Glycosylidene Carbenes. Part 32

Abstract

Dedicated to the memory of Jorge F. Lo¬pez-Herrera Acylation and sulfonylation of the N,N'-unsubstituted glucosylidenespirodiaziridines 1A/1B 95 : 5 with Ac 2 O, BzCl, FmocCl, TsCl, (naphthalen-2-yl)sulfonyl, and (2,4,6-triisopropylphenyl)sulfonyl chloride, and concomitant rearrangement gave the acylated and sulfonylated gluconolactone hydrazones 2B ± 2G in 40 ± 83% yield (Scheme 2). Similarly, the galacto and manno analogues 3A/3B 95 : 5 and 5A/5B 55 : 45 and the mannofuransoylidene-diaziridine 30 were acetylated and tosylated to give 4A, 4B, 6, 31A, and 31B (55 ± 73% yield; Schemes 2 and 5). 15 N-Labelling of 11A/11B and 14A/14B showed that the pseudoequatorial NH of the gluco diaziridines 1 and the pseudoaxial NH of the galacto diaziridines 3 were preferentially acetylated and tosylated (Scheme 3). Sulfonylation of the N-methylated diaziridines 19A/19B 72 : 28, 22A/22B 85 : 15, 25A/25B 85 : 15, 28A/28B 80 : 20, and 33A/33B/33C/33D 76 : 4 : 12 : 8 yielded the N-methyl-N-tosylglyconolactone hydrazones 20, 23, 26, 29, and 34 (44 ± 66%; Schemes 4 and 5). The methylated N-atom of the diaziridines proved more reactive, irrespective of the configuration at C(2) and C(4). The products were readily hydrolysed to glyconolactones.Introduction. ± The reactivity of glycosylidene diaziridines has not been wellexplored. Apart from an investigation of their formation [1], with special emphasis on the stereoselectivity of the addition of NH 3 and MeNH 2 to the precursor glyconolactone oxime sulfonates [2], only the oxidation of these diaziridines with iodine and Et 3 N or Me 3 N in MeOH, Et 2 O, or CH 2 Cl 2 [3] to N-unsubstituted-glycosylidene diazirines was investigated. These diazirines have been studied as precursors of glycosylidene carbenes [3 ± 5].The reactivity of 3-alkyldiaziridines has been explored more extensively. Their reaction with electrophiles is strongly influenced by the nature of the electrophile and by the N-substituents. Attack of electrophiles on the diaziridines I leads to diaziridinium ions II (Scheme 1). For R 3 H, deprotonation of II afforded substituted diaziridines III [6 ± 10]. Alternatively, diaziridine ring opening of II led to the hydrazonium ions IV, which were transformed into hydrazones V (R 4 H) [11] [12] and into azomethine imines VI (R 3 H) [13]. Hydrolysis of IV afforded ketones VII and hydrazines VIII [13a] [14] [15]. This transformation to hydrazines constitutes a valuable method for the selective preparation of otherwise hardly accessible N -alkyland N,N'-dialkylhydrazines [16]. The reaction of 1,3,3-trimethyldiaziridine with AcCl led to a 4 : 1 mixture of N-methyl-N'-isopropylidene-acethydrazide and 2-acetyl-1,3,3trimethyldiaziridine [17].Except for the oxidation with I 2 , we found no reaction of glycosylidene diaziridines, nor of any other 3-alkoxydiaziridine with electrophiles. We have examined the reactions of glycosylidene-diaziridines with acylating and sulfonylating reagents, and describe the results of these experiments.Results and Discussion. ± 1. Acylation and Sulfonylation...

2-Acetamido-2-deoxy-d-glucono-1,5-lactone Sulfonylhydrazones: Synthesis and Evaluation as Inhibitors of Human OGA and HexB Enzymes

“…Although some glycono-1,5-lactone tosylhydrazones are known in the literature [13][14][15], no analogous derivatives of 2-acetamido-2-deoxy-D-glucono-1,5-lactone could be found. Therefore, the synthesis of the planned inhibitors (Table 2) was based on our previous work [12] encompassing the synthesis of 2-acetamido-2-deoxy-D-glucono-1,5-lactone semicarbazones.…”

Catalytic Orthogonal Glycosylation Enabled by Enynal‐Derived Copper Carbenes

“…Because of the instability of diazirines, they then employed the anomeric N ‐tosylhydrazone donors, which are benchtop stable carbene precursors. The sodium salts of these N ‐tosylhydrazones under photochemical conditions generate the corresponding anomeric carbenes, which undergo an O−H insertion reaction with alcohols to form O ‐glycosides (Scheme 1a) [13c] . A similar anomeric carbene has also been employed in protecting group‐free phosphorylations [14] .…”

Synthesis and fungicidal activity of novel 1,3‐disubstituted 1H‐diazirine derivatives

“…From the 60s, various substituted diaziridines and diazirines were synthesized [29–43]. Halogen derivatives are ideal precursors for spectroscopic studies of carbens [44–46]; several derivatives were suggested as alkylating agents [47] and potential reagents for photolabeling of biological receptor sites [48–57], some of the substituted diaziridines and diazirines were investigated as anticancer drugs [58, 59], potential monoamine oxidase inhibitors [60, 61] and anesthetics [62, 63].…”