Giuseppe Cassinelli

Mass spectrometry of some N-acyldaunosamine derivatives.

Abstract The principal modes of fragmentation subsequent to electron impact of some N -acyl derivatives of daunosamine, the glycoside moiety of the antitumour antibiotics daunomycin and adriamycin, have been studied by using specifically deuterated derivatives and high-resolution measurements. In particular, the elimination of MeOH from methyl β-daunosaminides is shown to occur extensively and stereo-specifically, and involves HO-4. The splitting of the moieties C-1-C-2 and C-5-O-5 affords the fragments D 2 , D ′ 2 , and D ′′ 2 , which are among the most abundant.

New antibiotics produced by streptoverticillium orinoci, n. sp.

SummaryThree new antibiotics, neoantimycin, neaureothin and ochramycin have been isolated from Streptoverticillium orinoci. The systematic position of the organism is discussed.Neoantimycin is related to the antimycin antibiotics group; neoaureothin shows some similarity with aureothin. Ochramycin is an amphoteric compound containing in its molecule an octaene chromophore.The first two antibiotics show a slight antifungal activity only. Ochramycin is active against gram +ve, but not against gram -ve bacteria; its activity against yeasts and fungi is very slight.Toxicity data are reported; no therapeutical effectiveness has been observed in experimental infections in mice.

Synthesis of novel cephem-4-ketones. A new series of human leukocyte elastase inhibitors

Alkylation of cephem-4-carbonyl chlorides at the sulphide or sulphone oxidation level with Grignard reagents, stannanes and cuprates is described. Radical or ionic bromination of the 3-methylcephem-4-ketone 8, followed by displacement with heterocyclic thiols, provides an entry to 3′- and 2-thiosubstituted derivatives, which are new potent inhibitors of HLE. Alkylation of cephem-4-carbonyl chlorides with Grignard reagents, stannanes or cuprates, prior or after oxidation, gave 3a≈f(X Cl; R But, Et, Ph.Bz.H; R′OAc). Similarly, 8 (X OMe, R But, R′ H) was prepared and converted to 13a≈c (R′ S-Het) and 14a≈c via radical and ionic bromination, respectively. The new cephem-4-ketones are potent inhibitors of human leukocyte elastase.

Synthesis of new branched-chain aminodeoxyhexoses related to daunosamine (3-amino-2,3,6-trideoxy-l-lyxo-hexose)

Abstract Addition of methylmagnesium iodide to methyl 2,3,6-trideoxy-3-trifluoro-acetamido-α- l - threo -hexopyranosid-4-ulose (3) gave methyl 2,3,6-trideoxy-4- C -methyl-3-trifluoroacetamido-α- l - lyxo -hexopyranoside (4) and its l - arabino analogue, depending upon the reaction temperature and the solvent. The corresponding 4- O -methyl derivatives were obtained by treatment of 4 and 5 with diazomethane in the presence of boron trifluoride etherate. Treatment of 4 with thionyl chloride, followed by an alkaline work-up, gave methyl, 2,3,4,6-tetradeoxy-4- C -methylene-3-trifluoro-acetamido-α- l - threo -hexopyranoside (8) , which was stereoselectively reduced to methyl 2,3,4,6-tetradeoxy-4- C -methyl-3-trifluoroacetamido-α- l - arabino -hexopyranoside. Epoxidation of 8 with 3-chloroperoxybenzoic acid gave the corresponding 4,4 1 -anhydro-4- C -hydroxymethyl- l - lyxo derivative (10) , which was also prepared by treatment of 3 with diazomethane. Azidolysis of 10 , followed by catalytic hydrogenation and N -trifluoroacetylation, gave methyl 2,3,6-trideoxy-3-trifuloroacetamido-4- C -trifluoroacetamidomethyl-α- l - lyxo -hexopyranoside.

Synthesis of derivatives of 3-amino-2,3-dideoxy-l-hexoses related to daunosamine (3-amino-2,3,6-trideoxy-l-lyxo-hexose)

The synthesis is described of 3-amino-2,3-dideoxy-L-arabino-hexose (10), methyl 2,3-dideoxy-alpha-L-lyxo-hexopyranoside(17), methyl 3-amino-2,3-dideoxy-alpha-L-ribo-hexopyranoside (21), methyl 2,3-dideoxy-3-trifluoroacetamido-alpha-L-xylo-hexopyranoside (26), and certain derivatives from methyl 4,6-O-benzylidene-2-deoxy-alpha-L-arabino-hexopyranoside (3). Conversion of 2-deoxy-L-arabino-hexose into 3 by modified, standard procedures, and on a large scale, gave a 75% yield.