The structure and absolute configuration of the 18-membered macrolide lactone antibiotic X-4357B (concanamycin A).

Sir: The structure of the first l8-membered lactone, borrelidin, was described in 1967 by KELLERSCHIERLEIN1). In recent years, four more antibiotics have been added to this class. Concanamycins A, B and C2.3), produced by Streptomyces diastatochromogenes S45, inhibit the proliferation of mouse splenic lymphocytes stimulated by concanavalin A. The fourth antibiotic, virustomycin A4,5) also produced by a Streptomyces sp. (AM-2604A), is active against trichomonads and both DNA and RNA viruses. In 1978, a new antibiotic X-4357B, was reported in the patent literature6) to possess fungicidal, larvicidal and cytotoxic activities. In this communication, the structure determination of this 18-membered macrolide antibiotic by X-ray analysis of its diacetate derivative is described. The molecular formula of antibiotic X-4357B (1a) was deduced by microanalysis and fastatom-bombardment mass spectrometry to be C46H75NO14 (866.12). Although the antibiotic crystallized from methylene chloride ethanol, the crystals were not suitable for X-ray analysis. Conversion of antibiotic X-4357B to a diacetate (1b) which crystallized from ether hexane, yielded acceptable crystals for X-ray analysis. The diacetate (C50H7,NO16) has amp 169-171°C. The crystal data of lb are listed in Table 1*. The intensity data were measured on a HilgerWatts diffractometer (Ni-filtered CuKa radiation, 0-20 scans, pulse-height discrimination). The size of the crystal used for data collection was approximately 0.30 x 0.35 x 0.40 mm ; the data were not corrected for absorption. Of the 5,778 accessible reflections for 0<76°, 5,033 were considered to be observed [I > 3.0a(I)]. The structure of lb was solved by a multiplesolution procedure and was refined by block-diagonal least squares in which the matrix was partitioned into two blocks. Seven reflections which were strongly affected by extinction were excluded from the final refinement and difference map. In the final refinement, anisotropic thermal parameters were used for the non-hydrogen atoms and isotropic temperature factors were used for the hydrogen atoms. The hydrogen atoms were included in the structure factor calculations but their parameters were not refined. The final discrepancy indices are R=0.040 and wR= 0.049 for the remaining 5,026 observed reflections. The final difference map has no peaks greater than ±0.2 eA-3. Stereoscopic pictures of antibiotic X-4357B diacetate (1b) are shown in both the ball-andstick type presentation (Fig. 1) and as a spacefilling model (Fig. 2). The macrocyclic ring Table 1. Crystal data for 1b.