Synthesis and antifungal activities of pradimicin derivatives, modification at C4'-position.
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.
Kamachi
H
H
Bristol-Myers Squibb Research Institute, Bristol-Myers Squibb K.K., Tokyo, Japan.
Iimura
S
S
Okuyama
S
S
Hoshi
H
H
Tamura
S
S
Shinoda
M
M
Saitoh
K
K
Konishi
M
M
Oki
T
T
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
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; C058036:pradimicin A; D000095643:Pradimicins and Benanomicins