Structure of oxazolomycin,a novel β-lactone antibiotic

The structure of oxazolomycin exhibiting antitumor activity has been elucidated.     

Confirmation of the structure of a glucono-1,4-lactone derivative obtained from silylation of glucono-1,5-lactone

Silylation reactions of glucono-1,5-lactone can give the persilylated glucono-1,5-lactone or the persilylated 1,4-lactone depending on the reaction conditions employed. The structure of 2,3,5,6-tetra-O-(tert-butyldimethylsilyl)-d-glucono-1,4-lactone, obtained in 84% yield from the reaction of glucono-1,5-lactone with TBSOTf and lutidine in dichloromethane, has been confirmed by X-ray crystallography. Formation of the glucono-1,5-lactone and manno-1,5-lactone derivatives and other possible products has also been ruled out by synthesis of possible exo-glycal derivatives of these lactones using the Ramberg–Bäcklund rearrangement of the corresponding sulfones.     

Synthesis of a functionalized 7,6-bicyclic spiroimine ring fragment of the spirolides

The asymmetric synthesis of a functionalized 7,6-spiroimine related to the spirolides is described. Intermolecular Diels-Alder cycloaddition of a chiral trisubstituted dienophile and Danishefsky's diene enabled simultaneous installation of the C7 and C29 stereocenters. Further transformations and late-stage aza-Wittig cyclization afforded the spiroimine in good yield. During this study, an unprecedented 14-membered dialdimine was also obtained.     

Synthesis of heterospirans containing a γ-lactone ring

Reactions of α-ketols with diethyl malonate at the molar ratio 2:1 in the presence of K₂CO₃ were investigated. The heterospiranes obtained contained a dihydrofuran and a γ-lactone rings. The optimum conditions for the synthesis of heterospiranes were found by varying the ratio of the initial compounds: α-ketoalcohol (or 2-ethoxycarbonyl-, 2-methoxycarbonyl-, 2-cyano-3,4,4-trimethyl-2-buten-4-olides), diethyl malonate, K₂CO₃, by varying the environment, and also the temperature and the time of the reaction.     

Synthesis and Enzyme-Inhibition Studies of Phenylsemicarbazones derived from D-glucono-1,5-lactone and 2-acetamido-2-deoxy-D-glucono-1,5-lactone

The carbohydrate-derived lactone phenylsemicarbazones 3 and 4 were prepared from 5 and 8 (Scheme). Treatment with 4-phenylsemicarbazide gave 6 and 7 (77:23) and 9 and 19 (76:24), respectively. Oxidation of 6 and 9 by CrO₃–pyridine to 11 and 13 , followed by deprotection, yeilded 3 and 4 . The structure of 3 was established by X-ray analysis. Enzyme-inhibition studies using revealed that 3 is a competitive inhibitor with K_i = 23 μm. The activity of 4 was examined using N-acetylglucosaminidase from bovine kidney, Aspergillus niger, and Artemia salina. compound 4 was found to be a competitive inhibitor of all three enzymes with K_i values of 0.13, 6.0, and 0.71 μm and K_M/K_i values of 6910, 45, and 465, respectively.     

The first synthesis of N-acetylneuraminic acid 1,7-lactone

N-Acetylneuraminic acid is transformed into its until now unavailable and rather unwieldy 1,7-lactone, via the manageable 2-benzyloxycarbonyl N-acetylneuraminic acid 1,7-lactone which generates the free lactone in quantitative yield by hydrogenolysis.     

Novel synthesis of L-ribose from D-mannono-1,4-lactone

[reaction: see text] D-Mannono-1,4-lactone was efficiently converted into L-ribose in eight steps. A key step of this synthesis is the cyclization of a gamma-hydroxyalkoxamate under Mitsunobu conditions. It is noteworthy that the O-alkylation product was obtained in 94% yield and that none of the N-alkylation product was detected in this cyclization.     

First synthesis of 4,5-O-isopropylidene-6-thio-d-galactono-1,6-lactone as a precursor of d-galactothioseptanose

Displacement of the bromide group in methyl 6-bromo-6-deoxy-2,3:4,5-di-O-isopropylidene-d-galactonate 7, with potassium thioacetate gave methyl 6-(S)-acetyl-2,3:4,5-di-O-isopropylidene-6-thio-d-galactonate 8 in quantitative yield. Regioselective removal of the 2,3-ketal protecting group afforded methyl 6-(S)-acetyl-4,5-O-isopropylidene-6-thio-d-galactonate 11 in 70% yield. Saponification of compound 11 gave the 6-(S)-4,5-O-isopropylidene-6-thio-d-galactonic acid 12 in quantitative yield. Treatment of 12 with DIC/HOBt as coupling reagents gave, after cyclisation; the target compound: 4,5-O-isopropylidene 6-thio-d-galactono-1,6-lactone 13 in 49% yield.     

Reactions affecting the γ-lactone ring of α-santonin

The selective dehydrogenation of the eudesmanolide α-santonin and its alkylation with the introduction of an allyl fragment into its γ-lactone ring are described. It has been established that these reactions are regio- and stereo-selective. The structures of the compounds obtained were determined from their IR, UV, PMR, and mass spectra. Institute of Organic Synthesis and Coal Chemistry, Kazakhstan Academy of Sciences, Karaganda. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 518–522, September–October, 1992.