Simple and condensed β-lactams-I

Simig, Gyula; Doleschall, Gábor; Hornyák, Gyula; Fetter, J.; Lempert, K.; Nyitrai, J.; Huszthy, Péter; Gizur, T.; Kajtár-Peredy, Mária

doi:10.1016/s0040-4020(01)96442-7

Cited by 18 publications

(18 citation statements)

References 6 publications

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“…microwave conditions), the reaction time., no substitution of either the mesyloxy or the tosyloxy group by cyanide could be achieved. Therefore, inspired by similar cases concerning 4-(mesyloxymethyl)azetidin-2-ones described in the literature, [49][50][51] an alternative approach was studied consisting of the Scheme 1 preliminary conversion toward more reactive 4-iodomethyl-blactams 10a-c as versatile intermediates, 52-54 as iodide is considered to be a very good leaving group combined with the expected decrease in steric hindrance during the substitution reactions as compared to sulfonyloxy leaving groups. 51 Both 4-mesyloxymethyl-and 4-tosyloxymethyl-b-lactams 8a,b and 9a-c were therefore converted into the corresponding iodides 10a-c by means of an excess of sodium iodide in acetone under reux (69-97%).…”

Section: Resultsmentioning

confidence: 99%

“…of sodium cyanide in DMF. 51 It must be mentioned that the KCN-mediated direct displacement of 3-non-substituted 4-(tosyloxymethyl) azetidin-2-ones has been performed only once before, using 18-crown-6 as an additive, whereas sulfonyloxy displacements by cyanide in 3-substituted b-lactams have not been reported so far. 55 In the next stage, the selective hydrolysis of the nitrile function within the synthesized (3R,4S)-3-alkoxy/aryloxy-4-cyanomethyl-b-lactams 11a-c was studied.…”

Section: Resultsmentioning

confidence: 99%

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A nitrilase-mediated entry to 4-carboxymethyl-β-lactams from chemically prepared 4-(cyanomethyl)azetidin-2-ones

et al. 2016

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3R,4S)-3-Alkoxy/aryloxy-4-(cyanomethyl)azetidin-2-ones were efficiently prepared from readily available 1,2:5,6-di-O-isopropylidene-D-mannitol by means of a classical organic synthesis approach via 4-hydroxymethyl-b-lactams as key intermediates. The corresponding 4-carboxymethyl-b-lactams were subsequently obtained after selective hydrolysis of the nitrile functionality by means of a nitrilase enzyme without affecting the sensitive four-membered ring system, hence overcoming the difficulties associated with the chemical hydrolysis approach. Thus, the implementation of a biocatalytic step allows a convenient synthetic route to new 4-carboxymethyl-b-lactams as versatile building blocks for further elaboration.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

A nitrilase-mediated entry to 4-carboxymethyl-β-lactams from chemically prepared 4-(cyanomethyl)azetidin-2-ones

et al. 2016

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“…Simig and co-workers have described the formation of the chloride 19 directly from the alcohol 17 in 53 % yield [7]. Their reaction conditions were harsh compared with ours and involved treating the alcohol 17 with methanesulfonyl chloride in boiling pyridine solution.…”

Section: Sep-oct 2005mentioning

confidence: 87%

Possible neighbouring group participation of a nitro-group in the conversion of 3-hydroxymethyl-2-(2-nitrophenyl)-1,2,3,4-tetrahydroisoquinoline into its 3-chloromethyl derivative

Donaghy

Stanforth

2005

Journal of Heterocyclic Chemistry

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The alcohol 12 reacted with 4-toluenesulfonyl chloride in boiling dichloromethane solution to give the chlorinated product 13 rather than the expected tosylate 3 by a mechanism that could involve neighbouring group participation of the nitro-substituent. In contrast, the isomeric alcohol 15 reacted normally with 4-toluenesulfonyl chloride giving the tosylate 16 under similar conditions. J. Heterocyclic Chem., 42, 1215Chem., 42, (2005.We have recently reported the preparation of a series of 5,6-dihydrobenzimidazo[2,1-a]isoquinoline derivatives 6 [1] and their corresponding N-oxide derivatives 5 [1,2] as part of a study of analogues of the anti-cancer agent Ellipticine (1) and its 9-oxygenated derivatives (Scheme 1) [1]. N-Oxides 5 were readily prepared by cyclodehydration of 2-(2-nitroaryl)-1,2,3,4-tetrahydroisoquinolines 2 in boiling propionic acid (the t-amino effect) [3] and deoxygenation of these compounds with phosphorus trichloride yielded derivatives of heterocyle 6 [1]. We were also interested in the preparation of the fully conjugated benzimidazo[2,1-a]isoquinolines 7 but the attempted oxidation of derivatives of heterocycles 6 were unsuccessful. Literature precedence suggested that this transformation might not be readily achieved because 2,3,9,10-tetramethoxybenzimidazo[2,1-a]isoquinoline had only been obtained in 10 % yield by palladium on carbon mediated dehydrogenation of the corresponding 5,6-dihydroderivative [4]. An alternative approach to these fully conjugated heterocycles was therefore sought.The strategy we envisaged was to prepare the 4-toluenesulfonate derivative 3 from which the enamine 4a might be obtained by base-induced elimination. Tautomerisation of this enamine might be then expected to yield the 6-methyl derivative 8 of compound 7 (Scheme 1). This note describes an unexpected reaction of the 4-toluenesulfonate derivative 3.The synthetic route to the 4-toluenesulfonate derivative 3 is shown in Scheme 2. 1,2,3,4-Tetrahydroisoquinoline-3-carboxylic acid (9) was reacted with 2-fluoronitrobenzene (10) and the resulting carboxylic acid was esterified directly by treatment with dimethyl sulfate under basic conditions giving the ester 11. Reduction of ester 11 was achieved by treatment with lithium borohydride in the presence of trimethoxyborane yielding the alcohol 12 [5]. When the alcohol 12 was treated with 4-toluenesulfonyl chloride in pyridine, unexpectedly, the chloride 13 was obtained. The formation of the chloride 13 has been rationalised as shown in Scheme 2 in which neighbouring group participation by the nitro-group results in a favourable 7-endo-tet intramolecular reaction [6] giving a putative cyclic intermediate that is then attacked by chloride yielding the product 13. Compound 13 could also be prepared by an alternative route by the reaction of alcohol Sep-Oct 2005 1215

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“…(e) The benzhydryl ester (7a) (see below) (3.8 g, 10 mmol) was catalytically hydrogenolysed in anhydrous ethanolic (50 ml) solution in the presence of a Pd-C catalyst (8%; 0.4 g) at ambient temperature and normal pressure (ca. 2 h) to give, after work-up, compound (8a) ( 4 Hz, respectively, CH2C02), 3.12 (d, J 2.5 Hz, 3-H), 3.89 (ddd, J9.1, 4.4, and 2.5 Hz, 2-H), 3.9-4.15 (m, OCH,CH,O), 6.1 (br s, exchangeable, NH), 6.91 (s, Ph,CH), and 7.28 (s, 2 x Ph).…”

Section: (2rs3sr)-3-( 2-methyl-13-dioxolan-2-yz)-4-oxoazetidin-2-ylac...mentioning

confidence: 99%

“…vmax~(film) 3 250, 1 760, 1 740br, 1 530, and 1 360 cm-'; 6, 2.61 and 3.16 (ABX system, Juem 14.8, Juic 2.5 and 5.1, 4 J 3 ~, ~~ 1.1 and 2.4 Hz, respectively, 3-H,), 2.86 and 3.00 (ABX system, Juem 18, Juic 8 and 5 Hz, respectively, CH,CO), 3.57 (s, COCH,CO,), 3.97 (dddd, J2.5,5.1,8 and 1 750,l 740,l 720,l 510,l 345, and 830 cm-'; 6, 2.55 and 3.10 CHZCO), 3.32 (d,J2.3 Hz,, 3.45 (s, COCH,COz), 3.79 (s, (ABX system,Joe,,,14.7,Juir 2.5 and 5.0,respectively;),2.66 and 2.97 (ABX system,Joe,,,17.5,Jvie 8.1 and 4.8 Hz,respectively,CH2CO),3.41 (s,COCH2CO),3.79(s,2 x MeO), 3.84(dddd,J 2.5,5.0,8.1,and 4.8 Hz,4.19 and 4.39 (AB system,J 14.8 Hz,NCH,Ar),5.03 (s,=CH,enol form),5.25 (s,OCH,Ar),2 x ArH, NCH,Ar group), 7.13 (d,J 8.8 Hz,ArH,NCH,Ar group),7.51 and 8.23 (AA'BB' system,J 8.6 Hz,4 x ArH, OCH,Ar group), and 11.7 (br s,enolic OH). This is in good agreement with the spectrum of the related N-dimethyl-tbutylsilyl) derivative obtained (by a different method) by Japanese scientists.…”

Section: (E)mentioning

confidence: 99%

Simple and condensed β-lactams. Part 5. The synthesis of some (5RS,6SR)-2-(2-formylaminoethylthio)-6-(2-methyl-1,3-dioxolan-2-yl)carbapenem-3-carboxylic acid derivatives and related compounds

Fetter¹,

Lempert²,

Gizur³

et al. 1986

J. Chem. Soc., Perkin Trans. 1

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Simple and condensed β-lactams-I

Cited by 18 publications

References 6 publications

A nitrilase-mediated entry to 4-carboxymethyl-β-lactams from chemically prepared 4-(cyanomethyl)azetidin-2-ones

A nitrilase-mediated entry to 4-carboxymethyl-β-lactams from chemically prepared 4-(cyanomethyl)azetidin-2-ones

Possible neighbouring group participation of a nitro-group in the conversion of 3-hydroxymethyl-2-(2-nitrophenyl)-1,2,3,4-tetrahydroisoquinoline into its 3-chloromethyl derivative

Simple and condensed β-lactams. Part 5. The synthesis of some (5RS,6SR)-2-(2-formylaminoethylthio)-6-(2-methyl-1,3-dioxolan-2-yl)carbapenem-3-carboxylic acid derivatives and related compounds

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