In an analytical study of microbial broths the actinomycete strain sp.

In an analytical study of microbial broths the actinomycete strain sp. term_id :”239938945″}}P07101 was found to produce three new congeners which were designated hazimycins B (1) C (2) and D (3) together with the previously reported hazimycin (renamed hazimycin A). {Only hazimycin A exhibited moderate antimicrobial activities against Gram-positive bacteria and yeast.|Only hazimycin A exhibited moderate antimicrobial activities against Gram-positive yeast and bacteria.} These results indicated that the presence of two isonitrile groups in the hazimycin structure is essential for antimicrobial activity. 1 Our research group has focused on discovering novel compounds from microbial metabolites1 2 3 4 Compounds were screened from our original culture collection using LC–UV and LC–MS/MS instruments. During this chemical screening program the actinomycete strain sp. {“type”:”entrez-protein” attrs :{“text”:”P07101″ term_id :”239938945″}}P07101 was found to produce unidentified compounds. Novel hazimycins hazimycins B (1) C (2) and D (3) were recently isolated from the fermentation broth along with the known antibiotic hazimycin5 (renamed hazimycin A (4) Fig. 1). {These new congeners possessed a diaryl skeleton that contained isonitrile and nitrile groups which are rare among microbial metabolites.|These new congeners possessed a LY315920 diaryl skeleton that contained nitrile and isonitrile groups which are rare among microbial metabolites.} The isolation structure elucidation and biological activities of 1–3 have been described in the present study. Figure 1 Structures of 1–4. 2 and discussion 2.1 Structure elucidation of LY315920 1–3 The physicochemical properties of compounds 1–3 are summarized in Table 1. {Compounds 1–3 showed UV absorption between approximately 212?|Compounds 1–3 showed UV absorption between 212 approximately?}nm and 289?nm which was identical to that of 4. The IR absorption at 2150–2300?cm–1 suggested the presence of isonitrile and/or nitrile groups in their structures. {These results indicated that the basic skeleton of 1–3 was similar to that of 4.|These total results indicated that the basic skeleton of 1–3 was similar LY315920 to that of 4.} Table 1 Physicochemical properties of 1–3. The structure of 1 was elucidated from various spectral data including NMR experiments. The molecular formula of 1 was determined to be LY315920 C20H20N4O5 based on HR-ESI-MS measurements which indicated that the molecular formula of 1 has one oxygen atom and two hydrogen atoms more than that of 4. The 13C-NMR spectrum showed 20 resolved signals which were classified into two carbon two 7.92) and amide proton signal (8.17) were observed in 1 but were absent in 4 Rabbit Polyclonal to HNRNPUL2. which indicated that one of two isonitrile groups was converted to an NH-formyl group in 1. Cross peaks were observed from H-2″ (4.43) to C-4″ (160.9) as well as from NH-2″ (8.17) to C-4″ in the 13C–1H heteronuclear multiple-bond correlation (HMBC) experiments (Fig. 2A). The structure satisfied the unsaturation number UV spectra and molecular formula. {These results indicated that compound LY315920 1 was a 2″-NH-formyl hazimycin as shown in Fig.|These total results indicated that compound LY315920 1 was a 2″-NH-formyl hazimycin as shown in Fig.} 1. Figure 2 Key HMBCs of 1 and 2. Table 2 1 and 13C NMR chemical shifts of 1–3. The molecular formula of 2 was identical to that of 1. {However two proton signals of an NH-formyl group (8.|Two proton signals of an NH-formyl group (8 However.}06 and 8.86) were newly observed and one of the amide proton signals of the two carboxamide groups (7.48 and 7.71) disappeared in the 1H NMR spectrum of 2. Furthermore a new carbon signal (119.0) was observed in place of one of the two carboxamide carbon signals (167.1) in the 13C NMR spectrum of 2. These results indicated the formylation of another isonitrile group of 1 and the conversion of one of the two carboxamide groups of 1 to a nitrile group in 2. The position of the nitrile group was confirmed by 13C–1H HMBC experiments (Fig. 2B): cross peaks were observed from H-2 (4.98) to C-1 (119.0) and C-4 (161.1). Thus compound 2 was elucidated to be 2 2 and 2-nitrle hazimycin (Fig. 1). As listed in Table 1 the molecular formula of 3 has one oxygen atom and two hydrogen atoms fewer than that of 2. Its 1H-NMR spectrum revealed homodimer-type proton signals and was almost identical to that of 2 except for the disappearance of the amide proton signals of the carboxamide groups (7.04 and 7.48) in 3. Furthermore the presence of a nitrile carbon signal (119.0) was confirmed as well as 2 in the 13C-NMR spectrum which indicated that another carboxamide group of 2 was converted to a nitrile group in 3. Finally cross peaks were observed from H-2″ (4.90) to C1″ (119.0) and C4″ (161.1) as well as from NH-2″ (8.86) to C4″ in the 13C–1H HMBC experiments. Thus compound 3 was elucidated to be a 2 2 and 2 2 hazimycin (Fig. 1) Regarding the absolute stereochemistry of the novel hazimycin analogs dityrosine was prepared by hydrolyzing 4 under acidic conditions because its optical rotation has already been accurately described in.