Depsipeptide antibiotics

Studies to elucidate the mode of bacteriostatic property of xanthostatin (XS), a novel depsipeptide antibiotic with an A/-acetylglydne side chain and selective antimicrobial activity against Xanthomonas spp., were carried ont by Kim and coworkers [80]. Two biotransformed XSs were isolated by the treatment of XS with the cell... 

Finally, several naturally occurring depsipeptide antibiotics containing the 2,3,4,5-tetrahydropyridazine or the hexahydropyridazine system have to be mentioned. In Japan, antrimycin (132, R = Me) has been isolated from Strepto-myces xanthocidicus MG125-CF1, which in vitro shows antibacterial activity (Mycobacterium smegmatis MIC 12.5 /rg/ml Mycobacterium tuberculosis MIC 50 /rg/ml) [366]. 

This method was used widely and successively in the synthesis of cyclic depsipeptide antibiotics and natural metabolites such as sporidesmolids I-IV,126-291 angolide,13(11 enniatins A... 

The cryptophycins (e.g. 16) form a group of depsipeptide antibiotics with a (R)-/7-AiB (R)-2 or / -Ala 1 substructure. They have already been isolated from cyanobacteria (Nostoc sp., see below) [47] arenastatin A 17 has been isolated from a marine sponge [42]. The cryptophycins are new lead structures within cancer drug research for their potent tumor-selective cytotoxicity [92]. The synthetic analog cryptophycin-52 (= 6-methylcryptophycin-l, LY-355703, 18) has reached clinical phase II trials [93]. 

T., and Ueda, K. (1996) Aureobasidin A, an antifungal cyclic depsipeptide antibiotic, is a substrate for both human MDRl and MDR2/P-glycoproteins. FEBS Letters, 399 (1-2), 29-32. 

Hamill RL, Higgens CE, Boaz HE, Gorman M. The structure of beauvericin, a new depsipeptide antibiotic toxic to Artemia salina. Tetrahedron Lett 4255-4258, 1969. 

Enopeptins A (62) and B (63) belong to a novel type of depsipeptide antibiotics isolated from a culture broth of Streptomyces sp. RK-1051 [127]. These antibiotics showed antibacteriophage activity in the assay system using actinophage B1 and Streptomyces griseus [127]. These compounds contain a phenylalanyl cyclopeptolide connected to a dodecapentaenedioic acid residue [128]. In contrast to the proline unit in (63), rratts-4-methylproline is found in (62). 

Kajimura, Y. and Kaneda, M. (1996) Fusaricidin A, a new depsipeptide antibiotic produced by Bacilluspolymyxa KT-8 Taxonomy, fermentation, isolation, stmcture elucidation and biological activity. The Journal of Antibiotics, 49, 129-135. 

Wohlrab, A., Lamer, R. and VanNieuwenhze, M.S. (2007) Total synthesis of plusbacin A3 a depsipeptide antibiotic active against vancomycin-resistant bacteria. Journal of the American Chemical Society, 129, 4175-4177. 

C28H43NO6, Mr 489.65, [a]D-49.2 (CH2CI2). A cyclic depsipeptide antibiotic from the blue alga (cyanobacterium) Hapalosiphon welwitschii. H. is able to counteract the resistance of certain tumor cells to cytostatic agents and thus (experimentally) potentiates the action of anti-cancer drugs. 

Cyclic depsipeptide antibiotics from Pacific marine sponges of the genus Theonella. On account of their macrolide structures, they are also known as Theonella peptolides. 

Bicyclic depsipeptide antibiotic. Prod, by Chromobacterium violaceum. Antitumour agent. Prisms. Mp 235-245° dec. [ag +39 (c, 1 in CHCI3). 

Depsipeptide antibiotic. Prod, by Aureobasidium pullulans. Antifungal agent. Powder. Related to Aureobasidin AI, A-03063. 

Depsipeptide antibiotic. Metab. of the fungus Beauveria sp. Shows insecticidal props. Needles (MeOH). Mp 244-246°. [ag -25 (c, 0.36 in CHClj/MeOH). 

Depsipeptide antibiotic. Isol. from an imperfect fungus, strain D1084. Nematocidal agent. Needles (dioxan aq.). Mp 188-189° dec. [a]g -201.8 (c, 0.45 in MeOH). Related to Destruxin A, D-00578. 

Cyclic depsipeptide antibiotic. Prod, by the fungus Metarhizium anisopliae. 

Depsipeptide antibiotic. Isol. from Dolabella auricularia. Cytotoxic agent. Needles (CH2Cl2/hexane). Mp 173-174°. [(xf -25.5 (c, 0.6 in MeOH). 

Cyclic depsipeptide antibiotic. Prod, by the proposed genus Sehekia sp. Active against gram-positive bacteria. Related to Antibiotic S 54832A, A-02301 and Nosiheptide, N-00824. 

Depsipeptide antibiotic. Isol. from the blue-green alga Hapalosiphon welwitschii. Shows multidrug-resistance reversing activity. Solid. [a],j -49.2 (c, 0.35 in CH2CI2). 

Depsipeptide antibiotic. Isol. from the mollusc Elysia rufescens and the alga Bryopsis sp. Cytotoxic. White powder, [a] —8 (c, 4.32 in MeOH). 

Depsipeptide antibiotic. Isol. from Microcystis aeruginosa. 

CstH N O.s M 1020.144 Bicyclic depsipeptide antibiotic. Prod, by a marine Streptoniycete. Mod. active against gram-positive bacteria. Pale yellow solid. 

Echinomycin, quinomyein A a depsipeptide antibiotic isolated from Streptomyces echinalus and effective against Gram-positive bacteria. It contains two quinoxalinoic acid residues as heterocomponents. 

Enniatins ring-shaped depsipeptide antibiotics produced by the fungus Fusarium orthoceras var. en-niatum and other Fusaria. Enniatin A, cyclo-(-D-Hyv-MeIle-)j and enniatin B, cyclo-(-D-Hyv-MeVal-)3... 

Cyclic depsipeptide antibiotics. Struct, shown is S 54832A-I. Isol. from Micro-monospora globosa. Active against gram-positive bacteria, mycoplasms and Neisseriae sp. 

Hydroxyleucine is an amino acid (Chapter 26) that is a key component in the structures of many depsipeptide medicinal agents, such as sanjoinine (below), (a) Find the part of the sanjoinine molecule that is derived structurally from (2S,3S)-3-hydroxyleucine. (b) Although many depsipeptide antibiotics occur in nature, the quantities available are too small to be useful pharmaceutically thus these molecules must be synthesized. (25,35)-3-Hydroxyleucine, which is also not available in quantity from nature, must be synthesized as well. Possible starting materials are the four diastereomers of 2-bromo-3-hydroxy-4-methylpentanoic acid (below). Draw structural formulas for each of these diastereomers and identify which of the four should be the best starting material for a preparation of (25,35)-3-hydroxyleucine. 

---