UK-2 A , B , C and D , Novel Antifungal Antibiotics from Streptomyces sp . 517-02 VI ( 1 ) . Structure-Activity Relationships of UK-2 A

compounds), which have similarity to antimycin A3 (AA) in structure and inhibitory activities towards electron transport at complex III in mitochondria.1^ However, UK-2 compounds inhibited the growth of Rhizopus formosaensis IFO 4732 at 0.0125 /ig/ml, while AA showed no effect on it up to lOO^g/ml. In contrast, UK-2 compounds were less active than AA against mouse leukemia P388, mouse melanoma B16, human oral epidermoid carcinoma KB and human colon adenocarcinoma COLO201cells. In our continuing studies on UK-2A (main component of UK-2 compounds),4~7) we have been much interested in establishing structure-activity relationships of UK-2A. Herein, we like to report our preliminary studies on the synthesis of UK-2Aanalogues where the nine-memberedilactone residue was replaced by several alkyl or isoprenyl moieties, and their biological effects. The structures of UK-2Aand AAderivatives prepared here are represented in Fig. 1. 3-Hydroxy-4-methoxypyridine-2-carboxylic acid was prepared from commercially available 3-hydroxypyridine in the literature procedure.8) Prenyl amine and farnesyl amine were prepared according to the Gabriel method from the corresponding bromide.9) Amide formation was achieved in chloroform with l-ethyl-3-(3-dimethyl-aminopropyl)-