Design of new pamamycin derivatives that show aerial mycelium-inducing or growth inhibition activity alone

1.去N-甲基帕霉素的分离、结构鉴定及生物活性研究帕霉素粗品在薄层层析中于Rf0.30处出现一个新的Dragendorff反应阳性斑点。该馏分经硅胶柱、ODS-和NH_2-HPLC纯化，得到三个新化合物。用甲硫氨酸-甲基-d_3饲养培养法制备的标记物，经质谱鉴定，其结构为去N-甲基帕霉素。去N-甲基帕霉素的气生菌丝诱导活性比相同烷基取代的帕霉素强，而生长抑制活性比相应的帕霉素弱。2.寻找N，N-去二甲基帕霉素为了寻找推测的生物合成前体N，N-去二甲基帕霉素，我们在甲基化抑制剂存在下培养了白黑链霉菌。结果，在DL-乙醇喂养培养物的提取物中发现了它。3.长烷基侧链帕霉素同系物的分离链霉菌HKI-0118能产生新的长烷基侧链帕霉素同系物，但尚未分离得到。我们用两个串联的NH_2-HPLC柱成功地分离了这些同系物。

1.Isolation, structure elucidation and biological activity of de-N-methylpamamycins A crude pamamycin fraction showed a new Dragendorff reaction-positive spot at Rf 0.30 on TLC analysis. This fraction was purified by silica gel column and ODS- and NH_2-HPLCs giving three new compounds. Their structures were determined as de-N-methylpamamycins by MS spectrometry with the aid of labeled compounds prepared in a methionine-methyl-d_3 feeding culture. De-N-methylpamamycins had stronger aerial mycelium-inducing activity and weaker growth-inhibition activity than the corresponding pamamycin with the same alkyl group arrangement.2.Search for N,N-didemethylpamamycins To search the presumed biosynthetic precursor, N,N-didemethyl- pamamycin, we cultured Streptomyces alboniger in the presence of methylation inhibitors. As a result, it was found in the extract of DL-ethionine feeding culture. Further investigation on the time of application and dose of ethionine will improve the yield.3.Isolation of pamamycin homologues with long alkyl side chain Streptomyces sp. HKI-0118 is reported to produce new pamamycin homologues with long alkyl side chain, but their isolation is not achieved. We succeeded in the isolation of these homologues by two NH_2-HPLC columns connected in series.