The muraymycins, a family of nucleoside-lipopeptide antibiotics, were purified from the extract of Streptomyces sp. LL-AA896. The antibiotics were purified by chromatographic methods and characterized by NMR spectroscopy, degradation studies, and mass spectrometry. The structures of 19 compounds were established. The muraymycins constitute a new antibiotic family whose core structure contains a glycosylated uronic acid derivative joined by an aminopropane group to a hexahydro-2-imino-4-pyrimidylglycyl residue (epicapreomycidine) containing dipeptide that is further extended by a urea-valine moiety. Members of this family show broad-spectrum in vitro antimicrobial activity against a variety of clinical isolates (MIC 2 to >64 mug/mL). The muraymycins inhibited peptidoglycan biosynthesis. The fatty acid substituent and the presence or absence of the amino sugar play important roles in biological activity. One of the most active compounds, muraymycin A1, demonstrated protection in vivo against Staphylococcus aureus infection in mice (ED50 1.1 mg/kg).

360ChemInform Abstract The structure of the title compound, the major component of the calichemicin complex (isolated from Micromonospora echinospora ssp. calichensis and known as LL-E33288 antibiotics) is investigated in part by chemical (derivatization, degradations etc.) and physical methods. It can be shown that the title compound consists of four glycosidic units, a hexasubstituted benzene moiety and an undefined C18H16NO4S3 unit. The exact configuration of the ethylamino sugar is unknown. In the following paper the structure of the undefined aglycone is reported.

Fluorescent bisretinoids, such as A2E and all-trans-retinal dimer, form as a by-product of vitamin A cycling in retina and accumulate in retinal pigment epithelial (RPE) cells as lipofuscin pigments. These pigments are implicated in pathological mechanisms involved in several vision-threatening diseases including age-related macular degeneration. Efforts to understand damaging events initiated by these bisretinoids have revealed that photoexcitation of A2E by wavelengths in the visible spectrum leads to singlet oxygen production and photooxidation of A2E. Here we have employed liquid chromatography coupled to electrospray ionization mass spectrometry together with tandem mass spectrometry (MS/MS), to demonstrate that A2E also undergoes photooxidation-induced degradation and we have elucidated the structures of some of the aldehyde-bearing cleavage products. Studies in which A2E was incubated with a singlet oxygen generator yielded results consistent with a mechanism involving bisretinoid photocleavage at sites of singlet molecular oxygen addition. We provide evidence that one of the products released by A2E photodegradation is methylglyoxal, a low molecular weight reactive dicarbonyl with the capacity to form advanced glycation end products. Methylglyoxal is already known to be generated by carbohydrate and lipid oxidation; this is the first report of its production via bisretinoid photocleavage. It is significant that AGE-modified proteins are detected in deposits (drusen) that accumulate below RPE cells in vivo; drusen have been linked to age-related macular degeneration pathogenesis. Whereas various processes play a role in drusen formation, these findings are indicative of a contribution from lipofuscin photooxidation in RPE.advanced glycation end products | lipofuscin | photofragmentation | photooxidation | retinal pigment epithelial cells F luorescent bisretinoid pigments are amassed as lipofuscin in retinal pigment epithelial (RPE) cells in association with aging although individuals vary with respect to the extent of accumulation (1). The excessive deposition of these compounds in RPE cells is also considered to lead to retinal degeneration in early onset blinding disorders associated with mutations in the genes encoding ABCA4 (ATP-binding cassette subfamily A member 4) (2, 3), ELOVL4 (4), and BEST-1 (5). Moreover, the deposition of these pigments likely also contributes to the etiology of agerelated macular degeneration (AMD) (6, 7). Whereas these bisretinoids constitute a complex mixture, all appear to originate from reactions of all-trans-retinal and some have been identified, including A2E (Fig. 1) and its isomers (8); A2-dihydropyridinephosphatidylethanolamine (A2-DHP-PE) and A2-dihydropyridine-ethanolamine (A2-DHP-E) (9); and all-trans-retinal dimer, all-trans-retinal dimer-phosphatidylethanolamine (all-transretinal dimer-PE), and all-trans-retinal dimer-ethanolamine (alltrans-retinal dimer-E) (10, 11). Structural features common to all of these pigments are the alternating single and double carbon...

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361ChemInform Abstract Further chemical and physical investigations on the structure of the title compound, in addition to the results of the preceding paper, establish its complete structure as (I).