Wataru Nagata

Synthetic studies on β-lactam antibiotics. VII. Mild removal of the benzyl ester protecting group with aluminum trichloride☆

The benzyl ester protecting group in β-lactam derivatives can be cleanly removed by treatment with aluminum trichloride under mild conditions, preferably in the presence of anisole, to give the corresponding free acids in high yields.

Stereocontrolled, straightforward synthesis of 3-substituted methyl 7α-methoxy-1-oxacephems☆

Abstract Stereocontrolled and industrially feasible synthesis of a new antibiotic 1a and related derivatives, which is characterized by using all the carbon atoms of the penicillin skeleton, is described.

Reduction and Reductive Alkylation of α-tert-Butylthio Carbonyl Compounds. An Efficient Method for Stepwise α-Alkylation of Esters, Nitriles and Ketones Via the α-Tert-Butylthio Derivatives

Abstract An efficient and generally applicable method for stepwise α-alkylatton of esters, nitriles, and ketones via the α-tert-butylthio derivatives is described. The method involves reductive-protonation and reductive-alkylation of α-alkylthio α,α-bis-alkylated carbonyl compounds which are prepared by stepwise alkylation of the corresponding simple α-alkylthio carbonyl precursors. The reduction is conveniently performed by use of stoichiometric amounts of a dissolving metal, particularly lithium, affording correspondingly the α-mono-and the α,α-bis-alkylated carbonyl compounds in good yields.

An alternative synthesis of the 1-oxacephem skeleton

Abstract 1-Oxacephem skeletons were constructed in a convergent manner starting from building blocks B and C , which were easily prepared from penicillin and diketene, respectively, followed by intramolecular carbene insertion reaction of the resulting intermediate A .

Synthetic studies on β-lactam antibiotics. Part 16. synthesis of 1-carba-2-penem-3-carboxylic acid esters from penicillins utilizing a carbon-carbon coupling reaction

Abstract Allylazetidinones 9 , 10 , prepared by coupling of allylcoppers 8 with chloroazetidinones 6 , 7 , were converted into carbapenem esters 16 , 28 – 31 using an Emmons-Horner reaction to introduce the 6-side chain and an intramolecular Wittig reaction to form the carbapenem ring system.

New route to 3-(substituted) methyl 1-oxa- and (1-thia)cephems from 3-exomethylene intermediates via sulfenyl chloride adducts

Abstract Addition of methane- and benzenesulfenyl chlorides to 3-exomethylene-1-oxacephams 10 and 14 gave 3β-sulfenyl-3α-chloromethyl adducts 11 and 15. Nucleophilic substitution of the adducts proceeded facilely to afford compounds 18–23, which were converted into Δ3-derivatives 26 and 27 by oxidative elimination. This new route, as illustrated by the sequence 6→7→8→3, has an essential advantage in using the saturated intermediates 7 and 8 with a stabler β-lactam ring which is compatible in nucleophilic substitution, alkaline ester hydrolysis and further manipulations. These synthetic features are well demonstrated by successful synthesis of 1-oxacefamandol 35 and 7β-(2-thienylacetyl-amino)-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3- acid (45)

1-Oxacephems with the Thienamycin-Type Side Chain(1). Synthesis and Antibacterial Activity of 7a-[(1R)-1-Hydroxyethl]1-1oxacephems Bearing Electron-Withdrawing Groups

1-Oxacephem derivatives, 2a-d, bearing the hydroxyethyl group at C 7α and some electron-withdrawing groups at C 3 were synthesized and tested for antibacterial activity. It was found that some of these compounds, in particular, 7α-hydroxyethyl-3-cyano-1-oxacephem 2d, exhibited antibacterial activity, although the potency was low. Some 7α-hydroxyethyl-2-oxo-1-oxacephems, 1a,b, were also prepared and found biologically inactive

Bridged Azibidines. iii. Lead Tetra-Acetae Oxidation of 5-Aminocycloheptene. Synthesis of Dl-2α-Hydroxytrop Ane

Abstract 5-Aminocycloneptene 3 was oxidized with lead tetraacetate in benzane in the presence of anhydrous potasium carbonate at room tamperature giving the bridged aziridine 4 in ca. 90% yield, this providingand additional example of the new nitrenoid reactionwhich was recently discovered in our laboratory. The aziridine 4 was transformed smoothly intothe 2a-substituted tropanes 13 and 17 and a new synthetic route to these important azacycles was thus established.

Practical procedure for epimerization of 7α-amino-1-oxacephems to 7β-amino epimers

Abstract 7α-Amino-1-oxacephems can be epimerized to their 7β-amino epimers by treatment with chloral to give Schiff bases, followed by dehydrochlorination with Hunig base, borohydride reduction, and hydrolysis.

One-step synthesis of oxazolinoazetidinones from penicillin sulfoxides: potential intermediates for 1-oxacephem synthesis

Abstract Reaction of penicillin sulfoxides with a tervalent phosphorous compound in the presence of a catalytic amount of squaric acid gave oxazolinoazetidinones, potential intermediates for synthesis of 1-oxacephems, in good yields.2β-Chloromethyl- and 6α-methoxypenicillin sulfoxides also undergo this reaction. The reaction contrasts with the well-known Cooper reaction which usually gives thiazolinoazetidinones.