Cyclic hydroxamates, especially multiply substituted [1,2]oxazinan-3-ones

Abstract

Routes to putative N-acyl-D-ala-D-ala surrogates, beginning with the conversion of 4-, 5-, and 6-membered lactones into 5-, 6-, and 7-membered cyclic hydroxamates, are reported. The key step of the synthesis is trimethylaluminium-promoted cyclization of an ω-aminooxyester. The 7-membered cyclic hydroxamate crystallizes in a chair conformation. Extension of the reaction sequence to homoserine or homoserine lactone leads to cyclocanaline and N-acylated cyclocanalines. The 4-phenylacetamido derivative of cyclocanaline crystallizes in a boat conformation. The attachment of a 2-carboxypropyl substituent to the ring nitrogen of a 4-acylaminocyclocanaline has been effected, prior to cyclization, by coupling of the acyclic aminooxyester precursor to the triflate of benzyl lactate or, after cyclization, by coupling to tert-butyl α-bromopropionate in the presence of potassium fluoride – alumina, followed by removal of the protecting group in each case. A six-membered homolog of the antibiotic lactivicin has been synthesized by the reaction of 4-phenylacetamidocyclocanaline with benzyl 2-oxoglutarate in the presence of carbodiimide, followed by hydrogenolysis. Starting with methyl 2,4-dibromo-2,4-dideoxy-L-erythronate, which is available in two steps from L-ascorbic acid, these reaction sequences have been applied to the stereospecific synthesis of a D-alanine derivative whose nitrogen atom is enclosed within a 3,4-disubstituted [1,2]oxazinan-3-one. Key words: D-ala-D-ala surrogate, cyclocanaline, homolactivicin, peptidoglycan, trimethylaluminium.

Synthesis of γ-hydroxy-α-(arylmethyl)carboxylic acids from lactones: pathway to a structural motif derived from lactic acid and amino acid analogs?

“…Recent examples describe the recovery of the lactone by extraction after protonation of the γ-hydroxycarboxylate [17]. On the other hand, the isolation of the free γ-hydroxycarboxylic acid after acidification of the potassium salt and subsequent extraction is reported, too [18]. Commonly, the γ-hydroxycarboxylate is protonated in situ [19] or the crude mixture after acidification of the γ-hydroxycarboxylate is directly used for further transformations [20, 21].…”

Author reply

“…Benzyl lactates were prepared following Wolfe et al27 The product was distilled under vacuum (85 °C at 0.15 mmHg) to give a clear liquid (65.6 g, 78%).…”

Synthesis of Hydroxylamines

“…Intermolecular reactions of hydroxylamines with secondary alkyl halides and mesylates proceed slower than with alkyl triflates and may not provide sufficiently good yield and/or stereoselectivity 38 . A useful alternative for these reactions is application of more reactive anions of O-alkylhydroxamic acids 39 or O-alkoxysulfonamides 40 like 12 (equation 8) as nucleophiles.…”