The penems, a new class of .beta.-lactam antibiotics. 2. Total synthesis of racemic 6-unsubstituted representatives

Lang, Marc; Prasad, Kapa; Holick, W.; Gosteli, J.; Ernest, I.; Woodward, R. B.

doi:10.1021/ja00515a024

Cited by 64 publications

(14 citation statements)

References 6 publications

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“…The discussed ylides are widely used for the synthesis of bicyclic β-lactam antibiotics. One of the earliest methods of synthesizing them, described by Woodward, consists in the treatment of the corresponding β-lactams 14 with glyoxylic acid esters [17][18][19][20][21][22] or their hemiacetals, 8,23,24 which yields the corresponding α-hydroxyglycine derivatives 15. The latter compounds react with thionyl chloride, followed by their reaction with triphenylphosphine in the presence of bases.…”

Section: Figurementioning

confidence: 99%

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α-Amino acid derivatives with a Cα-P bond in organic synthesis

Mazurkiewicz¹,

Kuźnik²,

Grymel³

et al. 2007

Arkivoc

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α-Amino acid derivatives with a C α -P bond have been used for a wide range of chemical transformations, including synthesis of many kinds of bioactive compounds, e.g. nonproteinogenic α-amino acids, α,β-dehydro-α-amino acids, dehydropeptides, β-lactam antibiotics and glycopeptides. The present review is focused on methods of synthesis of the title compounds, their properties and application in organic synthesis.

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Section: Figurementioning

confidence: 99%

“…The latter compounds react with thionyl chloride, followed by their reaction with triphenylphosphine in the presence of bases. β-Lactam antibiotics 16 derived from penem-3-carboxylic acid (Z = S) 8,19,23,24 and carbapenem-2-carboxylic acid (Z = CH) 21 were synthesized using this method (Scheme 6). …”

Section: Figurementioning

confidence: 99%

α-Amino acid derivatives with a Cα-P bond in organic synthesis

Mazurkiewicz¹,

Kuźnik²,

Grymel³

et al. 2007

Arkivoc

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“…5) using thiolates, allowed the synthesis of a range of thio-substituted penems from a common intermediate (126). A conceptually similar approach (127) enables the displacement of the phenolic leaving group in penems (86, R = CN) [85768- or (86, R = NO 2 ) [114707-30-1] using amines and thus provides a general route to 2-aminopenems (87) where R can be CH 3 or n-C 3 H 7 ; R can be H, CH 3 , CH 2 COOC 2 H 5 , or ; or both R and R can be .…”

Section: Modification Of Intact Penemsmentioning

confidence: 99%

Carbapenems and Penems

Southgate

Osborne

2000

Kirk-Othmer Encyclopedia of Chemical Technology

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In the period up to 1970 most β‐lactam research was concerned with the penicillin and cephalosporin group of antibiotics. Since that time, however, a wide variety of new mono‐ and bicyclic β‐lactam structures have been described. The carbapenems originated from natural sources; the penem ring and its derivatives are the products of the chemical synthetic approach to new antibiotics. The chemical names are: 7‐oxo‐( R )‐1‐azabicyclo[3.2.0]hept‐2‐ene‐2‐carboxylic acid, C 7 H 7 NO 3 , and 7‐oxo‐( R )‐4‐thia‐1‐azabicyclo[3.2.0]hept‐2‐ene‐2‐carboxylic acid, C 6 H 5 NO 3 S, respectively. Carbapenems include thienamycin (C 11 H 16 N 2 O 4 S), MM 4550 (C 13 H 16 N 2 O 9 S 2 ), MM 13902 (C 13 H 16 N 2 O 8 S 2 ), MM 17880 (C 13 H 18 N 2 O 2 S 2 ), PS‐5 (C 13 H 18 N 2 O 4 S), carpetimycin A (C 14 H 18 N 2 O 6 S), asparenomycin A (C 14 H 16 N 2 O 6 S), and pluracidomycin A (C 9 H 11 NO 10 S 2 ). Only S. cattleya and S. penemfaciens have been reported to give thienamycin. Thienamycin is isolated as a colorless, hygroscopic, zwitterionic solid. Carbapenems are extremely sensitive to many reaction conditions. Many derivatives of the amino, hydroxy, and carboxy group of thienamycin have been prepared primarily to study structure–activity relationships. One consequence of the discovery of the carbapenem natural products has been the development of new synthetic methods. Only chemical synthesis could provide the quantities of N ‐formimidoyl thienamycin (MK 0787) necessary for clinical trials and commercial production. A synthetic approach that involves the [3,4] bond formation using a carbene insertion reaction has been highly successful. A second method makes use of the lactone from acetone dicarboxylate. Thienamycin, the olivanic acids, and the majority of carbapenems are highly active broad‐spectrum antibiotics. Of the natural products, thienamycin is the most potent. Unlike carbapenems, no penems have been found in nature. The penem acid was shown to possess antibacterial activity in spite of its rather limited stability. Penems include SCH 29482 (C 10 H 13 NO 4 S 2 ), SCH 34343 (C 11 H 14 N 2 O 6 S 2 ), FCE 221201 (C 10 H 12 N 2 O 6 S), and others. 6‐Unsubstituted penems exhibit good activity against both gram‐positive and gram‐negative bacteria. Extensive carbapenem and penem antibiotic research has been ongoing since thienamycin was discovered in 1978. However, only the imipenem–cilastatin combination has become a commercial product. Meropenem was expected to be the second carbapenem on the market.

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“…50 In general, these penems are susceptible to cleavage by p-lactamases, although some activity versus ampicillin-resistant strains can be seen. The activities of these compounds stand in marked contrast to the inactive penicillanic acid (152) and cephalosporanic acid (153).…”

Section: >64 64mentioning

confidence: 99%