Synthese von Desacetoxycephalosporin‐S‐oxiden aus Penicillin‐S‐oxiden durch oxidativen Einfang der intermediär entstandenen Sulfensäure‐Gruppierung

Abstract

Das cyclische Acylphosphat (5) N-methyliert Pyridin zu ( l o ) , aus dem ( 5 ) mit Trimethyloxonium-tetrafluoroborat zuriickerhalten wird. DaB der nucleophile Angriff des Pyridins am Methyl-Kohlenstoffatom von (5) -und nicht am elektrophilen Phosphoratomstattfindet, ist laut Abschatzung der Aktivierungsenergie in Anlehnung an die Methode von Szabo['] darauf zuriickzufuhren, daD gleichzeitiges Losen einer C-0-Bindung und Entstehen einer C-N-Bindung energetisch giinstiger ist als die Kniipfung einer P-N-Bindung unter Spaltung einer P-0-Bindung.Die Hydrolyse von ( l o ) erfolgt bei 25°C rasch unter Decarboxylierung zu (11), R =H, wahrend die Alkoholyse bzw. Phenolyse ( I I ) , R=Alkyl bzw. Aryl, ergibt, wobei primare Alkohole erheblich rascher als sekundare verestert werden.

Preparation and isomerization of 5-epibenzylpenicillins

“…In particular, the formation of compounds 6 and 7 upon treatment of 3 with DBN requires the inversion of the configuration of C-3, which, in principle, may be in- duced by removal of the 3-H atom (V). However, epimerization at position 6 (la) which may result in the formation of the 5-epi-6 epimer (5), cannot be excluded on the basis of our results, since the absence of compound 5 in the reaction mixture can be explained either by the fact that it is unstable under the reaction conditions used, or that it is not formed as a result of a still larger free-energy difference between 3 and 5 than between 4 and 1. Since in 5-epipenicillins 3-H has the exo stereochemistry, whereas 6-H as well as the 3 substituent are both at the endo side of the molecule, removal of the 3 hydrogen may become competitive if not preferred to the deprotonation at C-6, although this latter hydrogen is intrinsically more acidic.…”

“…Solutions of lax10 (0.696 g, 2 mmol) in anhydrous methylene chloride (5 ml) were treated with BSA (1.2 ml, 5 mmol) for 2 h at room temperature. The silylated penicillanate was then isomerized with DBN (1 equiv) for 15 min and for 5 h, or with triethylamine (5 equiv) for 24 and 48 h. The reaction mixtures were worked up as described for the 5 epimer, and were analyzed by NMR after purification by column chromatography on silica gel using benzene-acetone (98:2) as eluent.…”

“…Treatment of lax with an equivalent amount of chlorine yielded a mixture of 25% of 2axv and 75% of 2axw (as determined by NMR). Attempts to cyclize this mixture with SnCl2 gave several compounds of unknown structure but no 5 epimer could be detected. It should be noted that chlorinolysis of the S1-C5 bond in benzylpenicillin in the presence of an excess of chlorine has led to an olefinic azetidinone, which has been cyclized to a thiazabicycloheptenone.…”

“…It should be noted that chlorinolysis of the S1-C5 bond in benzylpenicillin in the presence of an excess of chlorine has led to an olefinic azetidinone, which has been cyclized to a thiazabicycloheptenone. 5 This negative result prompted an attempt to remove the phthaloyl group with hydrazine in dimethylformamide, a method which has been used successfully in the cephalosporin series. 6 Application of this procedure to 3bx gave methyl 6-amino-5-epipenicillanate (3cx) in 75% yield.…”

Azetidinone antibiotics. 19. A simple method for the removal of p-nitrobenzyl acid-protective group

“…Yield of pure product; 500 mg (46%); NMR (CDC13 + DMSO-d6) 6.19 (s, 2 H, C2-H2), 5.45 (s, 2 H, «-CH2), 4.97-4.87 (d and s, 3 H, C4-H and C6-H), 4.60 and 4.30 (2s, 2 H, C3-CH2), 4.09 (q, 1 H, C7-H), 3.14-2.52 (m, 5 H, aromatic H), and O. 21 (d. 1 H, amide-NH); IR (Nujol mull) 1668,1735 and 1758 cm-1.…”