title: Synthesis and antifungal activities of pradimicin derivatives, modification at C4'-position.
abstract: The 4'-N-alkyl(1 approximately 10) and 4'-N-acyl derivatives (11 approximately 21) of pradimicins (PRMs) were synthesized by trimethylsilylation of PRMs A, C and FA-1 followed by condensation with appropriate alkylating and acylating agents. The 4'-hydroxy derivatives (23 and 24) were synthesized from PRM FA-2 in a 3-step sequence. Among these compounds, the 4'-N-carboxyl substituted alkyl (1, 5, 8 and 10), 4'-N-formyl (11) and 4'-axial-hydroxy (23) derivatives retained the antifungal activity of the parent compounds and showed great improvement in water solubility.
authors.affiliation: Bristol-Myers Squibb Research Institute, Bristol-Myers Squibb K.K., Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kamachi
authors.forename: S
authors.initials: S
authors.lastname: Iimura
authors.forename: S
authors.initials: S
authors.lastname: Okuyama
authors.forename: H
authors.initials: H
authors.lastname: Hoshi
authors.forename: S
authors.initials: S
authors.lastname: Tamura
authors.forename: M
authors.initials: M
authors.lastname: Shinoda
authors.forename: K
authors.initials: K
authors.lastname: Saitoh
authors.forename: M
authors.initials: M
authors.lastname: Konishi
authors.forename: T
authors.initials: T
authors.lastname: Oki
mesh_terms: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000737:chemistry; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D012995:Solubility; D013329:Structure-Activity Relationship; D000095643:Pradimicins and Benanomicins
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; C058036:pradimicin A; D000095643:Pradimicins and Benanomicins