulfide which precipitates out and, if appropriate, washed. The resulting products can be purified in a customary manner by recrystallization, distillation under reduced pressure or column chromatography (cf. also the preparation examples).

Le A 33 687-Foreign Countries If, in the processes 2b and 2c according to the invention for preparing the novel cycloiminodepsipeptides of the general formula (Ia), the compounds of the formula (Ic) used is, for example, the cyclic iminodepsipeptide cyclo[-N-methyl-L-leuci-nyl-D-(hydroxy-imino)-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-N-methyl-L-leucinyl-D-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-) and the compounds of the general formula (III) used is vinyl chloroformate (cf. route C) and the compounds of the general formula (IV) used is acetic anhydride (cf. route D), the processes can be represented by reaction scheme III below.
"~' 10 Scheme III
~ Me Me ~O~$ Me O
H Me O
M M N O
N O Me N' N
Me Me N ~ Me N 0 ~ 0~ MeO Me MeO Me O O
O
Me Me ~ Me ~ ~ M D~ Me" Me p Me O N N Me O O O
Me Me N ' N .,~
Me Me Me Met MeQ
..
syn-/anti- isomer mixtures C): Cl-CO-O-CH=CH2, base D): (CH3-CO)20 The formula (Ic) provides a general definition of the cycloiminodepsipeptides required as starting materials in particular for carrying out the processes 2b and 2c according to the invention and their salts.

Le A 33 687-Foreign Countries In this formula (Ic), Y and R~ to R12 preferably represent those radicals which have already been mentioned in connection with the description of the substances of the general formula (I) according to the invention as being preferred for these substituents.
The cycloiminodepsipeptides of the general formula {Ic) (Y: -O-) used as starting materials are novel and can be obtained either by the process 2a described further above or by the process 3 described further below.
°"""~ 10 According to process 2a, the cycloiminodepsipeptides of the general formula (Ic) (Y:
-OH) can be prepared from the cyclothiodepsipeptides of the general formula (Ib) and hydroxylamine as compound of the general formula (II) (cf. Scheme IV).
Scheme IV
Me Me O Me ~H Me p Me Me O N~ O
Me N \ Me N O ~ Me N N O
Me MeO I / HONHZ Me , Me Me /
--O O O O
Me Me O Me ~ ~ Me Me\ O Me O N \N Me O O O~ Me Y'O
,,~~'' 0 Me Me Me MeMeO Me The formulae (III) and (N) provide general definitions of the compounds furthermore to be used as starting materials for carrying out the processes 2b and 2c according to the invention.
Z
G
In the formulae (III) and (IV), ~ ~ , W, Q and Y have the meaning which have already been mentioned for these substituents in connection with the description of the substances of the general formula (I) according to the invention.

Le A 33 687-Foreign Countries The compounds of the formula (III) are generally known compounds of organic chemistry, and/or some of them can be obtained commercially or by methods known from the literature (for example Houben Weyl, Methoden der organischen Chemie [Methods of Organic Chemistry], Volume E 4).
The reaction of the cycloiminodepsipeptides (Ic) with compounds of the general formula (III) is preferably carried out in the presence of basic reaction auxiliaries using diluents.
Suitable for use as basic reaction auxiliaries for carrying out the process 2b according to the invention are all acid binders mentioned under process 2a, such as amines, in particular tertiary amines.
In process 2b, preference is given to using the tertiary amines, in particular trialkylamines such as triethylamine, N,N-diisopropylethylamine, n-propyldiisopropylamine, N,N'-dimethylcyclohexylamine or N-methylmorpholine, and also pyridine derivatives, in particular pyridine.
In the process 2b according to the invention it is, of course, also possible to use mixtures of the acid binders mentioned.
.
Suitable diluents for carrying out the process 2b according to the invention are the inert aprotic solvents mentioned under process 2a, such as, for example, dioxane, acetonitrile or tetrahydrofuran, but also halogenated hydrocarbons, in particular chlorinated hydrocarbons, such as methylene chloride or chloroform.
The process 2b is carned out by reacting compounds of the general formula (Ic) in the presence of basic reaction auxiliaries with compounds of the general formula (III), if appropriate in one of the diluents mentioned.

Le A 33 687-Foreignn Countries Alternatively and preferably, process 2b can also be carried out directly in a suitable basic reaction auxiliary without a diluent.
The formula (IV) provides a general definition of the carboxylic anhydrides to be used as starting materials for carrying out the process 2c according to the invention.
The reaction time is from 4 to 72 hours. The reaction is carried out at temperatures between -10°C and +150°C, preferably between -5°C and +80°C, particularly preferably at from 0°C to room temperature. The reaction is carned out under atmospheric pressure.
For carrying out the process 2b according to the invention, in general from 2.0 to 8.0 mol, preferably from 2.0 to 4.0 mol, of acetylating agent are employed per mole of compound of the formula (Ic).
For carrying out the process 2c according to the invention, in general from 1.0 to 3.0 mol, preferably from 1.0 to 1.5 mol, of carboxylic anhydride are employed per mole of compound of the formula (Ic).
Alternatively, process 2c can also be carned out using excess carboxylic anhydride of the formula (IV) without a diluent, as long as the reaction mixture remains readily stirrable.
After the reaction has ended, the reaction solution is washed and the organic phase is separated off, dried and concentrated under reduced pressure. The resulting products can be purified in a customary manner by recrystallization, distillation under reduced pressure or column chromatography (cf. also the Preparation Examples).
If in the process 2d a) and (3) according to the invention for preparing the novel cycloiminodepsipeptides of the general formula (Ia) the compounds of the formula (Ic) used is, for example, the cyclic iminodepsipeptide cyclo[-N-methyl-L-leuci-nyl-Le A 33 687-Foreign Countries D-(hydroxy-imino)-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-N-methyl-L-leucinyl-D-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-) the compounds of the general formula (V) used is (S)-N-tert-butyloxycarbonyl-N-methylalanine ((S)-Boc-MeAla-OH; cf.
route E) and the compounds of the general formula (VI) used is allyl isocyanate (cf.
route F), the processes can be represented by reaction scheme V below.
Scheme V
Me Me~O N~ Me Me '~' ~h Me O
Me Me Me ~ Me N w ~H Me O O
N O Me N ' N
Me Me N ' N O ~ E~ Me ~ Me Me~
Me Me/ ~~~ O
O O
Me Me O Me F7 \ Me Me / / ~ ~ ~'~"N Me O
O N N Me t O H N~
O O
Me Me N ' N .,., Me Me ~ Me Me/
MeO
syn-/anti- isomer mixtures E): (~)-Boc-MeAla-OH, BOP, base F): O=C=N-CHZ-CH=CH2, base The formula (Ic) provides a general definition of the cycloiminodepsipeptides 1 S required as starting materials for carrying out the process 2d a) and (3) according to the invention.
In these formulae (Ic), Y and R' to R'2 preferably represent those radicals which have already been mentioned in connection with the description of the substances of the general formula (I) according to the invention as being preferred for these substituents.

Le A 33 687-Foreign Countries The formula (V) provides a general definition of the compounds to be used as starting materials in particular for carrying out the process 2d a) according to the invention.
Z
G
In the formula (V), ~ ~ , Q', R16, R" and R~g have the meaning which has already been mentioned in connection with the description of the substances of the general formula (I) according to the invention for substituents.
The natural or synthetic amino acids used as starting materials can, if chiral, be present in the (S)- or (R)-form (or L- or D-form).
Examples which may be mentioned are:
Aad, Abu, yAbu, Abz, 2Abz, sAca, Acp, Adpd, Ahb, Aib, (3Aib, Ala, (3Ala, ~Ala, Alg, All, Ama, Amt, Ape, Apm, Apr, Arg, Asn, Asp, Asu, Aze, Azi, Bai, Bph, Can, Cit, Cys, {Cys)Z, Cyta, Daad, Dab, Dadd, Dap, Dapm, Dasu, Djen, Dpa, Dtc, Fel, Gln, Glu, Gly, Guv, hAla, hArg, hCys, hGln, hGlu, His, hIle, hLeu, hLys, hMet, hPhe, Pro, hSer, hThr, hTrp, hTyr, HyI, Hyp, 3Hyp, Ile, Ise, Iva, Kyn, Lant, Lcn, Leu, Lsg, Lys, (3Lys, OLys, Met, Mim, Min, nArg, Nle, Nva, Oly, Orn, Pan, Pec, Pen, Phe, Phg, Pic, Pro, OPro, Pse, Pya, Pyr, Pza, Qin, Ros, Sar, Sec, Sem, Ser, Thi, (3Thi, Thr, Thy, Thx, Tia, Tle, Tly, Trp, Trta, Tyr, Val, Nal, Tbg, Npg, Chg, Thia (cf., for example, Houben- Weyl, Methoden der Organischen Chemie, Volume XV/1 and 2, Stuttgart, 1974).
Some of the compounds of the general formula (V) can be obtained commercially or by methods known from the literature (cf., for example, N-Methylamino acids:
R. Bowmann et al., J. Chem. Soc. 1950, p. 1346; J. R. McDermott et al., Can J.
Chem. 51 (1973), p. 1915; H. Wurziger et al., Kontakte (Merck, Darmstadt) 3 (1987), p. 8).

Le A 33 687-Foreign Countries The reaction of the cycloiminodepsipeptides of the general formula (Ic) with amino acid derivatives of the formula (V) is preferably carried out in the presence of coupling agents and in the presence of a basic reaction auxiliary using diluents.
Suitable coupling agents for carrying out process 2d a are all coupling agents which are suitable for forming an amide bond [cf., for example: Houben-Weyl, Methoden der organischen Chemie, Volume 15/2; Bodanszky et al., Peptide Synthesis 2nd ed.
(Wiley & Sons, New York 1976) or Gross, Meienhofer, The Peptides, Analysis Synthesis, Biology (Academic Press, New York 1979)]. Preference is given to using the following methods: activated ester method using pentachloro- (Pcp) and penta-fluorophenol (Pfp), N-hydroxysuccinimide (HOSu), N-hydroxy-5-norbornene-2,3-dicarboxamide (HONB), 1-hydroxy-benzotriazole (HOBt) or 3-hydroxy-4-oxo-3,4-dihydro-1,2,3-benzotriazine as alcohol component, coupling with carbodiimides such as dicyclohexylcarbodiimide (DCCI) according to the DCC additive process, or using n-propanephos-phonic anhydride (PPA) and the mixed anhydride method using pivaloyl chloride, ethyl- (EEDQ) and isobutyl chloroformate (IIDQ) or coupling with phosphonium reagents, such as benzotriazol-1-yl-oxy-tris(dimethylamino-phos-phonium) hexafluorophosphate (BOP), bis(2-oxo-3-oxazolidinyl)phosphonium acid chloride (BOP-Cl), benzotriazol-1-yl-tris-pyrrolidino-phosphonium hexafluoro-phosphate (PyBOB~), bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBroP~) or using phosphonic acid ester reagents, such as diethyl cyanophosphonate (DEPC) and diphenylphosphoryl azide (DPPA) or uronium reagents, such as 2-( 1 H-benzotriazol-1-yl)-1,1,3,3-tetra-methyluronium tetrafluoro-borate (TBTU), 2-(5-nor-bornene-2,3-dicarbox-amido)-1,1,3,3-tetramethyluronium tetrafluoroborate (TNTU), 2-(2-oxo-1(2H)-pyridyl-1,1,3,3-bis-pentamethylene-tetramethyluronium tetrafluoro-borate (TSTU) or such as 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU).
Coupling with phosphonium reagents such as bis(2-oxo-3-oxazoli-dinyl)-phosphonium acid chloride (BOP-Cl), benzotriazol-1-yl-oxy-tris(dimethylamino-phosphonium) hexafluorophosphate (BOP), benzotriazol-1-yl-tris-pyrrolidino-phos-Le A 33 687-Foreign Countries phonium hexafluorophosphate (Py BOB~), bromo-tris-pyrrolidino-phosphonium hexa-fluorophosphate (PyBroP~ and phosphonic acid ester reagents, such as diethyl cyanophosphonate (DEPC) or diphenylphosphoryl azide (DPPA) is preferred.
Suitable for use as basic reaction auxiliaries for carrying out the process 2d a) according to the invention are likewise all acid binders suitable for process 2a.
Preferably suitable are tertiary amines, in particular trialkylamines such as triethylamine, N,N-diisopropylamine, N-propyldiisopropylamine, N,N'-dimethyl cyclohexylamine or N-methylmorpholine.
Suitable for use as diluents for carrying out the process 2d a) are the solvents mentioned under process 2a such as, for example, halogenated hydrocarbons, in particular chlorinated hydrocarbons, such as methylene chloride, chloroform or 1,2 dichloroethane and mixtures of these with other solvents mentioned.
The process is generally carried out by reacting compounds of the general formula (Ic) in the presence of one of the basic reaction auxiliaries mentioned with compounds of the general formula (V) in one of the solvents mentioned.
The reaction time is from 4 to 72 hours. The reaction is carried out at temperatures between -10°C and +120°C, preferably between -5°C and +50°C, particularly preferably at from 0°C to room temperature. The reaction is carried out under atmospheric pressure.
For carrying out the process 2d according to the invention, in general from 1.0 to 3.0 mol, preferably from 1.0 to 1.5 mol, of coupling agent are employed per mole of compound of the formula (Ic).

Le A 33 687-Foreign Countries The formula (VI) or (VII) provides a general definition of the compounds to be used as starting materials in particular for carrying out the process 2d l3) according to the invention.
Z
G
In these formulae (VI) or (VII), ~ ~ , Y and R~5 have the meaning which has already been mentioned in connection with the description of the substances of the general formula (I) according to the invention as being preferred for substituents.
Some of the compounds of the general formulae (VI) or (VII) can be obtained commercially or by methods known from the literature (cf., for example, Houben-Weyl, Methoden der Organischen Chemie, Volume E 4).
The reaction of the cycloiminodepsipeptides of the general formula (Ic) with compounds of the general formulae (VI) or (VII) is preferably carried out in the presence of diluents, if appropriate in the presence of a basic reaction auxiliary.
Suitable diluents for carrying out the process 2d 13) according to the invention are the solvents mentioned under process 2a such as, for example, halogenated hydrocarbons, in particular chlorinated hydrocarbons, such as methylene chloride, r"
chloroform or 1,2-dichloroethane, nitriles such as acetonitrile, propionitrile, butyronitrile, in particular acetonitrile, ethers such as ethyl propyl ether, n-butyl ether, diethyl ether, dipropyl ether, diisopropyl ether, tetrahydrofuran or dioxane, in particular tetrahydrofuran or dioxane, aliphatic or aromatic hydrocarbons such as n hexane, n-heptane, benzene, toluene or xylenes and mixtures of these with other diluents mentioned.
The process 2d !3) can also be carried out in the presence of basic reaction auxiliaries.
Suitable as such basic reaction auxiliaries for carrying out the process 2e according to the invention are all acid binders mentioned further above, but preferably tertiary amines, in particular trialkylamines such as triethylamine, N,N-Le A 33 687-Foreign Countries diisopropylethylamine or N-methylmorpholine, and amidine bases or guanidine bases such as diazabicyclo(4.3.0)nonene (DBN), diazabicyclo(2.2.2)octane (DABCO), 1,8-diazabicyclo(5.4.0)undecene (DBU), in particular 1,8-diazabicyclo(5.4.0)undecene (DBU).
S
The process 2d 13) is generally carried out by reacting compounds of the general formula (Ic) with compounds of the general formulae (Vn or (VII), if appropriate in the presence of one of the basic reaction auxiliaries mentioned in one of the diluents mentioned.
The reaction time is from 4 to 72 hours. The reaction is earned out at temperatures between -10°C and +180°C, preferably between -5°C and +120°C, particularly preferably at from 0°C to the boiling point of the diluent used. In principle, the reaction is carried out under atmospheric pressure; however, it can also be carried out 1 S under elevated or reduced pressure. It is preferably earned out at atmospheric pressure or at pressures of up to 1 S bar.
For carrying out the process 2d f3) according to the invention, in general from 1.0 to 3.O,mol, preferably from 1.0 to 1.5 mol, of compound of the general formulae (VI) or (VII) is used per mole of compound of the formula (Ic).
The invention furthermore relates to novel processes for preparing cycloiminodepsipeptides of the general formula (Ic).
The cycloiminodepsipeptides of the general formula (Ic) (Y: -O-) can either be prepared directly according to process 2a from the thiodepsipeptides of the general formula (Ib) and hydroxylamine as compound of the general formula (II) or can be obtained according to process 3 from suitable cycloiminodepsipeptides of the general formula (Ia).

Le A 33 687-Foreign Countries If, for example, in process 3a the novel cycloiminodepsipeptide cyclo[-N-methyl-L-leucinyl-D-(benzyloxy-imino)-lactyl-N-methyl-L-leucinyl-D-phenyl-lactyl-N-methyl-L-leucinyl-D-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-) is used as compound of the general formula (Ia) (A = A1= -Y-R~3: -O-CH2-phenyl) is used for hydrogenation, the corresponding cycloiminodepsipeptide cyclo[-N-methyl-L-leucinyl-D-(hydroxy-imino)-lactyl-N-methyl-L-leucinyl-D-phenyl-lactyl-N-methyl-L-leucinyl-D-lactyl-N-methyl-L-leucinyl-D-phenyl-lactyl-) is formed (cf. Scheme VI, route G).
The formula (Ia) provides a general definition of the cycloiminodepsipeptides required as starting materials for carrying out the process 3a according to the invention. In these formulae (Ia), A, R~ to R'2 preferably represent those radicals which have already been mentioned in connection with the description of the substances of the general formula (I) according to the invention as being preferred for these substituents.
The cycloiminodepsipeptides of the general formula (Ia) can be prepared according to process 2a mentioned further above from the thiodepsipeptides of the general formula (Ib) and compounds of the general formula (II) in which A represents a radical -Y-R13 (Ai) having a selectively removable O protective group R13, for example benzyl-, benzyloxycarbonyl-. Allyl-, tert-butyloxycarbonyl-, tetrahydro-pyranylhydroxylamine.
Depending on the protective group R13, in the compounds of the general formula (Ia) this group can either be selectively removed by hydrogenolysis in the presence of a suitable hydrogenation catalyst or by acidolysis in the presence of a protic acid.
According to the invention and particularly preferred is the hydrogenolysis of cycloiminodepsipeptides of the general formula (Ia) in the presence of a hydrogenation catalyst, in the presence of a diluent and, if appropriate, in the presence of an acid reaction auxiliary (Scheme VI, route G, H, I).

Le A 33 687-Foreign Countries Scheme VI

R~~ Me Me Me O
N
O
Me N N O
G) H~~ Me p Me Me Me ~ Me Me N~ 0 O O O Me N' N., Me Me\ Me I) MeO Me Me /~
O N N Me O
'O
Me Me Me Sylt-~aYlh-lSOmer mlXtLireS
G: H2, 10% Pd(OH)-carbon, H+/Me-OH (RI3: -benzyl) H: H+ (R13: -THP) THP = tetrahydropyranyl I: Pyridine para-toluenesulfonic acid (R'3 = -THP-CH2-O-CHZ-C6H4-polymer) Suitable catalysts for carrying out the catalytic hydrogenation are all customary hydrogenation catalysts, such as, for example, platinum catalysts (platinum foil, platinum sponge, platinum black, colloidal platinum, platinum oxide, platinum wire etc.), palladium catalysts (for example palladium sponge, palladium black, palladium oxide, palladium/carbon, colloidal palladium, palladium/barium sulfate, palladium/-barium carbonate, palladium hydroxide, etc.), nickel catalysts, for example reduced nickel, nickel oxide, Raney nickel etc.), ruthenium catalysts, cobalt catalysts (for example reduced cobalt, Raney cobalt etc.), iron catalysts (for example reduced iron, Raney iron etc.), copper catalysts, (for example reduced copper, Raney copper, Ullman copper etc.). However, preference is given to using noble metal catalysts, such as, for example, platinum and palladium or ruthenium catalysts, if appropriate on a suitable support, such as, for example, carbon or silicon.

Le A 33 687-Foreign Countries For hydrogenating cycloiminodepsipeptides of the general formula (Ia), the inert organic solvents mentioned under process 2a, such as, for example, alcohols, in particular methanol or ethanol, are used.
Acid reaction auxiliaries which may be mentioned are, for example, mineral acids.
The mineral acids preferably include hydrohalic acids such as hydrofluoric acid, hydrobromic acid, hydrochloric acid or hydroiodic acid, and also sulfuric acid, phosphoric acid, phosphorous acid and nitric acid.
According to the invention, for carrying out the hydrogenation, an alcoholic solution of the cyclic benzyloxyiminodepsipeptides of the formula (Ia) is reacted in the presence of a suitable hydrogenation catalyst and, if appropriate, in the presence of an acid reaction auxiliary.
Preferred for use as hydrogenation catalysts are palladium catalysts, in particular palladium/ or palladium hydroxide/carbon.
Preferred for use as acid reaction auxiliary are mineral acids, in particular hydrohalic acids such as hydrochloric acid.
,~ 20 The reaction time is from 5 minutes to 20 hours. The hydrogenation is carried out at temperatures between -5°C and +100°C, preferably between 0°C and +30°C.
Alternatively, the cyclic hydroxy-iminodepsipeptides of the general formula (lc) (Y: -O-) can also be obtained from cyclic allyloxyiminodepsipeptides of the general formula (Ia) (A: -O-CHZ-CH=CHZ)by palladium(II) acetate-catalyzed cleavage in the presence of triethylammonium formate and triphenylphosphine (T. Yamada et al., Tetrahedron Lett. 28, 1987, p. 4557).
Of course, and according to the invention, the cycloiminodepsipeptides of the general formula (Ic) (Y: -O-) can also be formed by acid-catalyzed removal of a Le A 33 687-Foreign Countries tetrahydropyranyloxy radical (A: -O-THP, cf. route H) or by removal of the anchor group R13 from polymer-O-bonded cycloiminodepsipeptides of the general formula (Ia) (for example A = A' = Y-R~3 = -O- with selectively removable anchor group) (cf.
Scheme VI, route I).
S
If, for example, in process 3b for the selective removal, the polymer-bound cycloiminodepsipeptide cyclo[-N-methyl-L-leucinyl-D-(polymer-THP-oxy-imino)-lactyl-N-methyl-L-leucinyl-D-phenyl-lactyl-N-methyl-L-leucinyl-D-lactyl-N-me-thyl-L-leucinyl-D-phenyllactyl-) is used as compound of the general formula (Ia) (A
= A~ _ -Y-R13 = -O- with selectively removable anchor group), the corresponding cycloiminodepsipeptide cyclo[-N-methyl-L-leucinyl-D-(hydroxy-imino)-lactyl-N-methyl-L-leu-cinyl-D-phenyl-lactyl-N-methyl-L-leucinyl-D-lactyl-N-methyl-L-leucinyl-D-phenyl-lactyl-) is formed (cf. Scheme VI, route I).
The formula (Ia) provides a general definition of the cycloiminodepsipeptides required as starting materials for carrying out the process 3b according to the invention.
In these formulae (Ia), A and R' to R'2 preferably represent those radicals which have already been mentioned in connection with the description of the substances of the general formula (I) according to the invention for these substituents.
The polymer-bound cycloiminodepsipeptides of the general formula (Ia) can be prepared according to process 2a mentioned further above from the 2~ cyclothiodepsipeptides of the general formula (1b) and polymeric supports with selectively removable anchor group for A = -Y-R'3 (A') of the general formula (II) (cf. Schema VII).

Le A 33 687-Foreign Countries Scheme VII
Me Me P Me f S~O
\ O O O~NHz Me N' N."~ ---MeO Me Me P
\ Ow,,/CO~,~ Me O Me NN O
Me N ' N .."~
MeO Me Me Some of the polymeric Garners used as starting materials and having selectively removable anchor group for A = -Y-R'3 (A1) of the general formula (I>7 are known from the literature (cf., for example, Syntheses of Hydroxamic acids:
Mitsunobu reaction on Wang resin using N-hydroxyphthalimide: D. Floyd et al. Tetrahedron Lett. 37 (44), 1996, p.8045; Reaction of trityl chloride resin with N-hydroxyphthalimide: U. Bauer et al. Tetrahedron Lett. 38 (41), 1997, p. 7233), or they can be obtained by methods known from the literature (cf. Synthesis of ketones:
Reactions with DHP HM resin: O. B. Wallace Tetrahedron Lett. 38 (28), 1997, s.
p. 4939; Alcohol coupling: J. A. Ellmann et al. J. Org. Chem. 60, 1995, p.
7712; J. A.
Ellmann et al. Tetrahedron Lett. 35 (50), p. 9333) (cf. Scheme Vl~.

Le A 33 687-Foreign Countries Scheme VIII
P
O~ DHP HM resin ~~..//1~~ J (Novabiochem) O
P O
\ I O.,~O,N
O
"~.», P
,~ I O 1~ O . NHZ
For carrying out the process 3b according to the invention, preference is given to using the 6-(aminoxy)-3,4,5,6-tetrahydro-2H-pyran-2-yl-methoxymethyl-polystyrene resin obtained according to Scheme VIII (cf. Preparation Examples).
The cyclic hydroxy-iminodepsipeptides formed in this manner are worked up in a customary manner, for example by chromatographic purification (cf. also Preparation Examples). However, they can also be reacted directly (without further purification) according to process 2b.
The iminodepsipeptides of the general formula (I) obtainable by process 2 according to the invention can be present as syn- and anti- isomers; however, under the given reaction conditions for process 2, a mixture of the two isomeric forms is preferably formed.
The "inert solvents" referred to in process variants 2 above in each case refer to solvents which are inert under the respective reaction conditions but which do not have to be inert under any reaction conditions.

Le A 33 687-Foreign Countries The active compounds are suitable for controlling pathogenic endoparasites encountered in humans and in animal husbandry and livestock breeding, in productive livestock, breeding stock, zoo animals, laboratory animals, animals used in experiments, and pets, and have low toxicity toward warm-blooded animals.
They are active against resistant and normally sensitive species and against all or some stages of development of the pests. By controlling the pathogenic endoparasites, it is intended to reduce disease, mortality and decreasing performance (for example in the production of meat, milk, wool, hides, eggs, honey, etc.), so that more economical and simpler animal husbandry is possible by using the active compounds. The pathogenic endoparasites include cestodes, trematodes and nematodes, in particular:
From the order of the Pseudophyllidea, for example Diphyllobothrium spp., Spirometra spp., Schistocephalus spp., Ligula spp., Bothridium spp., Diphlogonoorus spp.
From the order of the Cyclophyllidea, for example Mesocestoides spp., Anoplocephala spp., Paranoplocephala spp., Moniezia spp., Thysanosomsa spp., Thysaniezia spp., Avitellina spp., Stilesia spp., Cittotaenia spp., Anhyra spp., Bertiella spp., Taenia spp., Echinococcus spp., Hydratigera spp., Davainea spp., Raillietina spp., Hymenolepis spp., Echinolepis spp., Echinocotyle spp., Diorchis spp., Dipylidium spp., Joyeuxiella spp.,-Diplopylidium spp.
From the subclass of the Monogenea, for example Gyrodactylus spp., Dactylogyrus spp., Polystoma spp.
From the subclass of the Digenea, for example Diplostomum spp., Posthodiplostomum spp., Schistosoma spp., Trichobilharzia spp., Ornithobilharzia spp., Austrobilharzia spp., Gigantobilharzia spp., Leucochloridium spp., Brachylaima spp., Echinostoma spp., Echinoparyphium spp., Echinochasmus spp., Hypoderaeum spp., Fasciola spp., Fasciolides spp., Fasciolopsis spp., Cyclocoelum spp., Typhloccelum spp., Paramphistomum spp., Calicophoron spp, Cotylophoron spp., Gigantocotyle spp., Fischoederius spp., Gastrothylacus spp., Notocotylus spp., Catatropis spp., Plagiorchis Le A 33 687-Foreign Countries spp., Prosthogonismus spp., Dicrocoelium spp., Collyriclum spp., Nanophyetus spp., Opisthorchis spp., Clonorchis spp., Metorchis spp., Heterophyes spp., Metagonimus spp.
From the order of the Enoplida, for example Trichuris spp., Capillaria spp., Trichlomosoides spp., Trichinella spp.
From the order of the Rhabditida, for example Micronema spp., Strongyloides spp.
From the order of the Strongylida, for example Stronylus spp., Triodontophorus spp., Oesophagodontus spp., Trichonema spp., Gyalocephalus spp., Cylindropharynx spp., Poteriostromum spp., Cyclococercus spp., Cylicostephanus spp., Oesophagostomum spp., Chabertia spp., Stephanurus spp., Ancylostoma spp., Uncinaria spp., Bunostomum spp., Globocephalus spp., Syngamus spp., Cyathostoma spp., Metastrongylus spp., Dictyocaulus spp., Muellerius spp., Protostrongylus spp., Neostrongylus spp., Cystocaulus spp., Pneumostrongylus spp., Spicocaulus spp., Elaphostrongylus spp., Parelaphostrongylus spp., Crenosoma spp., Paracrenosoma spp., Angiostrongylus spp., Aelurostrongylus spp., Filaroides spp., Parafilaroides spp., Trichostrongylus spp., Haemonchus spp., Ostertagia spp., Marshallagia spp., Cooperia spp., ~Nematodirus spp., Hyostrongylus spp., Obeliscoides spp., Amidostomum spp., Ollulanus spp., Cyclicocyclus spp., Cylicodontophorus spp.
From the order of the Oxyurida, for example Oxyuris spp., Enterobius spp., Passalurus spp., Syphacia spp., Aspiculuris spp., Heterakis spp.
From the order of the Ascaridia, for example Ascaris spp., Toxascaris spp., Toxocara spp., Parascaris spp., Anisakis spp., Ascaridia spp.
From the order of the Spirurida, for example Gnathostoma spp., Physaloptera spp., 3U Thelazia spp., Gongylonema spp., Habronema spp., Parabronema spp., Draschia spp., Dracunculus spp.

Le A 33 687-Forei~~n Countries From the order of the Filariida, for example Stephanofilaria spp., Parafilaria spp., Setaria spp., Loa spp., Dirofilaria spp., Litomosoides spp., Brugia spp., Wuchereria spp., Onchocerca spp.
From the group of the Gigantorhynchida, for example Filicollis spp., Moniliformis spp., Macracanthorhynchus spp., Prosthenorchis spp.
- The productive livestock and breeding stock include mammals, such as, for example, cattle, horses, sheep, pigs, goats, camels, water buffalo, donkeys, rabbits, fallow deer, reindeer, fur-bearing animals, such as, for example, minks, chinchilla or raccoon, birds, such as, for example chickens, geese, turkeys or ducks, fresh and saltwater fish, such as, for example, trouts, carps, eels, reptiles, insects, such as, for example, honeybee and silkworm.

The laboratory and animals used in experiments include mice, rats, guinea pigs, golden hamsters, dogs and cats.
The pets include dogs and cats.
Administration can be effected prophylactically as well as therapeutically.
The active compounds are administered, either directly or in the form of suitable preparations, enterally, parenterally, dermally, nasally, by treating the habitat or with 2S the aid of shaped articles containing the active compound, such as, for example, strips, plates, tapes, collars, ear tags, limb bands and marking devices.
Enteral administration of the active compounds is effected for example orally in the form of powders, suppositories, tablets, capsules, pastes, drinks, granules, drenches, boluses, medicated feed or drinking water. Dermal application is effected, for example, in the form of dipping, spraying, bathing, washing, pouring-on and spotting-on and Le A 33 687-Foreign Countries _68_ powdering. Parenteral administration is effected, for example, in the form of injection (intramuscular, subcutaneous, intravenous or intraperitoneal) or by implants.
Suitable preparations include:
solutions, such as solutions for injection, oral solutions, concentrates for oral administration after dilution, solutions for use on the skin or in body cavities, pour-on formulations, gels;
emulsions and suspensions for oral or dermal administration and for injection;
semi-solid preparations;
formulations in which the active compound is incorporated in an ointment base or in an oil-in-water or water-in-oil emulsion base;
solid preparations, such as powders, premixes or concentrates, granules, pellets, tablets, boluses, capsules; aerosols and inhalants, shaped articles containing the active compound.
Solutions for injection are administered intravenously, intramuscularly and subcutaneously.
Solutions for injection are prepared by dissolving the active compound in a suitable solvent and, if desired, adding additives, such as solubilizers, acids, bases, buffer salts, antioxidants, or preservatives. The solutions are sterile-filtered and decanted into containers.
Suitable solvents include: physiologically acceptable solvents, such as water, alcohols, such as ethanol, butanol, benzyl alcohol, glycerol, hydrocarbons, propylene glycol, polyethylene glycols and N-methylpyrrolidone, and their mixtures.
If appropriate, the active compounds can also be dissolved in physiologically acceptable vegetable or synthetic oils which are suitable for injection.
Suitable solubilizers include: solvents which facilitate the dissolution of the active compound in the main solvent or which prevent precipitation of the active compound.

Le A 33 687-Forei n Countries Examples of solubilizers are polyvinylpyrrolidone, polyethoxylated castor oil and polyethoxylated sorbitan esters.
The following are preservatives: benzyl alcohol, trichlorobutanol, p-hydroxybenzoic S esters or n-butanol.
Oral solutions are administered directly. Concentrates are first diluted to the administration concentration and then administered orally. Oral solutions and concentrates are prepared as described above in the case of the solutions for injection, sterile procedures not being necessary.
Solutions for use on the skin are applied drop by drop, smoothed on, rubbed in, splashed on or sprayed on, or applied by dipping, bathing or washing. These solutions are prepared as described above in the case of the solutions for injection.
It may be advantageous to add thickeners in the preparation process.
The following are thickeners: inorganic thickeners, such as bentonites, colloidal silica, aluminium monostearate, or organic thickeners, such as cellulose derivatives, polyvinyl alcohols and their copolymers, acrylates and methacrylates.
Gels are applied to the skin or smoothed on or introduced into body cavities.
Gels are prepared by adding such an amount of thickener to solutions which have been prepared as described for the solutions for injection that a clear composition is formed which has an ointment-like consistency. The thickeners used are the thickeners indicated further above.
Pour-on and spot-on formulations are poured or splashed onto limited areas of the skin, the active compound either penetrating the skin and acting systemically or being distributed on the surface of the body.

Le A 33 687-Foreign Countries Pour-on and spot-on formulations are prepared by dissolving, suspending or emulsifying the active compound in suitable solvents or solvent mixtures which are tolerated by the skin. If appropriate, other auxiliaries, such as colorants, bioabsorption promoters, antioxidants, photostabilizers or tackifiers are added.
Suitable solvents include: water, alkanols, glycols, polyethylene glycols, polypropylene glycols, glycerol, aromatic alcohols, such as benzyl alcohol, phenylethanol or phenoxyethanol, esters, such as ethyl acetate, butyl acetate or benzyl benzoate, ethers, such as alkylene glycol alkyl ethers, such as dipropylene glycol monomethyl ether or ..
diethylene glycol monobutyl ether, ketones, such as acetone or methyl ethyl ketone, aromatic and/or aliphatic hydrocarbons, vegetable or synthetic oils, DMF, dimethylacetamide, N-methylpyrrolidone, or 2,2-dimethyl-4-oxy-methylene-1,3-dioxolane.
Colorants are all colorants which can be dissolved or suspended and which are approved for use in animals.
Examples of bioabsorption promoters are DMSO, spreading oils, such as isopropyl myristate, dipropylene glycol pelargonate, silicone oils, fatty acid esters, triglycerides or fatty alcohols.
The following are antioxidants: sulfites or metabisulfites, such as potassium metabisulfite, ascorbic acid, butylhydroxytoluene, butylhydroxyanisole or tocopherol.
Example of photostabilizers are substances from the class of the benzophenones or novantisolic acid.
Tackifiers are, for example, cellulose derivatives, starch derivatives, polyacrylates or natural polymers such as alginates or gelatin.
Emulsions can be administered orally, dermally or as injections.

Le A 33 687-Foreign Countries Emulsions are either the water-in-oil type or the oil-in-water type.
They are prepared by dissolving the active compound either in the hydrophobic or in the hydrophilic phase arid by homogenizing this phase with the solvent of the other phase, with the aid of suitable emulsifiers and, if appropriate, other auxiliaries, such as colorants, bioabsorption promoters, preservatives, antioxidants, photostabilizers, and viscosity-increasing substances.
Suitable hydrophobic phases (oils) include: paraffin oils, silicone oils, natural vegetable oils such as sesame oil, almond oil or castor oil, synthetic triglycerides, such as caprylic/capric acid biglyceride, a triglyceride mixture with vegetable fatty acid of chain length C8_,2 or other specifically selected natural fatty acids, mixtures of partial glycerides of saturated or unsaturated fatty acids which may also contain hydroxyl groups, and mono- and diglycerides of the C8/C~o-fatty acids.
Fatty acid esters, such as ethyl stearate, di-n-butyryl adipate, hexyl laurate, dipropylene glycol pelargonate, esters of a branched fatty acid having a medium chain length with saturated fatty alcohols of chain length Ci6-C18, isopropyl myristate, isopropyl palmitate, caprylic/capric esters of saturated fatty alcohols of chain length C~2-C,B, isopropyl stearate, oleyl oleate, decyl oleate, ethyl oleate, ethyl lactate, waxy fatty acid esters such as artificial duck uropygial fat, dibutyl phthalate, diisopropyl adipate, ester mixtures related to the latter, etc.
Fatty alcohols, such as isotridecyl alcohol, 2-octyldodecanol, cetylstearyl alcohol or oleyl alcohol.
Fatty acids, such as, for example, oleic acid and its mixtures.
Suitable hydrophilic phases include:
water, alcohols, such as, for example, propylene glycol, glycerol, sorbitol and their mixtures.

Le A 33 687-Foreign Countries Suitable emulsifiers include: nonionic surfactants, for example polyethoxylated castor oil, polyethoxylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate or alkylphenol polyglycol ethers;
ampholytic surfactants, such as disodium N-lauryl-(3-iminodipropionate or lecithin;
anionic surfactants, such as sodium lauryl sulfate, fatty alcohol ether sulfates, and the monoethanolamine salt of mono/dialkylpolyglycol ether orthophosphoric ester;
cationic surfactants such as cetyltrimethylammonium chloride.
Other suitable auxiliaries include: substances which increase the viscosity and stabilize the emulsion, such as carboxymethylcellulose, methylcellulose and other cellulose and starch derivatives, polyacrylates, alginates, gelatin, gum arabic, polyvinylpyrrolidone, polyvinyl alcohol, methylvinyl ether/maleic anhydride copolymers, polyethylene glycols, waxes, colloidal silica, or mixtures of the listed substances.
Suspensions can be administered orally, dermally or as an injection. They are prepared by suspending the active compound in a liquid excipient, if appropriate with the addition of other auxiliaries, such as wetting agents, colorants, bioabsorption promoters, preservatives, antioxidants, photostabilizers.
Suitable liquid excipients include all homogeneous solvents and solvent mixtures.
Suitable wetting agents (dispersants) include the surfactants indicated further above.
Other suitable auxiliaries include those indicated further above.
Semi-solid preparations can be administered orally or dermally. They are only distinguished from the above-described suspensions and emulsions by their higher viscosity.
To prepare solid preparations, the active compound is mixed with suitable excipients, if appropriate with the addition of auxiliaries, and the mixture is formulated as desired.

Le A 33 687-Foreign Countries Suitable excipients include all physiologically acceptable solid inert substances. All those are inorganic and organic substances. Inorganic substances are, for example, common salt, carbonates such as calcium carbonate, hydrogen carbonates, aluminium oxides, silicas, clays, precipitated or colloidal silica, and phosphates.
Organic substances are, for example, sugars, cellulose, foodstuffs and animal feeds, such as powdered milk, animal meals, cereal meals, coarse cereal meals and starches.
Auxiliaries are preservatives, antioxidants and colorants which have akeady been mentioned further above.
Other suitable auxiliaries are lubricants and glidants, such as, for example, magnesium stearate, stearic acid, talc, bentonites, disintegrants, such as starch or crosslinked polyvinylpyrrolidone, binders, such as, for example, starch, gelatin or linear polyvinylpyrrolidone, and dry binders, such as microcrystalline cellulose.
The active compound according to the invention can be present in its commercially available formulations and in the use forms, prepared from these formulations, as a mixture with other active compounds, such as insecticides, sterilizing agents, bactericides, acaricides, nematicides or fungicides. The insecticides include, for example, phosphoric acid esters, carbamates, carboxylates, chlorinated hydrocarbons, phenylureas, nicotinyles, neonicotinyles and substances produced by microorganisms, inter alia.
Particularly favourable examples of co-components in mixtures are the following compounds:
Fungicides:
aldimorph, ampropylfos, ampropylfos-potassium, andoprim, anilazine, azaconazole, azoxystrobin, Le A 33 687-Foreign Countries benalaxyl, benodanil, benomyl, benzamacril, benzamacril-isobutyl, bialaphos, binapacryl, biphenyl, bitertanol, blasticidin-S, bromuconazole, bupirimate, buthiobate, calcium polysulfide, capsimycin, captafol, captan, carbendazim, carboxin, carvon, S quinomethionate, chlobenthiazone, chlorfenazole, chloroneb, chloropicrin, chlorothalonil, chlozolinate, clozylacon, cufraneb, cymoxanil, cyproconazole, cyprodinil, cyprofuram, debacarb, dichlorophen, diclobutrazole, diclofluanid, diclomezine, dicloran, diethofencarb, difenoconazole, dimethirimol, dimethomorph, diniconazole, diniconazole-M, dinocap, diphenylamine, dipyrithione, ditalimfos, dithianon, dodemorph, dodine, drazoxolon, edifenphos, epoxiconazole, etaconazole, ethirimol, etridiazole, famoxadon, fenapanil, fenarimol, fenbuconazole, fenfuram, fenitropan, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone, 1 S fluazinam, flumetover, fluoromide, fluquinconazole, flurprimidol, flusilazole, flusulfamide, flutolanil, flutriafol, folpet, fosetyl-aluminium, fosetyl-sodium, fthalide, fuberidazole, furalaxyl, furametpyr, furcarbonil, furconazole, furconazole-cis, furmecyclox, guazatine, hexachlorobenzene, hexaconazole, hymexazole, imazalil, imibenconazole, iminoctadine, iminoctadine albesilate, iminoctadine triacetate, iodocarb, ipconazole, iprobenfos (IBP), iprodione, irumamycin, isoprothiolane, isovaledione, kasugamycin, kresoxim-methyl, copper preparations, such as: copper hydroxide, 2S copper naphthenate, copper oxychloride, copper sulfate, copper oxide, oxine-copper and Bordeaux mixture, mancopper, mancozeb, maneb, meferimzone, mepanipyrim, mepronil, metalaxyl, metconazole, methasulfocarb, methfuroxam, metiram, metomeclam, metsulfovax, mildiomycin, myclobutanil, myclozolin, nickel dimethyldithiocarbamate, nitrothal-isopropyl, nuarimol, ofurace, oxadixyl, oxamocarb, oxolinic acid, oxycarboxim, oxyfenthiin, Le A 33 687-Foreign Countries paclobutrazole, pefurazoate, penconazole, pencycuron, phosdiphen, pimaricin, piperalin, polyoxin, polyoxorim, probenazole, prochloraz, procymidone, propamocarb, propanosine-sodium, propiconazole, propineb, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, pyroxyfur, quinconazole, quintozene (PCNB), sulfur and sulfur preparations, tebuconazole, tecloftalam, tecnazene, tetcyclacis, tetraconazole, thiabendazole, thicyofen, thifluzamide, thiophanate-methyl, thiram, tioxymid, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazbutil, triazoxide, trichlamide, tricyclazole, 1U tridemorph, triflumizole, triforine, triticonazole, uniconazole, validamycin A, vinclozolin, viniconazole, zarilamide, zineb, ziram and also Dagger G, OK-8705, OK-8801, a-( 1,1-dimethylethyl)-J3-(2-phenoxyethyl)-1 H-1,2,4-triazole-1-ethanol, a-(2,4-dichlorophenyl)-(3-fluoro-b-propyl-1 H-1,2,4-triazole-1-ethanol, a-(2,4-dichlorophenyl)-(3-methoxy-a-methyl-1 H-1, 2,4-triazo le-1-ethanol, a-(5-methyl-1,3-dioxan-5-yl)-[3-[[4-(trifluoromethyl)-phenyl]-methylene]-1H-1,2,4-triazole-1-ethanol, (5RS,6RS)-6-hydroxy-2,2,7,7-tetramethyl-5-( 1 H-1,2,4-triazol-1-yl)-3-octanone, (E)-a-(methoxyimino)-N-methyl-2-phenoxy-phenylacetamide, isopropyl {2-methyl-1-[[[1-(4-methylphenyl)-ethyl]-amino]-carbonyl]-propyl}-carbamate, 1-(2,4-dichlorophenyl)-2-( 1 H-1,2,4-triazol-1-yl)-ethanone-O-(phenylmethyl)-oxime, 1-(2-methyl-1-naphthalenyl)-1 H-pyrrole-2, 5-dione, 1-(3,5-dichlorophenyl)-3-(2-propenyl)-2,5-pyrrolidinedione, 1-[(diiodomethyl)-sulfonyl]-4-methyl-benzene, 1-[[2-(2,4-dichlorophenyl)-1,3-dioxolan-2-yl]-methyl]-1 H-imidazole, 1-[[2-(4-chlorophenyl)-3-phenyloxiranyl]-methyl]-1 H-1,2,4-triazole, Le A 33 687-Foreign Countries 1-[ 1-[2-[(2,4-dichlorophenyl)-methoxy]-phenyl]-ethenyl]-1 H-imidazole, 1-methyl-5-nonyl-2-(phenylmethyl)-3-pyrrolidinol, 2',6'-dibromo-2-methyl-4'-trifluoromethoxy-4'-trifluoro-methyl-1,3-thiazole-5-carboxanilide, 2,2-dichloro-N-[ 1-(4-chlorophenyl)-ethyl]-1-ethyl-3-methyl-cyclopropanecarboxamide, 2,6-dichloro-5-(methylthio)-4-pyrimidinyl-thiocyanate, 2,6-dichloro-N-(4-trifluorornethylbenzyl)-benzamide, 2,6-dichloro-N-[[4-(trifluoromethyl)-phenyl]-methyl]-benzarnide, 2-(2,3,3-triiodo-2-propenyl)-2H-tetrazole, 2-[( 1-methylethyl)-sulfonyl]-5-(trichloromethyl)-1,3,4-thiadiazole, 2-[[6-deoxy-4-O-(4-O-methyl-(3-D-glycopyranosyl)-a-D-glucopyranosyl]-amino]-4-methoxy-1 H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile, 2-aminobutane, 2-bromo-2-(bromomethyl)-pentanedinitrile, 2-chloro-N-(2,3-dihydro-1,1, 3-trimethyl-1 H-inden-4-yl )-3-pyridinecarboxamide, 2-chloro-N-(2,6-dimethylphenyl)-N-(isothiocyanatomethyl)-acetamide, 2-phenylphenol (OPP), 3,4-dichloro-1-[4-(difluoromethoxy)-phenyl]-1 H-pyrrole-2,5-dione, 3,5-dichloro-N-[cyano-[(1-methyl-2-propynyl)-oxy]-methyl]-benzarnide, 3-( 1,1-dimethylpropyl)-1-oxo-1 H-indene-2-carbonitrile, 3-[2-(4-chlorophenyl)-5-ethoxy-3-isoxazolidinyl]-pyridine, 4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1 H-imidazole-1-sulfonamide, 4-methyl-tetrazolo[ 1,5-a]quinazolin-5(4H)-one, 8-(1,1-dimethylethyl)-N-ethyl-N-propyl-1,4-dioxaspiro[4.5]decane-2-methanamine, 8-hydroxyquinoline sulfate, 9H-xanthene-2-[(phenylamino)-carbonyl]-9-carboxylic hydrazide, bis-( 1-methylethyl)-3-methyl-4-[(3-methylbenzoyl)-oxy]-2,5-thiophenedicarboxylate, cis-1-(4-chlorophenyl)-2-( 1 H-1,2,4-triazol-1-yl)-cyc loheptanol, cis-4-[3-[4-(l,l-dimethylpropyl)-phenyl-2-methylpropyl]-2,6-dimethyl-morpholine hydrochloride, Le A 33 687-Forei~ Countries _77_ ethyl [{4-chlorophenyl)-azo]-cyanoacetate, potassium hydrogen carbonate, methanetetrathiol sodium salt, methyl 1-(2, 3-dihydro-2,2-di methyl-1 H-inden-1-yl)-1 H-imidazole-5-carboxylate, methyl N-(2,6-dimethylphenyl)-N-(5-isoxazolylcarbonyl)-DL. alaninate, methyl N-(chloroacetyl)-N-(2,6-dimethylphenyl)-DL-ataninate, N-{2,3-dichloro-4-hydroxyphenyl)-1-methyl-cyclohexanecarboxamide, N-(2,6-dimethylphenyl)-2-methoxy-N-(tetrahydro-2-oxo-3-furanyl)-acetamide, N-(2,6-dimethylphenyl)-2-methoxy-N-(tetrahydro-2-oxo-3-thienyl)-acetamide, N-{2-chloro-4-nitrophenyl)-4-methyl-3-nitro-benzenesulfonarnide, N-(4-cyclohexylphenyl)-1,4,5,6-tetrahydro-2-pyrimidinamine, N-(4-hexylphenyl)-1,4,5,6-tetrahydro-2-pyrimidinamine, N-(5-chloro-2-methylphenyl)-2-methoxy-N-(2-oxo-3-oxazolidinyl)-acetamide, N-(6-methoxy)-3-pyridinyl)-cyclopropanecarboxamide, N-[2,2,2-trichloro-1-[(chloroacetyl)-amino]-ethyl]-benzamide, N-[3-chloro-4,5-bis-(2-propinyloxy)-phenyl]-N'-methoxy-methanirnidamide, N-formyl-N-hydroxy-DL-alanine sodium salt, O,O-diethyl [2-(dipropylamino)-2-oxoethyl]-ethylphosphorarnidothioate, O-methyl S-phenyl phenylpropylphosphoramidothioate, S-methyll,2,3-benzothiadiazole-7-carbothioate, spiro[2H]-1-benzopyrane-2,1'(3'H)-isobenzofuran]-3'-one.
Bactericides:
bronopol, dichlorophen, nitrapyrin, nickel dimethyldithiocarbamate, kasugamycin, octhilinone, furancarboxylic acid, oxytetracyclin, probenazole, streptomycin, tecloftalam, copper sulfate and other copper preparations, quinoloes, such as ciprofloxacin, danofloxacin, difloxacin, enrofloxacin, flumequine, ibafloxacin, marbofloxacin, norfloxacin, ofloxacin, orbifloxacin, premafloxacin, sarafloxacin.

Le A 33 687-Foreign Countries _ -78-Insecticides / acaricides / nematicides:
abamectin, acephate, acetamiprid, acrinathrin, alanycarb, aldicarb, aldoxycarb, alpha-cypermethrin, alphamethrin, amitraz, avermectin, AZ 60541, azadirachtin, azamethiphos, azinphos A, azinphos M, azocyclotin, Bacillus popilliae, Bacillus sphaericus, Bacillus subtilis, Bacillus thuringiensis, Baculoviruses, Beauveria bassiana, Beauveria tenella, bendiocarb, benfuracarb, bensultap, benzoximate, betacyfluthrin, bifenazate, bifenthrin, bioethanomethrin, biopermethrin, BPMC, bromophos A, bufencarb, buprofezin, butathiofos, butocarboxim, butylpyridaben, ....
cadusafos, carbaryl, carbofuran, carbophenothion, carbosulfan, cartap, chloethocarb, chlorethoxyfos, chlorfenapyr, chlorfenvinphos, chlorfluazuron, chlormephos, chlorpyrifos, chlorpyrifos M, chlovaporthrin, cis-resmethrin, cispermethrin, clocythrin, cloethocarb, clofentezine, clothianidine, c;oumafos, cyanophos, cycloprene, cycloprothrin, cyfluthrin, cyhalothrin, cyhexatin, cypermethrin, cyromazine, cythioate, chlorothianidin, deltamethrin, demeton M, demeton S, demeton-S-methyl, diafenthiuron, diazinon, dichlorvos, dicyclanil, diflubenzuron, dimethoate, dimethylvinphos, diofenolan, disulfoton, docusat-sodium, dofenapyn, dinotefuran, eflusilanate, emamectin, empenthrin, endosulfan, eprinomectin, esfenvalerate, ethiofencarb, ethion, ethiprole, ethoprophos, etofenprox, etoxazole, etrimfos, fenamiphos, fenazaquin, fenbutatin oxide, fenitrothion, fenothiocarb, fenoxacrim, fenoxycarb, fenpropathrin, fenpyrad, fenpyrithrin, fenpyroximate, fenthion, fenvalerate, fipronil, fluazinam, fluazuron, flubrocythxinate, flucycloxuron, flucythrinate, flufenoxuron, flumethrin, flutenzine, fluvalinate, fonophos, fosmethilan, fosthiazate, fubfenprox, furathiocarb, flupyrazofos, granulosis viruses, halofenozide, HCH, heptenophos, hexaflumuron, hexythiazox, hydroprene, imidacloprid, indoxacarb, isazofos, isofenphos, isoxathion, ivermectin, nuclear polyhedrosis viruses, lambda-cyhalothrin, lufenuron, Le A 33 687-Foreign Countries malathion, mecarbam, metaldehyde, methamidophos, metharhizium anisopliae, metharhizium flavoviride, methidathion, methiocarb, methomyl, methonrene_ methoxyfenozide, metolcarb, metoxadiazone, metrifonat, mevinphos, milbemectin, rnonocrotophos, moxidectin, naled, nitenpyram, nithiazine, novaluron, NEEM, omethoate, oxamyl, oxydemethon M, Paecilomyces fumosoroseus, parathion A, parathion M, ;permethrin, phenthoate, phorate, phosalone, phosmet, phosphamidon, phoxim, pirimicarb, pirimiphos A, pirimiphos M, profenofos, promecarb, propoxur, prothiofos, prothoate, pymetrozine, pyraclofos, pyresmethrin, pyrethrum, pyridaben, pyridathion, pyrimidifen, pyriproxyfen, protrifenbute, quinalphos, ribavirin, salithion, sebufos, selamectin, silafluofen, spinosad, spiiodiclofen, sulfotep, sulprofos, S 1812, tau-fluvalinate, tebufenozide, tebufenpyrad, tebupirimiphos, teflubenzuron, tefluthrin, temephos, temivinphos, terbufos, tetrachlorvinphos, thetacypermethrin, thiamethoxam, thiapronil, thiatriphos, thiocyclam hydrogen oxalate, thiodicarb, thiofanox, thuringiensin, tralocythrin, tralomethrin, triarathene, triazamate, triazophos, triazurone, trichlophenidine, trichlorfon, triflumuron, trimethacarb, .~-..
thiacloprid, vamidothion, vaniliprole, Verticillium lecanii, YI 5302, zeta-cypermethrin, zolaprofos, ( 1 R-cis)-[5-(phenylmethyl)-3-furanyl]-methyl-3-[(dihydro-2-oxo-3(2H)-furanyl-idene)-methyl]-2,2-dimethylcyclopropanecarboxylate, (3-phenoxyphenyl)-methyl 2,2,3,3-tetramethylcyclopropanecarboxylate, 1-[(2-chloro-5-thiazolyl)methyl]tetrahydro-3,5-dimethyl-N-nitro-1,3,5-triazine-2( 1 H)-imine, 2-(2-chloro-6-fluorophenyl)-4-[4-(l,l-dimethylethyl)phenyl]-4,5-dihydro-oxazole, 2-(acetyloxy)-3-dodecyl-1,4-naphthalenedione, Le A 33 687-Foreign Countries 2-chloro-N-[[[4-( 1-phenylethoxy)-phenyl]-amino]-carbonyl]-benzamide, 2-chloro-N-[[[4-(2,2-dichloro-l,1-difluoroethoxy)-phenyl]-amino]-carbonyl]-benzamide, 3-methylphenyl propylcarbamate, 4-[4-(4-ethoxyphenyl)-4-methylpentyl]-1-fluoro-2-phenoxy-benzene, 4-chloro-2-( 1,1-dimethylethyl)-5-[[2-(2,6-dimethyl-4-phenoxyphenoxy)ethyl]thio]-3(2H)-pyridazinone, 4-chloro-2-(2-chloro-2-methylpropyl)-5-[(6-iodo-3-pyridinyl;)methoxy]-3(2H)-pyridazinone, 4-chloro-5-[(6-chloro-3-pyridinyl)methoxy]-2-(3,4-dichlorophenyl)-3(2H)-pyridazinone, Bacillus thuringiensis strain EG-2348, [2-benzoyl-1-(1,1-dimethylethyl)-hydrazinobenzoic acid, 2,2-dimethyl-3-(2,4-dichlorophenyl)-2-oxo-1-oxaspiro[4.5]dec-3-en-4-yl butanoate, [3-[(6-chloro-3-pyridinyl)methyl]-2-thiazolidinylidene]-cyanamide, dihydro-2-(nitromethylene)-2H-1,3-thiazine-3(4H)-carboxaldehyde, ethyl [2-[[1,6-dihydro-6-oxo-1-(phenylmethyl)-4-pyridazinyl]oxy]ethyl]-carbamate, N-(3,4,4-trifluoro-1-oxo-3-butenyl)-glycine, N-(4-chlorophenyl)-3-[4-(difluoromethoxy)phenyl]-4,5-dihydro-4-phenyl-1H-pyra~ole-1-carboxamide, N-[(2-chloro-5-thiazolyl)methyl]-N'-methyl-N"-nitro-guanidine, N-methyl-N'-( 1-methyl-2-propenyl)-1,2-hydrazinedicarbothioamide, N-methyl-N'-2-propenyl-1,2-hydrazinedicarbothioamide, O,O-diethyl [2-(dipropylamino)-2-oxoethyl]-ethylphosphorarnidothioate.
The active compounds according to the invention can furthermore be present in their commercially available formulations and in the use forms, prepared from these formulations, as a mixture with synergistic agents. Synergistic; agents are compounds which increase the action of the active compounds, without it being necessary for the synergistic agent added to be active itself.

Le A 33 687-Foreign Countries Ready-to-use preparations comprise the active compound in concentrations of from ppm to 20% by weight, preferably from 0.1 to 10% by weight.
Preparations which are diluted prior to use comprise the active compound in 5 concentrations of from 0.5 to 90% by weight, preferably from 5 to 50% by weight.
In general, it has been found to be advantageous to administer amounts of from about 1 to 100 mg of active compound per kilogram of body weight per day to obtain effective results.

Le A 33 687-Foreign Countries Preparation Examples Example 1 Cyclo( N methyl-L-1eutipy1-D-(hydroxy-imino)-lactyl-N methyl-L-1eutipy1-D
phenyl-lactyl-N methyl-L-1eutipy1-D-lactyl-N methyl-L-1eutipy1-D phenyllactyl J
Me HBO Me p Me N ~ O ~''~"..
Me N ' N O
Me0 ~ Me Me O O
O Me Me Me' O N N
Me Me ~ ,M'e1~0~~ Me a) according to process 2a using mercury(II) acetate 20Q.0 mg (0.20 mmol) of cyclo(-N-methyl-L-1eutipy1-D-thiolactyl-N-methyl-L-.~-.. 1eutipy1-D-phenyllactyl-N-methyl-L-1eutipy1-D-lactyl-N-methyl-L-1eutipy1-D-phenyllactyl-) (cf. WO 98/43 965) in 5 ml of acetonitrile are treated successively with 43.6 mg (0.62 mmol) of hydroxylamine hydrochloride, 145.0 mg (0.45 mmol) of mercury(II) acetate and 162.2 mg (1.25 mmol) of ethyldiisopropylamine ("Hiinig's Base"), and the mixture is stirred at room temperature for l8 hours. To bring the reaction to completion, another 21.8 mg (0.31 mmol.) of hydroxylamine hydrochloride, 72.5 mg (0.45 mmol) of mercury(II) acetate and 107.4 mg (1.25 mmol) of ethyldiisopropylamine ("Hiinig's Base") are added, and the mixture is stirred at room temperature for another 6 hours. The entire reaction mixture is then stirred into about 20 ml of aqueous NH4C1 solution and extracted four times with 15 ml of chloroform. The crude product that remains is chromatographed over a Le A 33 687-Foreign Countries silica gel column (silica gel 60 - Merck, particle size: 0.04 to 0.063 mm) using the mobile phase cyclohexane : acetone ( 4 : 1 ).
This gives 70.4 mg (35% of theory) of cyclo[-N-methyl-L-leucinyl-D-(hydroxyimi-no)-lactyl-N-methyl-L-leuc inyl-D-phenyl lactyl-N-methyl-L-leucinyl-D-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-] as anti-/syn-isomer mixture.
b) according to process 2a using mercury(II] chloride / mercury(II) acetate The reaction with hydroxylamine hydrochloride is carried out similarly to the reaction procedure of Example 1 (Variant a) using:
500.0 mg (0.52 mmol) of cyclo(-N-methyl-L-leucinyl-D-thiolactyl-N-methyl-L-leucinyl-D-phenyllactyl-N-methyl-L-leucinyl-D-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-) 107.9 mg (1.55 mmol) of hydroxylamine hydrochloride 422.0 mg (1.55 mmol) of rnercury(II) chloride 230.2 mg (1.81 mmol) of ethyldiisopropylamine ("Hunig's Base") 30 ml of tetrahydrofuran After 20 hours of stirring at 50°C, another 180.0 mg (0.56 mmol) of mercury(II) acetate are added, and stirring is continued at 50°C for another 24 hours. The entire reaction mixture is then filtered and worked up as under Example 1 (Variante a).
Yield: 250 mg (50% of theory) b) according to process 3a by hydrogenation of derivative 17 400.0 mg (0.37 mmol) of cyclo[-N-methyl-L-leucinyl-D-(benzyloxyimino)-lactyl-N-methyl-L-leucinyl-D-phenyl(actyl-N-methyl-L-leucinyl-D-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-] 17 (cf. Table 1) are stirred in 40 ml of methanol and, in the Le A 33 687-Foreign Countries presence of 200 mg of Pd/carbon [palladium content 10'%) and 0.7 ml of conc.
hydrochloric acid, hydrogenated at room temperature until hydrogen uptake has ended (about 20 minutes). The catalyst is filtered off and the entire reaction solution is then concentrated under reduced pressure and the crude product that remains is chromatographed over an RP-18 column using the mobile phase acetonitrile :
water.
Yield: 110 mg (30% of theory) c) according to process 3b by deblocking from a polymeric resin support A mixture of 100 mg cyclodepsipeptide-containing polystyrene resin, 3.0 ml of n-butanol and 3.0 ml of 1,2-dichloroethane is treated with 8.5 mg of pyridine para-toluenesulfonic acid and stirred at 60°C for one hour. The polystyrene resin is then filtered off and washed five times with methylene chloride. Concentration under reduced pressure gives 9.4 mg of crude product in which Example 1 could be demonstrated by APCI-MS.
LC-MS (acidic) m/z (%): 964 (M+, 100). C52H~~N5012 (964.2) Rt - value (HPLC column: 125 x 2.1 Kromasil ~, C-18): 17.4; 17.66 min; anti-/syn-isomer mixture (20:80).

Le A 33 687-Foreign Countries Example 2 Cyclo~ N methyl-L-leucinyl-D-(O-methyl-imino)-lactyl-N methyl-L-leucinyl-D
phenyl-lactyl-N methyl-L-leucinyl-D-lactyl-N methyl-L-leucinyl-D phenyllactyl J
Me Me Me,O Me O
N ~., O
Me N \ N O
Me0 ~ Me Me '""'"'' O O
O Me Me Me\
O N N
Me Me ~ ,M'e' 0~ MY '~e The reaction with an O-substituted amine component was carried out similarly to the reaction procedure of Example 1 using:
200.0 mg (0.20 mmol) of (-N-methyl-L-leucinyl-D-thiolactyl-N-methyl-L-leucinyl-D-phenyllactyl-N-methyl-L-leucinyl-D-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-) 52.4 mg (0.62 mmol) of O-methyl-hydroxylamine hydrochloride 145.0 mg (0.45 mmol) of mercury(II) acetate 162.2 mg (1.25 mmol) of ethyldiisopropylamine ("Hiinig's Base") 5 ml of acetonitrile The crude product that remains is chromatographed over a silica gel columne (silica gel 60 - Merck, particle size: 0.04 to 0.063 mm), initially using the mobile phase cyclohexane : acetone ( 4 : 1 ). This gives 170 mg (83% of theory) of cyclo[-N-methyl-L-leucinyl-D-(O-methyl-imino)-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-N-methyl-L-leucinyl-D-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-] .

Le A 33 687-Foreign Countries 'H-NMR (600 MHz, CDC13, 8): 2.85; 2.87; 2.90; 3.04 (4 x N-CH ); 3.65 (-O-CH , oxime) ppm.
13C-NMR (100 MHz, CDCl3, 8): 29.3; 30.2; 30.9; 31.0 (4 x N-CH ); 61.3 (-O-CH3, oxime); 66.9; 68.1; 69.7; 71.1; (4 x -CH-O-); 56.9; 53.9; 53.9; 59.5 (4 x -CH-N-);
170.3; 170.3; 172.5; (3 x -N-C=O); 152.9 (1 x -C=N-O, oxime); 170.2; 170.7;
171.1;
172.5 (4 x -O-C=O) ppm.
LC-MS (acidic) m/z (%): 978 (M+, 100). CS3H~91V50~2 (978.x') R~ - value (HPLC column: 125 x 2.1 Kromasil ~, C-18): 18.34 min Le A 33 687-Foreign Countries _87_ Example 3 Cyclo~ N methyl-L-leucinyl-D-(O-acetyl-imino)-lactyl-N methyl-L-1eutipy1-D-phenyl-lactyl-N methyl-L-1eutipy1-D-lactyl-N methyl-L-1eutipy1-D phenyllactyl J
S

~ Me Me Me" p Me O
N w ":
~O~
Me~ N' N O
Me0 Me Me O O
O Me Me Me O N \N
O Me Me M''e11~'O~~// Me 200.0 mg (0.20 mmol) of 1 (see Ex. 1 ) are treated in 1 ml of acetic anhydride and stirred at 70°C for about 30 minutes. The entire reaction mixture is then treated with saturated NaHC03 solution and extracted three times with 15 ml of ethyl acetate. The organic phase is separated off, dried over magnesium sulfate and concentrated under reduced pressure. The crude product that remains is chromatographed over a silica gel columne (silica gel 60 - Merck, particle size: 0.04 to 0.06:3 mm) using the mobile phase cyclohexane : acetone ( 10 : 1 ). This gives 125.8 mg (fi0% of theory) of crude product which, after preparative HPLC (RP-18), gives 80 mg (38% of theory) of pure cyclo[-N-methyl-L-1eutipy1-D-(O-acetyl-imino)-lactyl-N-methyl-L-1eutipy1-D-phenyllactyl-N-methyl-L-1eutipy1-D-lactyl-N-methyl-L-1eutipy1-D-phenyl-lactyl-] as anti/syn isomer mixture (purity: 98.7%).
LC-MS (acidic) m/z (%): 1006 (M+, 100). C$4H7gNSO~3 (1006.2) R~- value (HPLC column: 125 x 2.1 Kromasil ~, C-18): 7.35 min Le A 33 687-Foreign Countries _88_ Examale 4 Cyclo~ N methyl-L-leucinyl-D-(O-vinylo~ycarbonyl-imino)-lactyl-N methyl-L-leucinyl-D phenyllactyl-N methyl-L-leucinyl-D-lactyl-N methyl-L-leucinyl-D-phenyllactyl J

Me ~O~ O Me O Me r N ~ O ~,~,, Me N ' N O
Me0 ~ Me Me O O
O Me Me Me / O N \N
O Me Me ~ Me'0I ~~,~Me At 0°C, 300.0 mg (0.31 mmol) of 1 (see Ex. 1) are stirred in 10 ml of dry pyridine and treated with 99.4 mg (0.93 mmol) of vinyl chloroformate. Stirring at 0°C is then continued for another 6 hours. The entire reaction mixture is then concentrated under reduced pressure and the residue is taken up in chloroform and washed once with 1N HCI and twice with NaE-IC03 solution. The organic phase is separated off and dried over magnesium sulfate and then concentrated under reduced pressure, and the crude product that remains is chromatographed over a silica gel column (silica gel 60 - Merck, particle size: 0.04 to 0.063 mm) using the mobile phase cyclohexane :
ethyl acetate {2 : 1). This gives 188.7 mg (58.7% of theory) of cyclo[-N-methyl-L-leucinyl-D-(O-vinyloxycarbonyl-imino)-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-N-methyl-L-leucinyl-D-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-] as anti/syn isomer mixture.
LC-MS (acidic) mlz (%): 1037 (MH+, 100) CSSHB~NSC)~Q (103b.2) RL- value (HPLC column: 125 x 2.1 I~romasil ~, C-18): 17.82 min Le A 33 687-Foreign Countries Example 5 Cyclo~ N methyl-L-1eutipy1-D-(D-methylsulfonyl-imino)-lactyl-N methyl-L-leucinyl-D phenyllactyl-N methyl-L-1eutipy1-D-lactyl-N methyl-L-1eutipy1-D phenyllactyl J

Me Me~~ O Me O Me N ~.. O .".
Me N ' N O
MeO~ Me Me O O
O Me Men O N
N Me ""~~O~O
Me ~ Me0 Me The reaction with methanesulfonyl chloride is carried out similarly to the reaction procedure of Example 4 using:
200.0 mg {0.20 mmol) of cyclo[-N-methyl-L-1eutipy1-D-(hydroxy-imino)-lactyl-N-methyl-L-1eutipy1-D-phenyl-lactyl-N-methyl-L-1eutipy1-D-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-] (Ex. 1) 71.3 mg (0.62 mmol) of methanesulfonyl chloride 8 ml of dry pyridine The crude product that remains is chromatographed over a silica gel column (silica gel 60 - Merck, particle size: 0.04 to 0.063 mm) initially using the mobile phase cyclohexane : ethyl acetate (3 : 2). This gives 81.8 mg (38% of theory) of cyclo[-N-methyl-L-1eutipy1-D-(O-methylsulfonyl-imino)-lactyl-N-methyl-L-1eutipy1-D-phenyllactyl-N-methyl-L-1eutipy1-D-lactyl-N-methyl-L-1eutipy1-D-phenyllactyl-]
as antilsyn isomer mixture.

Le A 33 687-Foreign Countries LC-MS (acidic) m/z (%): 1042 (MH+, 100). C53H~9Ng014S (1042.3) R~- value (HPLC column: 125 x 2.1 Kromasil ~, C-18): 17.18 min Le A 33 687-Foreign Countries Example 6 Cyclo~ N methyl-L-1eutipy1-D-(O-allylaminocarbonyl-imino)-lactyl-N methyl-L-leucinyl-D phenyllactyl-N methyl-L-1eutipy1-D-lactyl-N methyl-L-1eutipy1-D-phenyllactyl J

~ Me ~N~O Me O Me H N .., O
Me N\ ~N O
Me Me Me0 O O
O
Me Me Me O' _N \N
O Me Me ~''M''e'' 0~~ 'Me 300.0 mg (0.31 mmol) of cyclo[-N-methyl-L-1eutipy1-D-(hydroxy-imino)-lactyl-N-methyl-L-1eutipy1-D-phenyl-lactyl-N-methyl-L-1eutipy1-D-lactyl-N-methyl-L-1eutipy1-D-phenyl-lactyl-] (Ex. 1) in 10 ml of abs. toluene are treated successively with 30.4 mg (0.36 mmol) of allyl isocyanate and 2 drops of 1,8-diazabicyclo[5.4.0]undec-7-ene {"DBU") and stirred at roam temperature for 33 hours. The entire reaction mixture is then concentrated under reduced pressure. The crude product which remains is initially chromatographed over a silica gel column (silica gel 60 - Merck, particle size: 0.04 to 0.063 mm) using the mobile phase cyclohexane : acetone (3 : 1 ) and then over a second silica gel column (silica gel 60 -Merck, particle size: 0.04 to 0.063 mm) using the mobile phase cyclohexane :
ethyl acetate (2 : 1 to 1 : 1). This gives 52.4 mg (16.1% of theory) of cyclo[-N-methyl-L-leucinyl-D-(O-allylaminocarbonyl-imino)-lactyl-N-methyl-L-1eutipy1-D-phenyllactyl-N-methyl-L-1eutipy1-D-lactyl-N-methyl-L-leucin,yl-D-phenyllactyl-] as anti/syn isomer mixture.
LC-MS (acidic) m/z (%): 1047 (M+, 100). C56H81N6O1j (104'7.3) RL- value {HPLC column: 125 x 2.1 Kromasil ~, C-18, pH 2.3): 17.09; 17.39 min Le A 33 687-Foreign Countries Example 7 Cyclo( N methyl-L-leucinyl-D-(O-N tert-butyloxycarbonyl-71~ methyl-alanyl-imino)-lactyl-N methyl-L-leucinyl-D phenyllactyl-N methyl-L-leucirayl-D-lactyl-N
methyl-L-leucinyl-D phenyllactyl J
Me O
Me~O~N~ Me Me O Me O
Ma O Me N
O
Me N' ~ N O
Me Me Me0 O O
~ a Me\ O Me O N N
O Me Me ~ Me O ''''Me At 0°C, 184.0 mg (4.1 mmol) of benzotriazol-1-yl-oxy-tris(dimethylamino-phosphonium) hexafluorophosphate (BOP) and 124.0 mg (0.95 mmol) N,N-diisopropylethylamine ("Hiinigs Base") are added to a solution of 300.0 mg (0.3 F mmol) of cyclo[-N-methyl-L-leucinyl-D-(hydroxy-imino)-lactyl-N-methyl-L-leucinyl-D-phenyl-lactyl-N-methyl-L-leucinyl-D-lactyl-N-me-thyl-L-leucinyl-D-phenyl-lactyl-] (Ex. 1) and 75.7 mg (0.37 mmol) of N-tent-butyloxy-carbonyl-N-methyl-alanine in 10 ml of abs. acetonitrile, and the mixture is stirred at 0°C for 30 minutes and then at room temperature for 24 hours. The entire reaction mixture is then concentrated under reduced pressure, the residue is taken up in chloroform and extracted twice with water and the organic phase is separated off, dried over sodium sulfate and then concentrated under reduced pressure. The crude product that remains is purified by preparative HPLC. This gives 15.6 mg (4.4% of theory) of cyclo[-N-methyl-L-leucinyl-D-(O-N-tert-butyloxycar-bonyl-N-methyl-alanyl-imino)-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-N-methyl-L-leucinyl-D-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-] as anti/syn isomer mixture.

Le A 33 687-Foreign Countries LC-MS (acidic) m/z (%): 1150 (MH+, 100). C6~H91N6O~s (1149.4) R,- value (HPLC column: 125 x 2.1 Kromasil ~, C-18): 7.69; 7.76 min The com ounds of the formula Ia R' R3 R4 R' R9 R'°; -Me' RZ RS Rg R": -P ( )( > > > > > > > > >
iso-butyl; XZ: =N-A; X2-X4: =O) listed in Table 1 below can be prepared analogously.

Le A 33 687-Foreign Countries Table 1 ~~Me A Me ~J'O
N~O~,~
Me N ' fN O ~ R"
MeO~ Me Me O O
O Me Me Me' R' ~ O N N Me (Ia) O~O
Me ~ Me0 Me Ex. -A R' R" Physical data a No.

993 (MH+, 100); R~: 20.05 8 -O-CH2-Me -H -H

C'sal~s~NsW z (992.2) 1005 (MH+, 100); R~:
20.21;
9 -O-CH2-CH=CHz -H -H 20.31 (anti/syn isomer mixture) - Css~~a~Ns~m (1048.3) 1006 (MH+, 100); Rt:
13.75 -O-CHZ-CH2-Me -H -H

CssH8.~s4m (1006.3) 1006 (MH~~, 100); Rt:
13.54 11 -O-CHMe2 -H -H

CssF.~83Ns~12 (100b.3) Le A 33 687-Foreign Countries Table 1 (Continued) Ex. -A R' R" Physical T)ata a No.

1006 (MH+, 100); R~:
22.52;

12 -O-CMe3 -H -H 22.85 ,.~. (anti/syn isomer mixture) Css~~ssNsW 2 (1006.3) 1003 (M+, 100); Rt: 7.49 Csa~~~sN641a (1003.2) 1008 (M+, 100); R~: 17.58 Cs~BlNs013 (1 x08.2) 1008 {MH ~, 100) Cs4~~81N6~11 (1 ~~7.3) 978 {MH+, 100); R~: 18.33 16 -NHMe -H -H

Cs3~~80N6011 (977.2) 1055 (MH+, 100); R,:
21.23;

17 -O-CH2-phenyl -H -H 21.50 (anti/syn isomer mixture) Cs9H83Ns~12 (1054.3) 1100 (MH+, 100); Rt:
20.50 18 -O-CH2-(4-N02-phenyl)-H -H

Cs9H82N6~14 (j 099. 3) Le A 33 687-Foreign Countries Table 1 (Continued) Ex. -A R' R" Physical Data a No.

1099 (M+, 100); Rt:
19.06 19 -O-CHZ-(2-NOZ-phenyl)-H -H

Cs9H~2N60,4 (1099.3) 1123 (MH+, 100);

20 -O-CHZ-(3-CF3-phenyl)-H -H R,: 19.50; 19.68 (anti/syn isomer mixture) C6oN~~zNsW z (1122.3) 1123 (MH+, 100); Rt:
19.43 21 -O-CH2-(4-CF3-phenyl)-H -H

C6oHdINSOl2 (1122.3) 1088 (MH+, 100) 22 -O-CHZ-(2-Cl-phenyl)-H -H Rt: 19.65; 20.07 (anti/syn :isomer mixture) C's~s.~CINs0~2 (1088.7) ",~ 1088 (MH+, 100) 23 -O-CHZ-(3-Cl-phenyl)-H -H Rt: 19.61; 19.78 Cs9H8 ~CINSOII (1088.
7) 1088 (MH:+, 100);

24 -O-CH2-(4-Cl-phenyl)-H -H R,: 19.65; 19.82 (anti/syn iisomer mixture) Cs9H8,eClNsOl1 (1088.7) 1124 (MH:+, 100);

25 -O-CH2-(3,4-Cl2-phenyl)-H -H Rt: 20.14; 20.40 (anti/syn isomer mixture) Csv~a~ClzNs0~2 (1123.2) Le A 33 687-Foreign Countries Table 1 (Continued) Ex. -A R' R" Physical Data a No.

1124 (MH*, 100);

26 -O-CH2-(2,6-C12-phenyl)-H -H R~: 19.82; 20.12 (anti/syn isomer mixture) CspNB~CIzNs4~a (1123.2) 1124 (MH*, 100);

27 -O-CH2-(2,4-Cl2-phenyl)-H -H R~: 20.68; 21.16 (anti/syn isomer mixture) Cs9H8,C11Ns4m (1123.2) 1124 (MHO, 100);

28 -O-CH2-(2,3-Cl2-phenyl)-H -H R,: 20.32; 20.79 (anti/syn isomer mixture) Cs9H8~(:IzN50~2 (1123.2) 1106 (M*, 100);

29 -O-CH2-(2-C1,6-F-phenyl)-H -H R,: 19.24; 19.44 (anti/syn isomer mixture) Cs9H8l(:IFN50~2 (1106.8) 1084 (MH*, 100); R,:
18.97 30 -O-CH2-(4-Me0-phenyl)-H -H

C6oH85N5O~3 (1084.3) 1112 (MH*, 100); R,:
18.89 31 -O-CH2-(4-Me00C-phenyl)-H -H

CsoHssNsW s (1112.3) 1072 (MH*, 100); R~:
19.48 32 -O-CH2-(4-F-phenyl) -H -H

CsvHBZ~'Ns~m (1072.3) Le A 33 687-Foreign Countries Table 1 (Continued) Ex. -A R' R" Physical Data a No.

1068 (M+" 100); R~: 19.95 33 -O-CHZ-(4-Me-phenyl) -H -H

CaoHsaNs4i2 (1068.3) 964 (MH+, 100); R~: 16.24 C51H78N6~11 (963.2) 1022 (MH+, 100); Rt:
7.32 35 -O-CO-O-Me -H -H

CsaHwNs4~a (1022.2) 1036 (MH+, 100); Rt:
17.69 36 -O-CO-O-CHZ-Me -H -H

CssHsrNs4~a (1036.2) 1048 (MH+, 100); R,:
17.83 37 -O-CO-O-CH2-CH=CHz -H -H
, CssHBrNsW a (1048.3) 1046 (M+, 38); R,: 7.32 C56H79NSOI4 (1046.3) 1064 (MH~~, 100); R~:
18.28 39 -O-CO-O-CHMe-CHz-Me -H -H

Cs~HssNsO,a (1064.3) 1064 (MH*, 100); Rt:
18.33 40 -O-CO-O-CH2-CHMez -H -H

Cs~NsslVs0~4 (1064.3) Le A 33 687-Foreign Countries Table 1 (Continued) Ex. -A R' R" Physical Data a No.

1116 (MH ~, 100); Rt:
18.01 41 -O-CO-O-CHZ-CHZ-CF=CFZ-H -H

Cs7H80~'.3Ns~14 (1116.3) 42 -O-SOZ-CHz-CHZ-O-CHz--H -H Cs6HszF3IVsSOrs (1154.3) 0 1076 (MHO-, 100); Rt:
o~ 18.01 43 N _H _H
~

Cs8H86N6~13 (1 X7.5.3) 1091 (M+, 100); R,: 17.64 44 ~ -H -H

Cs8H86N6~14 (1091.3) ~. O
1049 (MH+, 100); R,:
19.94 45 (s) O -H -H
, '~," C's~HssNs4~3 (1048.3) 1044 (M+, 100); R,: 18.73 CssHs~.NsOla (1044.3) 1045 (MH+, 100); Rt:
O 18.86 47 ~ -H -H

CssHs3NsW a (1044.3) CI 1096 (MH+, 100);

S

48 ~ O ~ , N -H -H R~: 18.82; 19.02 N ' (anti/syn isomer mixture) CssH~sC.'IN~0~1S (1096.8) Le A 33 687-Foreign Countries Table 1 (Continued) Ex. -A R' R" Physical Data a No.

Me, 1060 (MH+, 100);

N-N
49 .~ o ~ 'N -H -H Rt: 17.5 8; 17.70 N
(anti/syn isomer mixture) "~..
CssHsrN9W z (1059.8) 1055 (M+, 100); R,: 18.08 ~ ~
I

50 ' -H -H
N

Cs8H82N6012 (1 ~.s.s.3) -- ci 1089 (M+, 100); R~: 18.87 ~ o 51 \ N -H -H

CssHsW1N64u (1089.7) 1084 (M+, 100); Rt: 19.34 52 ~O \ ~ -H -H

C60H8sNs~73 (1084.3) . ~ o ~- 1152 (M+, 100); Rt: 19.80 ~

,~,... 53 o \ / _H _H

C61H84F3Ns013 (1152.3) 1059 (M+, 100); R~: 17.69 ~

54 ~ -H -H

Cs~H~9Ns4,Q (1058.3) 1139 (M+, 100); R,: 11.24 55 -O-CH2-(4-N-morpholino--H -H

phenyl) C63H9PN6~13 iH_NMR (400 MHz, 8, ppm); ~3C-NMR (100 MHz, 8, ppm); LC-MS (acidic) m/z (%);
Rt-value (min, HPLC column: 125 x 2.1 Kromasil °, C-18) Le A 33 687-Foreign Countries Example I-56 Reaction of the polymer-bound hydroxylamine with cyclo[-N-methyl-L-leucinyl-thiolactyl-N-methyl-L-leucinyl-D-phenyllactyl-N-methyl-L-leucinyl-D-lactyl-N-S methyl-L-leucinyl-D-phenyllactyl-]
The reaction of 6-(amino-oxy)-3,4,5,6-tetrahydro-2H-pyran-2-yl-methoxymethyl-polystyrene with the cyclothiodepsipeptide is carned out similarly to the reaction procedure of Example 1 (variant a) using:
500.0 mg (0.52 mmol) of cyclo(-N-methyl-L-leucinyl-D-thiolactyl-N-methyl-L-leucinyl-D-phenyllactyl-N-methyl-L-leucinyl-D-lactyl-N-methyl-L-leucinyl-D-phenyllactyl-) 200.0 mg of 6-(amino-oxy)-3,4,5,6-tetrahydro-2H-pyran-2-yl-methoxy-methyl-polystyrene 181.0 mg ( 1.55 mmol) of mercury(II) acetate 15 ml of dichloromethane The 6-(amino-oxy)-3,4,5,6-tetrahydro-2H-pyran-2-yl-methoxymethyl-polystyrene resin is initially stirred at room temperature in dichloromethane for 30 minutes and then Heated with the cyclothiodepsipeptide and mercury(II) acetate. The polystyrene resin is then separated off and washed successively in each case three times with dichloromethane, dimethylformamide/water ( 1:1 ), dimethylformamide and dried under high vacuum.
Yield: 180 mg of polystyrene resin IR (KBr): 1730 cm'' (vC~; cyclodepsipeptide) Le A 33 687-Foreign Countries Starting materials ofthe formula (1b) Example ( Ib -1 ) Cyclo~ N methyl-L-leucinyl-D-thiolactyl-N methyl-L-1eutipy1-D phenyllactyl-N
methyl-L-1eutipy1-D-thiolactyl-N methyl-L-1eutipy1-D phenylthiolactyl Me Me Me O
S~O
Me N \ N S
MeO~ Me Me O O
O
Me Me Me S' _N \N
~O~S Me Me Me IO' Me 1.0 g (1.05 mmol) of cyclo(-N-methyl-L-1eutipy1-D-lactyl-N-methyl-L-1eutipy1-D-phenyl-lactyl-N-methyl-L-1eutipy1-D-lactyl-N-methyl-L-1eutipy1-D-phenyllactyl-) PF 1022A (cf. EP-A 382173, US-Pat. 511681 S) in 20 ml of toluene were treated with 1.4 g (3.5 mmol) of 2,4-bis-(4-methoxy-phenyl)-2,4-dithioxo-1,3,2,4-.
dithiadiphosphetane ("Lawesson's Reagent") and stirred at reflux temperature for 3.5 hours. The entire reaction mixture is then cooled to 0°C and filtered and the resulting filtrate is concentrated under reduced pressure. The crude product that remains is chromatographed over a silica gel column (silica gel 60 - Merck, particle size: 0.04 to 0.063 mm) using intially the mobile phase methylene chloride and then the mobile phase cyclohexane : acetone (3 : 1 ). This gives 0.46 g (43.6% of theory) of cyclo(-N-methyl-L-1eutipy1-D-thiolactyl-N-methyl-L-1eutipy1-D-phenylthiolactyl-N-methyl-L-leu-cinyl-D-thiolactyl-N-methyl-L-1eutipy1-D-phenylthiolactyl-).
'H-NMR (CDCl3, S): 2.99, 3.06, 3.26, 3.42 (4 x -N-Me); 4.86, 6.42, 6.61 (4 x -N-CH2-);

Le A 33 687-Foreign Countries 5.31, 5.55, 5.81, 5.89 (4 x -O-CHZ-); 7.26 (phenyl-H) ppm.
LC-MS (acidic) m/z (%): 1013 (M+, 100); 310 (21); 274 (30); 198 (42).
C,slH~61V408S4 (1013.4) Le A 33 687-Foreign Countries Example (1b - 2) Cyclo( N methyl-L-1eutipy1-D-thiolactyl-N methyl-L-1eutipy1-D phenyllactyl-N
methyl-L-1eutipy1-D-lactyl-N methyl-L-1eutipy1-D phenyllactyl Me ~ Me Me O
S~O
MeN' N O
Me0 ~ Me Me O O
O
Me Me Me O"N \N
Me O
MeMeO Me At 0°C, 1.0 g ( 1.05 mmol) of cyclo(-N-methyl-L-ieucinyl-D-lactyl-N-methyl-L-1eutipy1-D-phenyl-lactyl-N-methyl-L-1eutipy1-D-lactyl-N-methyl-L-1eutipy1-D-phenyllactyl-) PF 1022A (cf. EP-A 382173, US-Pat. 5116815) in 15 ml of tetrahydrofuran was treated with 0.26 g (0.05 mmol) of 2,4-bis-(4-phenoxy-phenyl)-2,4-dithioxo-1,3,2,4-dithiadiphosphetane ("Belleau's Reagent") and stirred at room temperature for 18 hours. The entire reaction mixture is then concentrated under reduced pressure. The crude product that remains is chromatographed twice over a silica gel column (silica gel 60 - Merck, particle size: 0.04 to 0.063 mm) using the mobile phase cyclohexane : acetone (3 : 1). This gives 0.12 g (11.8% of theory) of cyclo(-N-methyl-L-1eutipy1-D-thiolactyl-N-methyl-L-1eutipy1-D-phenyllactyl-N-methyl-L-1eutipy1-D-lac-tyl-N-methyl-L-1eutipy1-D-phenyllactyl-).
LC-MS (acidic) m/z (%): 965 (M+, 100); 200 (45).
C52H~6N40"S (965.2) The compounds of the formula (Ib) (R', R3, R4, R', R9, R1°: -Me; R2, R5, Rg, Rrl:
iso-butyl) listed in Table 2 below can be prepared analogously.

Le A 33 687-Foreign Countries Table 2 Me ~ Me Me O
X~~O~,, Me N ' ~N X2 ,,~ R"
MeO~ Me Me /
O O
~Me Met O Me R' X, N N ~ Me .~O~X3 Me ~Me~O Me Ex. X' Xz X3 X4 R' R" Physical Data $~
No.

3.04, 3.09, 3.25, 3.50 (4 x -N-Me);

4.87, 6.38, 6.56, 6.63 (4 x -N-CHZ-);

Ib S S S S -NOz -NO~ 5.31, 5.52, 5.81, - 5.91 (4 x -O-CH2-);

8.17; 7.46 (aryl-H).

1103 (MH+, 100); 392 (38);

177(40); 136 (30).
CSZHlV6O,z,S, (l 103.4) 1056 (M+H, 39).

Ib S O O O -NO~ -NOZ CSZH7alV6O, jS (1055.26) -Ib 1184 (MH', 100); 986 - ( 13); 593 S S S S j ~ j ~ (32); 392 (73); 177 (78).

C6~90N6~1~J (1183.6) Ib ~ 1135 (M+, 56); 361 - S O O O N~ N~ ( 100).
6 5 (1135 C
~
~

/ / .
) Le A 33 687-Foreign Countries Table 2 (Continued) Ex. X~ XZ X'X4 R' R" Physical Data's No.

F.: 120-125 C

3.15, 3.21, 3.42, 3.57 (4 x -N-Me);

o ~ ~ 5.03, 6.55, 6.78 (4 x -N-CHZ-); 5.45, Ib S S S S o -H 5.69, 5.89-6.08 (4 - x -O-CHZ-); 7.05-'""""" 7.60 (aryl-H, furyl-H).

1109 (M+, 2); 1108 (3); 370 (15);

274 (32). C;,HBOIVfO,pS., (1109.54) Ib ro ~ ~ 1061 (MT, 100); 198 - (58).

S O O O o -H C;,H8aN~0, jS (1061.
3) F.: 107-110 C

3.01, 3.07, 3.26, 3.41 (4 x -N-Me);

Ib ~o ~ \ ~o ~ \ 4.96 (2 x -O-CHz-);
- 4.86, 6.42, 6.62 S S S S o o (4 x -N-CHZ-); 5.32, 5.56, 5.78, 5.85 (4 x -O-CHZ-); 6.91-7.44 (aryl-H, furyl-H).

1205 (M+, 3); 1204 (5); 370 (41);

198 ( 100). C6lHa,N.,O,iS, (1205.63) Ib !o ~ ~ o ~ ~ 1158 (MH+, 60); 391 - (28).

S O O O o o C6zH8,JVa~I;S (1157.4) Le A 33 687-Forei Countries Table 2 (Continued) Ex. X~ Xz X' X"R' R" Physical Data's No.

34.8, 35.2, 37.1, 39.2 (N-Me); 71.8, 73.3, 75.4 (-C_H-O-);
40.1, 40.6 (-CH2-); 62.3, 62.5, 62.6 (-C_H-N-);

121.4, 122.8, 136.9, 149.4 (=C_H-, Py); 70.7 (-C_Hz-O-);
115.0, 130.9 (=CH-, phenyl); 203.2, 203.4, 204.8, 205.7 (N-C_=S);
Ib S S S S o I ~ 168.8, 169.5, O
C
=O

~ ~o .
N ~ (-N -_ ).

3.01, 3.19, 3.26, 3.41 (4 x -N-Me);

5.17 (2 x -O-CH -);
4.86, 6.41, 6.64, 6.66 (4 x -N-CH -);
5.31, 5.75, 5.57, 5.85 (4 x -O-CH -);
6.91, 7.16 (phenyl-H), 7.24, 7.51, 7.72, 8.59 (pyridyl-H).

1228 (MH+, 18); 383 (58); 224 ( 100).

C6~H8~6~1~~ (1227.68) 1181 (MH', 23); 383 Ib ~o ~ N ~o ~ ~ (100).
- N C6~H86N6~13 S

S O O O (1179. 5J

al 1H-NMR (400 MHz, 8, ppm); 13C-NMR (100 MHz, 8, ppm); LC-MS (acidic) m/z (%) Le A 33 687-Foreien Countries Starting materials of the formula (II) Example (II-1) a) (S)-N-[(Tetrahydrofur-2-yl)-methoxy]-phthalimide (cf. S. Bailey et al., J. Med. Chem. 34, 1991, pp. 57-65) N-O
O (s~
1.5 g ( 14.7 mmol) of (S)-tetrahydrofur-2-yl-methanol (A. Mravik et al., Tetrahedron:
Asymmetry 7 (5), 1996, pp. 1477-1484), 2.4 g (14.7 mmol) of N-hydroxy-phthalimide and 3.85 (14.7 mmol) of triphenylphosphine are stirred in 50 ml of THF
and, at 0°C (atmosphere of protective gas) treated with 3.4 g (19.5 mmol) of diethyl azodicarboxylate and stirred at room temperature for 18 hours. The entire reaction mixture is then concentrated under reduced pressure and the residue is taken up in ether and extracted twice with water. The crude product that remains is chromatographed over a silica gel column (silica gel 60 - Merck, particle size: 0.04 to 0.063 mm) using the mobile phase cyclohexane : acetone (6 : 1). This gives 1.7 g M
(46.8% of theory) of (S)-N-[(tetrahydrofur-2-yl)-methoxy]-phthalimide.
LC-MS-LOOP m/z (%): 248 (MH+, 100) C13Hi3NO4 (247.2) RI- value (HPLC column: 125 x 2.1 Kromasil ~, C-18): 7.56 min b) (S)-Tetrahydrofur-2-yl-methoxy-amine (s~

Le A 33 687-Foreign Countries 1.6 g (6.47 mmol) of (S)-N-[(tetrahydrofur-2-yl)-methoxyJ-phthalimide are stirred in 30 ml of methylene chloride, 0.6 g ( 12.9 mmol) of N-methyl-hydrazine are added at 0°C and the mixture is stirred at room temperature for 18 hours. The entire reaction mixture is then filtered and the filtrate is concentrated under reduced pressure. The crude product that remains is chromatographed over a silica gel column (silica gel 60 - Merck, particle size: 0.04 to 0.063 mm) using the mobile phase ethyl acetate. This gives 130 mg (17.2% of theory) of (S)-tetrahydrofur-2-yl-methoxy-amine.
LC-MS (acidic) m/z (%): 118 (MH+, 100). CSZH76N4~1IS (117.1) Le A 33 687-Foreign Countries Example (II-2 a) N-tert-Butyloxycarbonyl-amino-oxyacetomorpholide CH >
~N-O N
Me Me Me 2.0 g (10.5 mmol) of N-tert-butyloxycarbonyl-amino-oxyacetic acid (Novabiochem:
O1-63-0060) are stirred in 75 ml of methylene chloride and, at 0°C, treated with 3.1 g (24.0 mmol) of N,N-diisipropylethylamine (Hunig's Base), 3.1 g (12.0 mmol) of bis(2-oxo-3-oxazolidinyl)-phosphonium acid chloride (BOP-Cl) and stirred for minutes. 1.05 g (12.0 mmol) of morpholine are then added, and stirring at 0°C is continued for 6 hours. The reaction solution is extracted twice with water and the organic phase is separated off and, after drying over sodium sulfate, concentrated under reduced pressure. The crude product that remains is chromatographed over a silica gel column (silica gel 60 - Merck, particle size: 0.04 to 0.063 mm) using the mobile phase cyclohexane : acetone (3 : 1). This gives 1.0 g (37% of theory) of N-tert-butyloxycarbonyl-amino-oxyacetomorpholide.
1H-NMR (CDCl3, b): 1.47 (s, 9H, C(CH )3); 3.37-3.72 (3m, 8H, 2 x -N-CH -; 2 x -O-CH -;); 4.54 (s, 2H, -O-CH -); 8.06 (s, 1H, N-H) ppm.
LC-MS (acidic) m/z (%): 205 (M+- HZC=CMe2, 12), 161 (100). Cl~H2oN20s (260.3) R~- value (HPLC column: 125 x 2.1 Kromasil ~, C-18): 5.22 min b) Hydrochloride of the amino-oxyacetomorpholide Le A 33 687-Foreign Countries \ c+~
H-N-O N
H C~ ~_~
For 30 minutes, dry hydrogen chloride gas is introduced into a solution, cooled to 0°C, of 0.65 g (2.5 mmol) of N-tert-butyloxycarbonyl-amino-oxyacetomorpholide are into 220 ml of absolute methylene chloride. The mixture is then stirred at room temperature for about 16 hours and the entire reaction mixture is concentrated under reduced pressure. This gives 380 mg (77% of theory) of the hydrochloride of the amino-oxyacetomorpholide.
LC-MS (acidic) m/z (%): 161 (MH+-HCI, 100), 146 (12), 129 (45).
C6H,3C1N203 (196.6) Le A 33 687-Foreign Countries Examine (II-3) a) 6-(N-Succinimidyl-oxy)-3,4,5,6-tetrahydro-2H-pyran-2-yl-methoxymethyl-polystyrene resin P O
,N
O O
O
1.0 g (0.51 mmol) of DHP HM resin (Novabiochem: O1-64-0192) are allowed to swell in 8.0 ml of 1,2-dichloroethane for about 30 minutes. 293.5 mg (2.5 mmol) of N-hydroxy-succinimide and 261.4 g (1.0 mmol) of pyridinium para-toluenesulfonate (PPTS) are then added, and the mixture is stirred at 80°C for 16 hours.
The resin is then separated off and washed once with methylene chloride, four times with dimethylformamide/water ( 1:1 ), three times with dimethylformamide and three times with methylene chloride. The purified 6-(N-succinimidyl-oxy)-3,4,5,6-tetrahydro-2H-pyran-2-yl-methoxymethyl-polystyrene resin is dried under high vacuum and can be used for the subsequent reaction step.
IR (I~Br): 1730 cm 1 (vc~; succinimidyl radical) b) 6-(Amino-oxy)-3,4,5,6-tetrahydro-2H-pyran-2-yl-methoxymethyl-polystyrene P
NHZ
O O
Under an atmosphere of protective gas (argon), 1,0 g of 6-(N-succinimidyl-oxy)-3,4,5,6-tetrahydro-2H-pyran-2-yl-methoxymethyl-polystyrene resin is treated in 20 ml of benzene with 127.7 mg (2.55 mmol) of hydrazine hydrate and stirred under Le A 33 687-Foreign Countries reflux for 20 hours. The resin is then separated off, washed five times with methylene chloride and dried under high vacuum.
IR (KBr): 1630 cm-~ (V~_H deform. -~-NHz); 3300 cm"' (VN-H valences -C-NH2) The compounds of the formula (In (A= -Y-R~3) listed in Table 3 below can be prepared analogously to Examples II-1 and II-2 above.
Table 3 r 10 H

N-Y~
H (II) Ex. No. Y R'~ Physical Data's II - -O- ~ ' 149 (M+, 12);

p 5.02 (s, 2H, -CH -O-) :...

II - -O-149 (M+-HCI, 100) II - -O- N' 0 163 (MH+-HCI, 100);
6 Me (hydrochloride) Le A 33 b87-Forei,~.m Countries Ex. No. Y R" Physical Data's II - 7 -O- Me.,, 163 (MH'-HCI, 100);

N N (hydrochloride) N

"".......
II - 8 -O- / ~ 124 (MH+-2HCI, 100);

N
(dihydrochloride) 5.26 (br.
s -O-NH
) O
, , , ~

II - 10 -O- 145 (MH+-HCI, 100);
N

O (hydrochloride) ~., II - 11 -O- / ~ N O 207 (MH+-HCI, S);

4.91 (s, 2H, -CH -O-);
7.02;

7.28 (2d, 2x -CH -, morpholine) (hydrochloride) e~'H-NMR (400 MHz, 8, ppm); '3C-NMR ( 100 MHz, 8, ppm); LC-MS (acidic) m/z (%) Le A 33 687-Forei;~n Countries Biological Examples Example A
In vivo Nematode test Heterakis spumosa / Mouse Mice were experimentally infected with nematodes of the species Heterakis spumosa. To infect the mice, Heterakis spumosa was administered orally as 90 embryonate eggs.
After the prepatency period had expired, the suspended active compounds were administered intraperitoneally on day 46 after the infection.
Determination of the activity:
The mice are selected on day 54 after the infection. The adult parasites are counted in the colon and caecum using a microscope. The success of treatment in the dose group as compared to the untreated control group.
Active compounds tested and effective dosages (Dosis effectiva) are shown in the table below.

Le A 33 687-Foreign Countries Active compound Dosis effectivaReduction rate Example No. in [mg/kg] in [%]

Cyclo(-MeLeu-D-Lac-MeLeu-D-PhLac-25 p MeLeu-D-Lac-MeLeu-D-PhLac) PF 1022A,known a) Cyclo(-MeLeu-D-Lact-MeLeu-D-PhLac-""~.
MeLeu-D-Lac-MeLeu-D-PhLac) 25 p 1C1'IOWIl b) Ex. 1 according to the invention25 5-90 a) cf. EP-A 382 173, EP-A 503 538; b) cf. WO 98/43 965 MeLeu = N-methyl-L-leucine, D-Lac = D-lactic acid, D-PhLac =
D-phenyllactic acid, D-Lact = D-thiolactyl Le A 33 6$7-Forei~~n Countries Example B
In vivo Nematode test Nematospiroides dubius / Mouse Mice were experimentally infected with nematodes of the species Nemato~iroides dubius. To infect the mice, Nematospiroides dubius was administered orally as embryonate eggs.
After the prepatency period had expired, the suspended active compounds were administered intraperitoneally on day 46 after the infection.
Determination of the activity:
The mice are selected on day 54 after the infection. The adult parasites are counted in the colon and caecum using a microscope. The success of treatment in the dose group as compared to the untreated control group.
Active compounds tested and effective dosages (Dosis effectiva) are shown in the ...,.
table below.

Le A 33 687-Foreign Countries Active compound Dosis effectivaReduction Example No. in [mg/kg] rate in [%]

Cyclo(-MeLeu-D-Lac-MeLeu-D-PhLac-25 0 MeLeu-D-Lac-MeLeu-D-PhLac) PF 1022A knowna) "..,.., Cyclo(-MeLeu-D-Lact-MeLeu-D-PhLac-MeLeu-D-Lac-MeLeu-D-PhLac) 25 0 known b) Ex. 1 according to the invention25 100 e) cf. EP-A 382 173, EP-A 503 538; b) cf. WO 98/43 965 MeLeu = N-methyl-L-leucine, D-Lac = D-lactic acid, D-PhLac =
D-phenyllactic acid, D-Lact = D-thiolactyl Le A 33 687-Foreign Countries Example C
In vivo Nematode test S Haemonchus contortus / Sheep Sheep experimentally infected with Haemonchus contortus were treated after the end of the prepatency period of the parasite. The active compounds were administered orally and/or intravenously as pure active compound.
The efficacy is determined by quantitatively counting the worm eggs excreted with the faeces, before and after treatment.
Complete cessation of the excretion of eggs after treatment means that the worms have been expelled or are so severely damaged that they no longer produce any eggs (Dosis effectiva).
Active compounds tested and effective dosages (Dosis effectiva) are shown in the table below.

Le A 33 687-Foreien Countries Active compound Dosis effectivaReduction Example No. in [mg/kg) rate in [%) Cyclo(-MeLeu-D-Lac-MeLeu-D-PhLac-0.25 100 MeLeu-D-Lac-MeLeu-D-PhLac) 0.01 0 PF 1022A knowne~

Ex. 8 according to the invention0.01 100 Ex. 36 according to the invention0.01 100 Ex. 46 according to the invention0.10 100 cf. EP-A 382 173, EP-A 503 538;
MeLeu = N-methyl-L-leucine, D-Lac = D-lactic acid, D-PhLac =
D-phenyllactic acid

Claims (10)

claims
1. A compound of the general formula (I) in which R1, R4, R7 and R11 independently of one another represent hydrogen, straight-chain or branched alkyl, R2, R5, R8 and R11 independently of one another represent hydrogen, optionally substituted straight-chain or branched alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, arylalkyl, hetarylalkyl and also aryl or hetaryl, R10 and R11 together with the atoms to which they are attached represent an optionally substituted 5- or 6-membered ring which may optionally be interrupted by oxygen, sulfur, sulfoxy or sulfonyl, R6 and R12 independently of one another represent hydrogen, optionally substituted alkyl or arylalkyl, and also optionally substituted cycloalkylalkyl, R3 and R9 independently of one another represent hydrogen, optionally substituted straight-chain or branched alkyl, alkenyl, cycloalkyl, alkoxycarbonylalkyl, cycloalkylalkyl, arylalkyl, hetarylalkyl, aryl or hetaryl, and C=X1, C=X2, C=X3 and C=X4 independently of one another each represent one of the groups C=O, C=S or CH2 or a group C=N-A, where at least one of the groups C=X1, C=X2, C=X3 and C=X4 must represent C=N-A, in which A represents hydrogen, optionally substituted alkyl, alkenyl, alkinyl, alkylcarbonyl, alkylsulfonyl, and also cyano, nitro, carbamoyl, alkoxycarbonyl, formyl, -(C=NH)-NH2, -P(O)-O-alkyl, -P(S)-O-alkyl or optionally represents a radical A1 -Y-R13 (A1) in which Y represents oxygen, sulfur or -N-R14, R13 and R14 independently of one another represent hydrogen, optionally substituted straight-chain or branched, alkyl, alkenyl, alkinyl, cycloalkyl, cyclo-alkylalkyl, arylalkyl, hetarylalkyl, aryl or hetaryl and also represent formyl, alkoxydicarbonyl, alkylsulfonyl, haloalkoxy-alkylsulfonyl, alkoxycarbonyl, alkylaminocarbonyl, alkenyloxy-carbonyl, alkinyloxycarbonyl, aryloxyalkyl, hetarylcarbonyl, alkyl-carbonyl or optionally represent a radical from the group consisting of B1, B2, B3 and B4, in which Q represents optionally substituted straight-chain or branched alkyl, alkenyl, alkinyl, cycloalkyl, alkoxy, alkenyloxy, alkinyloxy, cycloalkoxy, aryloxy, arylalkoxy, hetaryloxy, hetarylalkoxy, alkylthio, alkenylthio, alkinylthio, cycloalkylthio, arylthio, arylalkylthio, hetaryl-thio, hetarylalkylthio, alkylamino, alkenylamino, alkinylamino, cycloalkylamino, arylamino, arylalkylamino, hetarylamino, hetaryl-alkylamino, dialkylamino, dialkenylamino, aryl, arylalkyl, hetaryl or hetarylalkyl, cyano, amino or an optionally substituted cyclic amino group which is attached via nitrogen, represents carboxyl, thiocarboxyl, sulfoxy, sulfonyl, -P(O)-O-alkyl, -P(S)-O-alkyl or -C=N-R15, R15 represents hydrogen, hydroxyl, alkoxy, alkylcarbonyl, alkoxy carbonyl, haloalkylcarbonyl, alkylsulfonyl, nitro or cyano, R16 represents hydrogen or alkyl, n represents 0, 1 or 2, Y1 represents oxygen or sulfur or -N-R17, R18 represents, if Y1 represents nitrogen, a cyclic amino group which is attached via this nitrogen atom, R17 and R18 independently of one another represent hydrogen, optionally substituted straight-chain or branched alkyl, alkenyl, alkinyl, cycloalkyl, cycloalkylalkyl, alkoxycarbonyl, aryl, arylalkyl, hetaryl or hetarylalkyl, or R17 and R18 together with the adjacent N atom represent an optionally substituted heterocyclic 4-, 5-, 6- or 7-membered ring system or represent an optionally substituted 7- to 10-membered bicyclic ring system which may optionally also be interrupted by oxygen, sulfur, sulfoxyl, sulfonyl, carbonyl, -N-O, -N=, -NR22 or by quaternary nitrogen, R19 and R20 independently of one another represent hydrogen, straight-chain or branched alkyl, alkenyl, cycloalkyl and also optionally substituted aryl, arylalkyl, hetaryl, hetarylalkyl, or R19 and R20 together represent an optionally substituted spirocyclic ring, R20 and R21 together with the atoms to which they are attached represent an optionally substituted 5-, 6- or 7-membered ring which may optionally be interrupted by oxygen, sulfur, sulfoxyl, sulfonyl, R21 represents hydrogen, optionally substituted straight-chain or branched alkyl, cycloalkyl, arylalkyl, hetarylalkyl, and also aryl or hetaryl, R22 represents hydrogen, optionally substituted straight-chain or branched alkyl, alkenyl, alkinyl, cycloalkyl, cycloalkylalkyl, alkoxycarbonyl, alkylcarbonyl, cycloalkylcarbonyl, cyano, arylalkyl, hetarylalkyl, and also aryl or hetaryl, R13 may also represent a protective group which can be removed selectively, or a polymeric support which is attached to Y via an anchor group which can be removed selectively, or a pure optical isomer, racemate or physiologically acceptable salt thereof.
2. A cycloiminodepsipeptide as claimed in claim 1 of the general formula (I) in which R1, R4, R7 and R10 represent straight-chain or branched C1-4-alkyl, in particular methyl, R2, R5, R8 and R11 independently of one another represent C1-4-alkyl, in particular isobutyl, R6 and R12 independently of one another represent optionally substituted C1-4-alkyl or aryl-C1-2-alkyl, in particular optionally substituted benzyl, R3 and R9 independently of one another represent optionally C1-4-alkyl, hetaryl-C1-2-alkyl, C1-C4-alkoxycarbonylmethyl, aryl-C1-2-alkyl, in particular optionally substituted benzyl, substituents that may be mentioned being hydrogen, halogen, cyano, carbamoyl, C1-4-alkyl, hydroxyl which carries a protective group or unprotected hydroxyl, C1-4-alkoxy, C1-4-alkoxy-C1-4-alkoxy, C2-4-alkenyloxy, hetaryl-C1-4-alkoxy, where the heterocycles for their part may be substituted, nitro, or a radical from the group consisting of R23R24N-C1-C6-alkoxy, R23R24N-C1-C8-alkyl, NR23R24 and -SO2-NR23R24, in which R23 and R24 independently of one another each represent hydrogen, C1-C6-alkyl, C1-C6-alkoxy-C1-C6-alkyl, C3-C7-cycloalkyl, C3-C7-cyclo-alkylamino-C1-C6-alkyl, wherein the cycloalkyl ring one or more carbon atoms may also be replaced by nitrogen, oxygen or sulfur atoms, hetaryl-C1-C4-alkyl or a protective group, or R23 and R24 together with the nitrogen atom to which they are attached represent hetaryl or heterocycloalkyl, in particular N-pyrrolidino, N-piperazino, N-morpholino, N-thiomorpholino, N-piperidino, N-imidazolo, 2-oxo-pyrrolidinyl, phthalimino or tetrahydrophthalimino, and (i) C=X1 represents a group C=N-A, C=X2, C=X3 and C=X4 represent C=O, C=S or CH2, or (iii) C=X3 represents a group C=N-A, C=X1, C=X2 and C=X4 represents C=O, C=S or CH2, or (iv) C=X1 and C=X3 represent a group C=N-A, C=X2 and C=X4 represent C=O, C=S or CH2, in which A represents hydrogen, optionally substituted C1-4-alkyl, C2-4-alkenyl, C2-4-alkinyl, C1-C4-alkylcarbonyl, C1-6-alkylsulfonyl and also cyano, nitro, carbamoyl, C2-6-alkoxycarbonyl, formyl, -(C=NH)-NH2, -P(O)-O-C1-3-alkyl, -P(S)-O-C1-3-alkyl or optionally represents a radical A1 -Y-R13 (A1) where Y represents oxygen or -N-R14, R13 and R14 independently of one another represent hydrogen, optionally substituted straight-chain or branched C1-8-alkyl, C2-8-alkenyl, C2-8-alkinyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-2-alkyl, aryl-C1-2-alkyl, hetaryl-C1-2-alkyl, aryl or hetaryl and also formyl, C1-C8-alkylsulfonyl, C1-C2-haloalkoxy-C1-2-alkylsulfonyl, C1-C8-alkylcarbonyl, C1-C8-alkoxycarbonyl, C1-C8-alkylaminocarbonyl, C2-C8-alkenyloxy-carbonyl, C2-C8-alkinyloxycarbonyl, aryloxy-C1-C2-alkyl, hetaryl-carbonyl, C1-4-alkoxydicarbonyl or optionally represent a radical from the group consisting of B1, B2, B3 and B4 <IMGs>

in which Q represents optionally substituted straight-chain or branched C1-8-alkyl, C2-8-alkenyl, C2-8-alkinyl, C3-7-cycloalkyl, C1-6-alkoxy, C2-6-alkenyloxy, C2-6-alkinyloxy, C3-7-cycloalkoxy, aryloxy, aryl-C1-2-alkoxy, hetaryloxy, hetaryl-C1-2-alkoxy, C1-6-alkylthio, C2-6-alkenylthio, C2-6-alkinylthio, C3-7-cycloalkyl-thio, arylthio, aryl-C1-2-alkylthio, hetarylthio, hetaryl-C1-2-alkylthio, C1-6-alkylamino, C2-6-alkenylamino, C2-6-alkinylamino, C3-6-cyclo-alkylamino, arylamino, aryl-C1-2-alkylamino, hetarylamino, hetaryl-C1-2-alkylamino, di-C1-4-alkylamino, di-C2-4-alkenylamino, aryl, aryl- C1-2-alkyl, hetaryl, hetaryl-C1-C2-alkyl and also cyano, amino or an optionally substituted cyclic amino group which is attached via nitrogen, represents thiocarboxyl or carboxyl, R15 represents hydrogen, hydroxyl, C1-4-alkoxy, C1-4-alkylcarbonyl, C1-4-alkoxycarbonyl, halogeno-C1-4-alkylcarbonyl, C1-4-alkylsulfonyl, nitro or cyano, R16 represents hydrogen or C1-4-alkyl, n represents 0, 1 or 2, Y1 represents oxygen, sulfur or -N-R17, R18 represents, if Y1 represents nitrogen, a cyclic amino group which is attached via this nitrogen atom, R17 and R18 independently of one another represent hydrogen, optionally substituted straight-chain or branched C1-6-alkyl, C2-6-alkenyl, C2-6-alkinyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-6-alkyl, C1-6-alkoxy-carbonyl, aryl, aryl-C1-2-alkyl, hetaryl, hetaryl-C1-2-alkyl, or R17 and R18 together with the adjacent N atom represent an optionally substituted heterocyclic 4-, 5-, 6- or 7-membered ring system or represent an optionally 7- to 10-membered bicyclic ring system which may optionally also be interrupted by oxygen, sulfur, sulfoxyl, sulfonyl, carbonyl, -N-O, -N=, -NR22 or by quaternary nitrogen, R19 and R20 independently of one another represent hydrogen, optionally substituted straight-chain or branched C1-6-alkyl, C2-6-alkenyl, C3-7-cycloalkyl and also optionally substituted aryl, aryl-C1-2-alkyl, hetaryl, hetaryl-C1-2-alkyl, or R19 and R20 together represent an optionally substituted spirocyclic ring, R20 and R21 together with the atoms to which they are attached represent an optionally substituted 5-6- or 7-membered ring which may optionally be interrupted by oxygen, sulfur, sulfoxyl, sulfonyl, R21 represents hydrogen, optionally substituted straight-chain or branched C1-6-alkyl, C3-7-cycloalkyl, aryl-C1-2-alkyl, hetaryl-C1-2-alkyl, and also aryl or hetaryl, R22 represents hydrogen, optionally substituted straight-chain or branched C1-6-alkyl, C2-6-alkenyl, C2-6-alkinyl, C3-7-cycloalkyl, C3-7-cycloalkyl-C1-6-alkyl, C1-6-alkoxycarbonyl, C1-6-alkylcarbonyl, C3-7-cycloalkyl-carbonyl, cyano, aryl-C1-2-alkyl, hetaryl-C1-2-alkyl, and also aryl or hetaryl, R13 also represents a protective group which can be removed selectively, for example allyl, allyloxycarbonyl (Alloc), benzyl (Bn), benzyloxy-carbonyl (Z), tert-butyloxycarbonyl (Boc), tetrahydropyran-2-yl (THP) or fluorenylmethoxycarbonyl (Fmoc) and also represents a polymeric support which is attached to Y via an anchor group which can be removed selectively, or an optical isomer, racemate or physiologically acceptable salt thereof.
3. A process 1 for preparing the novel compounds of the general formula (I) as claimed in claim 1 in which R1 to R12 and the groups C=X1 to C=X4 have the meanings given in claim 1, characterized in that cyclothiodepsipeptides of the general formula ( I ) and salts thereof, in which R1 to R12 have the meanings given in claim 1, and C=X1, C=X2, C=X3 and C=X4 independently of one another represent C=O, C=S or CH2, where at least one of the groups C=X1, C=X2, C=X3 and C=X4 has to represent a C=S group, are reacted with amino compounds of the general formula (II) H2N-A (II) in which A has the meanings given in claim 1 in the presence of suitable metal salts or metal oxides, in particular mercury (II) acetate, mercury(II) chloride or mercury(II) oxide, in the presence of a basic reaction auxiliary and in the presence of a suitable diluent.
4. A process for preparing the compounds of the formula (Ia) and salts thereof, characterized in that a) the cyclothiodepsipeptides of the general formula (Ib) or salts thereof in which R1 to R12 have the meanings given in claim 1 are reacted with amino compounds of the general formula (II) H2N-A (II) in which A has the meanings given in claim 1 in the presence of suitable metal salts or metal oxides, in particular mercury (II) acetate, mercury (II) chloride or mercury(II) oxide, and in the presence of a basic reaction auxiliary and in the presence of a suitable diluent, or b) for preparing the novel cycloiminodepsipeptides of the general formula (Ia) and salts thereof, in which R1 to R12 have the meanings mentioned in claim 1, A represents a radical -Y-R13 (A1), in which Y has the meaning given in claim 1, R13 represents radicals from the group consisting of B1 to B3 <IMGs>

in which Q, Y1, n, R16, and R18-R20 have the meanings given in claim 1, compounds of the general formula (Ic) and salts thereof, in which Y and R1 to R12 have the meanings given in claim 1 are reacted with compounds of the general formula ( IIIa-c ) <IMGs>

in which Q, Y1, n, R16, and R18-R20 have the meanings given in claim 1, W represents a suitable leaving group, such as, for example, halogen, if appropriate in the presence of a catalyst, if appropriate in the presence of a basic reaction auxiliary and if appropriate in the presence of diluents, or c) for preparing compounds of the general formula (Ia) and salts thereof, in which A represents a radical -Y-R13 (A1) in which Y has the meanings given in claim 1, R13 represents radicals from the group consisting of B1 and B3 <IMGs>

in which Q, Y1, n, R18-R20 have the meanings given in claim 1, n represents 0, and the group represents carboxyl, the compounds of the general formula (Ic) and salts thereof in which Y and R1 to R12 have the meanings given in claim 1 are reacted with a carboxylic anhydride of the general formula (IV) (Q-CO)2O (N) in which Q has the meaning given in claim 1 or represents the radical in which Y1, R18-R20 have the meaning given in claim 1, if appropriate in the presence of a catalyst, if appropriate in the presence of a basic reaction auxiliary and if appropriate in the presence of diluents, or d) by reacting compounds of the general formula (Ic) a) with amino acid derivatives of the general formula (V) in which Q, and R19 to R21 have the meaning given in claim 1 if appropriate in the presence of coupling agents and if appropriate in the presence of a basic reaction auxiliary and also, if appropriate, in the presence of diluents, or .beta.) with compounds of the general formulae (VI) and (VII) R15-N=C=Y (VI) in which Y and R15 have the meaning given in claim 1, if appropriate in the presence of a basic reaction auxiliary or a catalyst, if appropriate in the presence of diluents.
5. A process for preparing compounds of the general formula (Ic) and salts thereof, in which Y and R1 to R12 have the meanings given in claim 1, characterized in that a) from the compounds of the general formula (Ia) and salts thereof, in which R1 to R12 have the meanings given in claim 1, A represents a radical -Y-R13 (A1), in which Y represents oxygen or -N-H, R13 represents a protective group which can be removed selectively, for example, allyl, allyloxy-carbonyl (Alloc), benzyl (Bn), benzyloxycarbonyl (Z), tert-butyloxycarbonyl (Boc), tetrahydropyran-2-yl (THP) or in fluorenylmethoxycarbonyl (Fmoc), the radical R13 is selectively removed, depending on the removable protective group either in the presence of a hydrogenation catalyst, in the presence of a protic acid or a basic reaction auxiliary and in the presence of a diluent, or b) from the compounds of the general formula ( Ia ), attached to a polymeric support, and salts thereof, in which R1 to R12 have the meanings given in claim 1, A represents a radical -Y-R13 (A1) in which Y represents oxygen or -N-H, R13 represents a selectively removable anchor group on a polymeric support, the compounds of the formula (Ic) are released by selective removal of the anchor group from the polymeric support R13 in the presence of a suitable catalyst or in the presence of a protic acid and in the presence of a diluent.
6. A composition, characterized in that it comprises at least one compound of the formula (I) as claimed in claim 1.
7. The use of compounds of the formula (I) as claimed in claim 1 for controlling endoparasites.
8. A method for controlling endoparasites, characterized in that compounds of the formula (I) as claimed in claim 1 are allowed to act on endoparasites and/or their habitat.
9. A process for preparing compositions against endoparasites, characterized in that compounds of the formula (I) as claimed in claim 1 are mixed with extenders and/or surfactants.
10. The use of compounds of the formula (I) as claimed in claim 1 for preparing compositions against endoparasites.
CA002374632A 1999-06-11 2000-05-30 Cyclo-imino depsipeptides and their utilization in controlling endoparasites Abandoned CA2374632A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19926620.4 1999-06-11
DE19926620A DE19926620A1 (en) 1999-06-11 1999-06-11 New cycloiminodepsipeptides, processes for their preparation and their use in combating endoparasites
PCT/EP2000/004935 WO2000076985A1 (en) 1999-06-11 2000-05-30 Cyclo-imino depsipeptides and their utilization in controlling endoparasites

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CN (1) CN1355794A (en)
AU (1) AU768501B2 (en)
BR (1) BR0011498A (en)
CA (1) CA2374632A1 (en)
DE (1) DE19926620A1 (en)
HK (1) HK1047589A1 (en)
HU (1) HUP0201592A2 (en)
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JP4902519B2 (en) * 2007-12-21 2012-03-21 大塚化学株式会社 Immobilized catalyst
MX2021001566A (en) * 2015-05-20 2022-09-12 Boehringer Ingelheim Animal Health Usa Inc Anthelmintic depsipeptide compounds.

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DE4317432A1 (en) * 1993-05-26 1994-12-01 Bayer Ag Octacyclodepsipeptides with endoparasiticidal activity
DE4317457A1 (en) * 1993-05-26 1994-12-01 Bayer Ag Octacyclodepsipeptides with endoparasiticidal activity
DE19713626A1 (en) * 1997-04-02 1998-10-08 Bayer Ag New thiodepsipeptides to control endoparasites and a simple process for their preparation

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WO2000076985A1 (en) 2000-12-21
CN1355794A (en) 2002-06-26
ZA200109179B (en) 2003-01-29
AU768501B2 (en) 2003-12-11
HK1047589A1 (en) 2003-02-28
HUP0201592A2 (en) 2002-08-28
EP1192142A1 (en) 2002-04-03
AU5218000A (en) 2001-01-02
JP2003502318A (en) 2003-01-21
DE19926620A1 (en) 2000-12-14

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