Eli Lilly and Company

Bernard J Abbott

David S Fukuda

Manuel Debono

Robert A Archer

Dennis R Berry

John G Whitney

A-21978C cyclic peptide derivatives of the formula ##STR1## in which R, R.sup.1 and R.sup.2 are, independently, hydrogen, C.sub.4 -C.sub.14 -alkyl, optionally substituted C.sub.2 -C.sub.19 -alkanoyl, C.sub.5 -C.sub.19 -alkenoyl or an amino-protecting group; R.sup.3, R.sup.4 and R.sup.5 are hydrogen or (i) R.sup.3 and R.sup.1 and/or (ii) R.sup.4 and R and/or (iii) R.sup.5 and R.sup.2, taken together, may represent a C.sub.4 -C.sub.14 alkylidene group; provided that (1) at least one of R, R.sup.1 or R.sup.2 must be other than hydrogen or an amino-protecting group, (2) at least one of R.sup.1 or R.sup.2 must be hydrogen or an amino-protecting group, (3) the R, R.sup.1 and R.sup.2 groups must together contain at least four carbon atoms, and (4) when R.sup.1 and R.sup.2 are both selected from hydrogen or an amino-protecting group, R cannot be 8-methyldecanoyl, 10-methyldodecanoyl, 10-methylundecanoyl, the mixed C.sub.10 -alkanoyl group of A-21978C.sub.0 or the specific C.sub.12 -alkanoyl groups of A-21978C factors C.sub.4 and C.sub.5 ; and the salts thereof.

Derivatives of A-21978C cyclic peptides

A-21978C cyclic peptides of the formula ##STR1## wherein R is selected from the group consisting of hydrogen, an amino-protecting group , 8-methyldecanoyl, 10-methylundecanoyl, 10-methyldodecanoyl, the specific C.sub.10 -alkanoyl group of A-21978C factor C.sub.0 and the specific C.sub.12 -alkanoyl groups of A-21978C factors C.sub.4 and C.sub.5 ; R.sup.1 and R.sup.2 are, independently, hydrogen or an amino-protecting group, and salts thereof, are prepared by enzymatic deacylation of an antibiotic selected from A-21978C complex, A-21978C factors C.sub.0, C.sub.1, C.sub.2, C.sub.3, C.sub.4 and C.sub.5 and blocked A-21978C complex and factors C.sub.0, C.sub.1, C.sub.2, C.sub.3, C.sub.4 and C.sub.5, using an enzyme produced by the Actinoplanaceae, preferably by Actinoplanes utahensis. The A-21978C cyclic peptides and salts thereof are useful intermediates to prepare new semi-synthetic antibacterial agents.

A-21978C cyclic peptides

A-21978C cyclic peptides of the formula ##STR1## wherein R is selected from the group consisting of hydrogen, an amino-protecting group, 8-methyldecanoyl, 10-methylundecanoyl, 10-methyldodecanoyl, the specific C.sub.10 -alkanoyl group of A-21978C factor C.sub.0 and the specific C.sub.12 -alkanoyl groups of A-21978C factors C.sub.4 and C.sub.5 ; R.sup.1 and R.sup.2 are, independently, hydrogen or an amino-protecting group, and salts thereof, are prepared by enzymatic deacylation of an antibiotic selected from A-21978C complex, A-21978C factors C.sub.0, C.sub.1, C.sub.2, C.sub.3, C.sub.4 amd C.sub.5 and blocked A-21978C complex and factors C.sub.0, C.sub.1, C.sub.2, C.sub.3, C.sub.4 and C.sub.5, using an enzyme produced by the Actinoplanaceae, preferably by Actinoplanes utahensis. The A-21978C cyclic peptides and salts thereof are useful intermediates to prepare new semi-synthetic antibacterial agents.

Compounds of the formula ##STR1## wherein R.sup.1 is C.sub.6 -C.sub.24 alkyl or C.sub.6 -C.sub.24 alkenyl, have antifungal activity.

Derivatives of A-30912B nucleus

Derivatives of A-30912A nucleus

Derivatives of A-30912D nucleus

Compounds of the formula ##STR1## wherein R.sup.1 is C.sub.6 -C.sub.24 alkyl or C.sub.6 -C.sub.24 alkenyl and R.sup.2 is C.sub.1 -C.sub.6 alkyl, have antifungal activity.

Derivatives of A-30912H nucleus

The microorganism Streptomyces capillispira, NRRL 12279, produces an enzyme which deesterifies cephalosporin methyl esters.

Enzymatic deesterification of cephalosporin methyl esters

S 31794/F-1 nucleus, which is prepared by enzymatic deacylation of antibiotic S 31794/F-1 using an enzyme produced by the Actinoplanaceae, preferably by Actinoplanes utahensis. S 31794/F-1 nucleus and salts thereof are useful intermediates for the preparation of new semi-synthetic antifungal agents.

S 31794/F-1 Nucleus

A-30912B nucleus, which is prepared by enzymatic deacylation of an antibiotic selected from A-30912 factor B and tetrahydro-A-30912B using an enzyme produced by the Actinoplanaceae, preferably by Actinoplanes utahensis. A-30912B nucleus and salts thereof are useful intermediates to prepare new semisynthetic antifungal agents.

A-30912B Nucleus

A-30912D nucleus, which is prepared by enzymatic deacylation of an antibiotic selected from A-30912 factor D and tetrahydro-A-30912D using an enzyme produced by the Actinoplanaceae, preferably by Actinoplanes utahensis. A-30912D nucleus and salts thereof are useful intermediates to prepare new semi-synthetic antifungal agents.

A-30912D Nucleus

A-30912A nucleus, which is prepared by enzymatic deacylation of an antibiotic selected from A-30912 factor A, tetrahydro-A-30912A, and aculeacin A using an enzyme produced by the Actinoplanaceae, preferably by Actinoplanes utahensis. A-30912A nucleus and salts thereof are useful intermediates to prepare new semi-synthetic antifungal agents.

A-30912A Nucleus

A-30912H-type nuclei of formula 1, which are prepared by enzymatic deacylation of an antibiotic having formula 2 using an enzyme produced by the Actinoplanaceae, preferably by Actinoplanes utahensis. A-30912H-type nuclei and salts thereof are useful intermediates for preparing new semi-synthetic anti-fungal agents.

A-30912H Nuclei

Derivatives of S31794/F-1 nucleus

Cultivation of Streptomyces chartreusis NRRL 11407 in the presence of antibiotic A23187 methyl ester produces 16-hydroxy A23187 methyl ester, 16-hydroxy-N-demethyl A23187 methyl ester, and N-demethyl A23187 methyl ester. Hydrolysis of the products affords the corresponding free acids which form dimeric complexes with divalent cations.

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Greenwood, IN, United States of America

Bernard J Abbott