Studies on new dehydropeptidase inhibitors. IV. Chemical transformation of WS1358 compounds and an improved synthesis of WS1358A1

The structures of compounds 3 (and 4) and 5 (and 6) derived from the natural products WS1358A1 (1) (and B1 (2)) have been determined by their spectroscopic evidence. By taking advantage of these transformations, an improved synthesis of A1 (1, racemate) has been achieved.     

Studies on new dehydropeptidase inhibitors. III. Biological properties of WS1358A1

WS1358A1, a novel inhibitor of renal dehydropeptidase (DHP), augmented the urinary recovery of a carbapenem antibiotic imipenem and improved its protective effect in experimental infections when simultaneously administered to mice with the antibiotic. WS1358A1 was a competitive DHP inhibitor with a Ki value of 1.6 x 10(-7) M.     

Propioxatins A and B, new enkephalinase B inhibitors. II. Structural elucidation

The structures of propioxatins A (C17H29N3O6) and B (C18H31N3O6), new enkephalinase B inhibitors produced by Kitasatosporia setae SANK 60684, were determined. Both propioxatins consist of N-acyl-L-prolyl-L-valine. N-Acyl moieties of propioxatins A and B were alpha-propyl and alpha-isobutyl succinic acid beta-hydroxamic acid, respectively.     

Studies on new antifungal antibiotics, guanidylfungins A and B. II. Structure elucidation and biosynthesis

The structures of guanidylfungins A and B were elucidated from the physico-chemical properties of these compounds and the structures of the degradation products by ozonolysis and periodate oxidation. The guanidylfungins consist of a 36-membered polyhydroxyl lactone ring, a guanidine and a monoester of malonic acid. The labelling experiments with sodium [1-13C]acetate and sodium [1-13C]propionate revealed that twelve units of acetate and nine of propionate were incorporated into the molecule of guanidylfungin A.     

Studies on new dehydropeptidase inhibitors. I. Taxonomy, fermentation, isolation and physico-chemical properties

WS1358A1 (FR104007) and B1 (FR104008), new potent inhibitors of renal dehydropeptidase, were isolated from the culture broth of strain No. 1358 which was identified as Streptomyces parvulus subsp. In vitro inhibitory activities (IC50 value) of WS1358A1 and B1 against porcine renal DHP were 3 and 600 nM, respectively.     

Studies on WB-3559 A, B, C and D, new potent fibrinolytic agents. II. Structure elucidation and synthesis

The structures of WB-3559 A, B, C and D, new fibrinolytic agents isolated from Flavobacterium sp. No. 3559, have been elucidated to be as shown in 1, 2, 3 and 4, respectively, on the basis of chemical and spectroscopic evidence. Total synthesis of WB-3559 D (4) was achieved starting from the optically active aldehyde 14.     

Melanocins A, B and C, new melanin synthesis inhibitors produced by Eupenicillium shearii. II. Physico-chemical properties and structure elucidation

New melanin synthesis inhibitors, melanocins A, B and C, were isolated from the fermentation broth and extract of mycelium of Eupenicillium shearii F80695. The structures of melanocins were established by spectroscopic methods. They are formamide compounds. In particular, melanocin A has an isocyanide group.     

Helvecardins A and B, novel glycopeptide antibiotics. II. Structural elucidation

Helvecardins A and B, which are produced by Pseudonocardia compacta subsp. helvetica, are new members of glycopeptide antibiotics. They contain the same pseudoaglycone as beta-avoparcin and the same compositions of neutral sugar, amino sugar, and amino acid except that 2'-O-methylrhamnose was detected in helvecardins instead of rhamnose in beta-avoparcin, and mannose was not detected in helvecardin B. From these results and 1H NMR and mass spectral analyses, helvecardins A and B were determined beta-avoparcin 2'-O-methylated on rhamnose and demanosylhelvecardin A, respectively.     

Biphenomycins A and B, novel peptide antibiotics. II. Structural elucidation of biphenomycins A and B

The structures of biphenomycins A and B, novel peptide antibiotics produced by a strain of Streptomyces, have been established as 1 and 2, respectively, on the basis of spectroscopic and chemical evidence. They are unique in that they are cyclic peptides containing a biphenyl moiety included in a 15-membered ring and show potent antibacterial activities especially against Gram-positive bacteria.     

WS-9659 A and B, novel testosterone 5 alpha-reductase inhibitors isolated from a Streptomyces. II. Structural elucidation of WS-9659 A and B

On the basis of spectroscopic and chemical evidence, the structures of WS-9659 A and B isolated as inhibitors of testosterone 5 alpha-reductase from a Streptomyces have been established as 1 and 2, respectively. The reductase inhibitory activities of the derivatives 5 and 6, and degradation products 3 and 8 were considerably less active and substantially inactive, respectively.     

Studies on new antibiotics SF2415. II. The structural elucidation

Structures of new antibiotics SF2415A1, A2, A3, B1, B2 and B3 were deduced from spectroscopic analyses and degradation studies. The structure of SF2415A3, which has the most antibacterial activity, was proposed to be 3,4a-dichloro-9-diazo-3,4, 4a,10a-tetrahydro-6-hydroxy-2,2,7-trimethyl-10a-[(E)-3,7-dimethyl- 2,6-octadienyl]-(2H,9H)naphtho-[2,3-b]pyran-5,8,10-trione. All of antibiotics SF2415 have a semi-naphthoquinone structure.     

Arugomycin, a new anthracycline antibiotic. II. Structural elucidation

The structure of arugomycin was determined by chemical degradation, and NMR and mass spectral analyses to be a new anthracycline antibiotic with arugorol (4'-epi-nogalarol) as the chromophore and two sugar chains comprising diginosyl-decilonitrosyl-2-deoxyfucose, and (4-O-fumaryl-diginosyl)-diginosyl-2-deoxyfucosyl -diginose.     

A new antitumor antibiotic, FR900840. II. Structural elucidation of FR900840

The structure of FR900840, a new antitumor antibiotic produced by a strain of Streptomyces has been deduced as 1 on the basis of spectroscopic and chemical evidence and finally confirmed by synthesis from L-threonine and L-serine.     

Studies on a new antibiotic SF-2330. II. The structural elucidation

The structure of antibiotic SF-2330 has been elucidated to be 11-hydroxy-5-methyl-2-(2,2'-bioxiran-2-yl)-4H-anthra[1,2-b] pyran-4,7,12-trione by spectral analyses. The olefinic side chain at C-2 of alpha-indomycinone is replaced by a bioxiran-2-yl group in SF-2330.     

Glidobactins A, B and C, new antitumor antibiotics. II. Structure elucidation

The structures of new antitumor antibiotics, glidobactins A (Ia), B (Ib) and C (Ic) were elucidated by a combination of chemical and enzymatic degradations and spectral analyses. They have in common a cyclized tripeptide nucleus composed of L-threonine, 4(S)-amino-2(E)-pentenoic acid and erythro-4-hydroxy-L-lysine, and differ from each other in the unsaturated fatty acid moiety attached to the peptide.     

Adxanthromycins A and B, new inhibitors of ICAM-1/LFA-1 mediated cell adhesion molecule from Streptomyces sp. NA-148. II. Physico-chemical properties and structure elucidation

Adxanthromycins A and B are new inhibitors of ICAM-1/LFA-1 mediated cell adhesion molecule isolated from the fermentation broth of Streptomyces sp. NA-148. The molecular formula of adxanthromycins A and B were determined as C42H40O17 and C48H50O22, respectively by FAB-MS and NMR spectral analyses, and the structures of both compounds were elucidated to be a dimeric anthrone peroxide skeleton containing alpha-D-galactose by various NMR spectral analyses and chemical degradation.