同: beta-lactams

-beta-lactam

WordNet

to remain unmolested, undisturbed, or uninterrupted -- used only in infinitive form; "let her be"
work in a specific place, with a specific subject, or in a specific function; "He is a herpetologist"; "She is our resident philosopher" (同)follow
have life, be alive; "Our great leader is no more"; "My grandfather lived until the end of war" (同)live
be identical to; be someone or something; "The president of the company is John Smith"; "This is my house"
happen, occur, take place; "I lost my wallet; this was during the visit to my parents house"; "There were two hundred people at his funeral"; "There was a lot of noise in the kitchen"
have the quality of being; (copula, used with an adjective or a predicate noun); "John is rich"; "This is not a good answer"
occupy a certain position or area; be somewhere; "Where is my umbrella?" "The toolshed is in the back"; "What is behind this behavior?"
spend or use time; "I may be an hour"
stake on the outcome of an issue; "I bet $100 on that new horse"; "She played all her money on the dark horse" (同)wager, play
the act of gambling; "he did it on a bet" (同)wager
maintain with or as if with a bet; "I bet she will be there!" (同)wager
second in order of importance; "the candidate, considered a beta male, was perceived to be unable to lead his party to victory"
the 2nd letter of the Greek alphabet
preliminary or testing stage of a software or hardware product; "a beta version"; "beta software"
beets (同)genus Beta

PrepTutorEJDIC

《連結語として補語を伴なって…『である』,…だ,…です / 《位置・場所を表す語句を伴って》(…に)『ある』,いる(occupy a place or situation) / 〈物事が〉『存在する』,ある(exist);〈生物が〉生存する,生きている(live) / 行われる,起こる,発生する(take place, occur) / 存続する,そのままでいる(remain as before) / 《『be to』 do》 / …する予定である,…することになっている / …すべきだ / 《受動態の不定詞を伴って》…できる / 《命令》…するのだ / 《条件節に》…する意図がある / 《『if…were to』 do》…するとしたなら / 《『be』 do『ing』》《進行形》 / 《進行中の動作》…している,しつつある / 《近い未来》…しようとしている,するつもり / 《動作の反復》(いつも)…している / 《『be』+『他動詞の過去分詞』》《受動態》…される,されている / 《『be』+『自動詞の過去分詞』》《完了形》…した[状態にある]
『かけ』・(…との)かけ《+『with』+『名』》 / かけた物(金) / かけの対象 / 〈金・物〉'を'『かける』 / (かけ事・ゲームなどで)〈人〉‘と'『かけをする』《+『名』〈人〉+『on』+『名』》 / (…に)『かける』《+『on』(『against』)+『名』(one's do『ing』)》
ベータ(ギリシア語アルファベットの第2文字;B,β;英語のB,b に遭当)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/10 02:16:52」(JST)

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A β-lactam (beta-lactam) ring is a four-membered lactam.^[1] (A lactam is a cyclic amide). It is named as such because the nitrogen atom is attached to the β-carbon relative to the carbonyl. The simplest β-lactam possible is 2-azetidinone.

Clinical significance

Penicillin core structure

The β-lactam ring is part of the core structure of several antibiotic families, the principal ones being the penicillins, cephalosporins, carbapenems, and monobactams, which are, therefore, also called β-lactam antibiotics. Nearly all of these antibiotics work by inhibiting bacterial cell wall biosynthesis. This has a lethal effect on bacteria. Bacteria do, however, contain within their populations, in smaller quantities, bacteria that are resistant against β-lactam antibiotics. They do this by expressing one of many β-lactamase genes. More than 1,000 different β-lactamase enzymes have been documented in various species of bacteria.^[2] These enzymes vary widely in their chemical structure and catalytic efficiencies.^[2] When bacterial populations have these resistant subgroups, treatment with β-lactam can result in the resistant strain becoming more prevalent and therefore more virulent.

History

The first synthetic β-lactam was prepared by Hermann Staudinger in 1907 by reaction of the Schiff base of aniline and benzaldehyde with diphenylketene^[3]^[4] in a [2+2] cycloaddition:

Up to 1970, most β-lactam research was concerned with the penicillin and cephalosporin groups, but since then, a wide variety of structures have been described.^[5]

Synthesis

The Breckpot Synthesis

The synthesis of substituted β-lactams from the cyclization of beta amino acid esters using the Grignard reagent [1]

Breckpot Synthesis

Nomenclature

The β-lactam core structures. (A) A penam. (B) A carbapenam. (C) An oxapenam. (D) A penem. (E) A carbapenem. (F) A monobactam. (G) A cephem. (H) A carbacephem. (I) An oxacephem.

β-Lactams are classified according to their core ring structures.^[6]

β-Lactams fused to saturated five-membered rings:
- β-Lactams containing thiazolidine rings are named penams.
- β-Lactams containing pyrrolidine rings are named carbapenams.
- β-Lactams fused to oxazolidine rings are named oxapenams or clavams.
β-Lactams fused to unsaturated five-membered rings:
- β-Lactams containing 2,3-dihydrothiazole rings are named penems.
- β-Lactams containing 2,3-dihydro-1H-pyrrole rings are named carbapenems.
β-Lactams fused to unsaturated six-membered rings:
- β-Lactams containing 3,6-dihydro-2H-1,3-thiazine rings are named cephems.
- β-Lactams containing 1,2,3,4-tetrahydropyridine rings are named carbacephems.
- β-Lactams containing 3,6-dihydro-2H-1,3-oxazine rings are named oxacephems.
β-Lactams not fused to any other ring are named monobactams.

By convention, the bicyclic β-lactams are numbered starting with the position occupied by sulfur in the penams and cephems, regardless of which atom it is in a given class. That is, position 1 is always adjacent to the β-carbon of β-lactam ring. The numbering continues clockwise from position one until the β-carbon of β-lactam is reached, at which point numbering continues counterclockwise around the lactam ring to number the remaining to carbons. For example, the nitrogen atom of all bicyclic β-lactams fused to five-membered rings is labelled position 4, as it is in penams, while in cephems, the nitrogen is position 5.

The numbering of monolactams follows that of the IUPAC; the nitrogen atom is position 1, the carbonyl carbon is 2, the α-carbon is 3, and the β-carbon 4.

Reactivity

Due to ring strain, β-lactams are more reactive to hydrolysis conditions than are linear amides or larger lactams. This strain is further increased by fusion to a second ring, as found in most β-lactam antibiotics. This trend is due to the amide character of the β-lactam being reduced by the aplanarity of the system. The nitrogen atom of an ideal amide is sp²-hybridized due to resonance, and sp²-hybridized atoms have trigonal planar bond geometry. As a pyramidal bond geometry is forced upon the nitrogen atom by the ring strain, the resonance of the amide bond is reduced, and the carbonyl becomes more ketone-like. Nobel laureate Woodward described a parameter h as a measure of the height of the trigonal pyramid defined by the nitrogen (as the apex) and its three adjacent atoms. h corresponds to the strength of the β-lactam bond with lower numbers (more planar; more like ideal amides) being stronger and less reactive.^[7] Monobactams have h values between 0.05 and 0.10 angstroms (Å). Cephems have h values in of 0.20–0.25 Å. Penams have values in the range 0.40–0.50 Å, while carbapenems and clavams have values of 0.50–0.60 Å, being the most reactive of the β-lactams toward hydrolysis.^[8]

Other applications

A new study has suggested that β-lactams can undergo ring-opening polymerization to form amide bonds, to become nylon-3 polymers. The backbones of these polymers are identical to peptides, which offer them biofunctionality. These nylon-3 polymers can either mimic host defense peptides or act as signals to stimulate 3T3 stem cell function.^{[citation needed]}

Antiproliferative agents that target tubulin with β-lactams in their structure have also been reported.^[9]^[10]

References

^ Gilchrist, T. (1987). Heterocyclic Chemistry. Harlow: Longman Scientific. ISBN 0-582-01421-2.
^ ^a ^b Ehmann, David E. et al. (2012). "Avibactam is a covalent, reversible, non-β-lactam β-lactamase inhibitor". PNAS 109 (29): 11663–11668. doi:10.1073/pnas.1205073109.
^ Tidwell, Thomas T. (2008). "Hugo (Ugo) Schiff, Schiff Bases, and a Century of β-Lactam Synthesis". Angewandte Chemie International Edition 47 (6): 1016–20. doi:10.1002/anie.200702965. PMID 18022986.
^ Hermann Staudinger (1907). "Zur Kenntniss der Ketene. Diphenylketen". Justus Liebigs Ann. Chem. 356 (1-2): 51–123. doi:10.1002/jlac.19073560106.
^ Flynn, E.H. (1972). Cephalosporins and Penicillins : Chemistry and Biology. New York and London: Academic Press.
^ Dalhoff, A.; Janjic, N.; Echols, R. (2006). "Redefining penems". Biochemical Pharmacology 71 (7): 1085–1095. doi:10.1016/j.bcp.2005.12.003. PMID 16413506. edit
^ Woodward, R.B. (1980). "Penems and related substances". Phil Trans Royal Soc Chem B 289 (1036): 239–50. doi:10.1098/rstb.1980.0042.
^ Nangia, A.; Biradha, K.; Desiraju, G.R. (1996). "Correlation of biological activity in β-lactam antibiotics with Woodward and Cohen structural parameters: A Cambridge database study". J Chem Soc, Perkin Trans 2 (5): 943–53. doi:10.1039/p29960000943.
^ O'Boyle, Niamh; Miriam Carr; Lisa Greene; Orla Bergin; Seema M. Nathwani; Thomas McCabe; David G. Lloyd; Daniela M. Zisterer; Mary J. Meegan (December 2010). "Synthesis and Evaluation of Azetidinone Analogues of Combretastatin A-4 as Tubulin Targeting Agents". Journal of Medicinal Chemistry 53 (24): 8569–8584. doi:10.1021/jm101115u. PMID 21080725.
^ O'Boyle, Niamh; Lisa Greene; Orla Bergin; Jean-Baptiste Fichet; Thomas McCabe; David G. Lloyd; Daniela M Zisterer; Mary J. Meegan (2011). "Synthesis, evaluation and structural studies of antiproliferative tubulin-targeting azetidin-2-ones". Bioorganic and Medicinal Chemistry 19 (7): 2306–2625. doi:10.1016/j.bmc.2011.02.022.

External links

Synthesis of β-lactams

UpToDate Contents

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1. β-ラクタム系抗生物質：作用機序、耐性および有害作用 beta lactam antibiotics mechanisms of action and resistance and adverse effects
2. βラクタム系抗生物質の長期注入投与 prolonged infusions of beta lactam antibiotics
3. β-ラクタム系抗菌薬に対する肺炎レンサ球菌の耐性 resistance of streptococcus pneumoniae to beta lactam antibiotics
4. ペニシリン penicillins
5. β-ラクタマーゼ阻害剤、カルバペネム系、およびモノバクタム系抗菌薬の併用 combination beta lactamase inhibitors carbapenems and monobactams

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This work presented a highly sensitive bacterial antibiotic susceptibility test through β-lactamase assay using Parylene-matrix chip. β-lactamases (EC 3.5.2.6) are an important family of enzymes that confer resistance to β-lactam antibiotics by catalyzing the hydrolysis of these antibiotics. Here
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The Science of the total environment.Sci Total Environ.2015 Sep 1;526:366-73. doi: 10.1016/j.scitotenv.2015.05.046. Epub 2015 May 16.
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