5-Hydroxy[1,2]oxazinan-3-ones as potential carbapenem and D-ala-D-ala surrogates

Abstract

The title compounds are amino acids whose nitrogen atom is enclosed in a six-membered cyclic hydroxamate bearing a C5-hydroxyl group. They belong to a proposed new family of antibacterial agents targeted to the penicillin receptor. The glycine and alanine members of the family have been synthesized, as racemates, in seven steps from the four-carbon synthon diketene and the tert-butyl esters of N-hydroxyglycine and N-hydroxyalanine. Numerous alternatives to diketene have also been examined, but these lead mainly to five-membered cyclic hydroxamates. The theoretical considerations that have led to this synthetic programme are discussed in some detail. They include analysis of the structures of natural and unnatural penicillin surrogates, analysis of the penicillin pharmacophore, and a treatment of the chemical reaction with which penicillin blocks bacterial cell wall synthesis. The glycine derivative exhibits marginal but real activity vs. Micrococcus luteus. The alanine derivative, which more closely resembles D-ala-D-ala, is fifty times more active. Two five-membered structural isomers of the glycine derivative are inactive. Key words: cyclocanaline, cycloserine, lactivicin, oxamazins, peptidoglycan, penicillin-binding proteins.

Amidine−Oximes: Reactivators for Organophosphate Exposure

“…In path B, benzyl-protected ethyl glyoxylate oxime 10 was synthesized as described before . Ester 10 was treated with ammonia or alkyl amine MeNH 2 , EtNH 2 , PrNH 2 to afford 11a − d (Scheme ).…”

“…In path B, benzyl-protected ethyl glyoxylate oxime 10 was synthesized as described before. 25 Ester 10 was treated with ammonia or alkyl amine MeNH 2 , EtNH 2 , PrNH 2 to afford 11aÀd (Scheme 2). Thioamides 12aÀd were obtained by treating 11aÀd with Lawesson's reagent in good yield.…”

Stabilizing Factors for Vanadium(IV) in Amavadin

“…The CHN elemental analyses were performed at the Dr. Verwey Chemical Laboratory in Rotterdam, The Netherlands. The α‐bromo acids,50,51 α‐hydroxy acid esters,52,53 N ‐hydroxyglycine ethyl ester54 and ( R )‐ N ‐phenylalanine methyl ester ( 11 )46 were prepared according to literature procedures. We have previously reported the synthesis of 13b and the NMR spectroscopic data of its PPh 4 salt after oxidation to V V 42.…”

“…Synthesis of Nitrones 7: The nitrones 7a , 7b and 7g were synthesized and isolated according to literature procedures 43,54…”

Evaluation of Substituted 1,2,3‐Dithiazoles as Inhibitors of the Feline Immunodeficiency Virus (FIV) Nucleocapsid Protein via a Proposed Zinc Ejection Mechanism

“…Ethyl (5 Z )‐5‐(phenylimino)‐5 H ‐1,2,3‐dithiazole‐4‐carboxylate (12 d) : Ethyl ( E )‐2‐(hydroxyimino)propanoate 9 g (131 mg, 1 mmol) was treated according to general procedure C to afford compound 12 d as a red oil (154 mg, 58 %): Anal. calcd for C 11 H 10 N 2 O 2 S 2 (%): C 49.61, H 3.78, N 10.52, found (%): C 49.88, H 4.02, N 10.42; 1 H NMR (300 MHz, CDCl 3 ): δ =1.43 (3 H, t, J =7.3 Hz, CH 3 ), 4.38 (2 H, q, J =7.3 Hz, CH 2 ), 7.16 (3 H, m, Ph), 7,46 ppm (2 H, m, Ph); 13 C NMR (75.5 MHz, CDCl 3 ): δ =14.2 (CH 3 ), 63.0 (CH 2 ), 119.3 (2 CH, Ph), 126.4 (CH), 129.8 (2 CH, Ph), 139.4, 152.1, 153.3, 160.4 ppm (4 sp 2 tertiary C); MS (EI, 70 eV), m / z (%): 266 (40) [ M ] + , 167 (80); IR (KBr): =3076, 2960 (C−H), 2924, 2852, 1744 (C=O), 1700 (C=O), 1584, 1540, 1484, 1368, 1216, 1144, 740, 676 cm −1 …”