The synthesis of a key intermediate of tricyclic beta-lactam antibiotics

Bismara, C.; Fabio, Romano Di; Donati, Daniele; Rossi, Tino; Thomas, Russell J.

doi:10.1016/0040-4039(95)00740-4

Cited by 32 publications

(14 citation statements)

References 5 publications

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“…Highly diastereoselective synthesis of a key intermediate (34) for the construction of the tricyclic carbapenem skeleton has been achieved by the reaction of acetoxyazetidin-2-one (17) with homochiral cyclohexenyl boranes (32), cyclohex-2-enyldimethylsilyl chloride (36), or racemic β-ketoester (38) (Fig. 4) [60,61,62].…”

Section: Construction Of the Tricyclic Carba-penem Skeletonmentioning

confidence: 99%

Current Status of Oral Carbapenem Development

Kumagai¹,

Tamai²,

Abé³

et al. 2002

CMCAIA

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Since the discovery of thienamycin (1) in 1976, many studies on the synthesis and structure-activity relationships of parenteral-use drugs have been done and several carbapenems, imipenem (2), panipenem (3), and meropenem (7), have been marketed. The development of oral carbapenems, however, is a fairly slow process because carbapenems are considered unstable in the stomach and intestine. Recently, several orally active carbapenems without stability problems have been developed as prodrug esters or prodrug peptides, including GV-118819 (12), CS-834 (13), L-084 (14), DZ-2640 (15), and peptidic derivatives of CL 191,121 (16). The active forms (35), (41), (44), (45), (16) of these prodrugs exhibited potent and well balanced antibacterial activities as well as resistance to renal dehydropeptidase-I. The pharmacokinetic parameters of compounds (12), (13), (14), and (15) after oral administration to healthy volunteers were reported. The half-life (t 1/2) of GV-118819 (12) was longer than that of the other compounds, while the Cmax, AUC and urinary excretion rate of L-084 (14) were higher than those of the others. In this review, the synthesis, chemical and biological properties, and pharmacokinetics of these oral carbapenems are described.

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Section: Construction Of the Tricyclic Carba-penem Skeletonmentioning

confidence: 99%

Current Status of Oral Carbapenem Development

Kumagai¹,

Tamai²,

Abé³

et al. 2002

CMCAIA

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“…21 More recent approaches, however, have both reduced the number of steps and improved the overall yields to key intermediates. Two approaches to olefin 24 published recently involve an intramolecular Sakurai reaction with a cyclohexenylsilane 23 (Scheme 3), and dialkylcyclohexenylboranes 24 and appropriate Lewis acids (Scheme 4). An even more direct approach to sanfetrinem is via the direct condensation of (2S)-methoxycyclohexanone with the 4-acetoxazetidinone 10.…”

Section: Trinemsmentioning

confidence: 99%

The renewed challenge of antibacterial chemotherapy†

Niccolai¹,

Tarsi²,

Thomas³

1997

Chem. Commun.

Self Cite

149

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We are currently witnessing a dramatic and alarming increase in the incidence of bacterial infections resistant to most common antibiotics. In this article, we examine briefly the background to this situation, and the mechanisms both of antibacterial action and bacterial resistance. Following this introduction is a discussion of the evolution of the various antibacterial classes and of the current approaches being adopted to keep at bay the threat of a return to a preantibiotic era.

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“…Glaxo S. p. A. laboratories ( Figure 1) had discovered a new family of β-lactam antibiotics having an additional 5, 6 or 7 membered ring fused to the 5-membered ring of the penem to provide tricyclic β-lactams known as trinems. [5] The tricyclic βlactams Sanfetrinem [6] (GV104326) and the pro-drug Sanfetrinem cilexetil [7] (GV118819) discovered by Glaxo laboratories have been found to possess a broad spectrum of antibacterial activities against both gram-positive and gram-negative aerobes and anaerobes, stability to clinically isolated βlactamases [8,9] and stability to human renal dehydropeptidases.…”

Section: Introductionmentioning

confidence: 99%

“…Due to this reason, the trinem GV104326 is clinically used as an antibiotic under the name GG-326. [9] Few more structural analogs of sanfetrinem were synthesized and are known to possess a broad spectrum of antibacterial activities. [7a] Some tricyclic β-lactams acted as inhibitors of β-lactamases [10][11][12] and other medicinally relevant mammalian enzymes implicated in many diseases.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of Chlorinated, Heteroatom‐Rich and Differently Fused Tricyclic β‐Lactams by Cu(I)‐Catalyzed Halogen Atom Transfer Radical Cyclization

Dawra¹,

Ram

Thakur

2020

ChemistrySelect

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The application of Cu (I)-catalyzed halogen atom transfer radical cyclization (ATRC) for the synthesis of two different series of chlorinated, heteroatom rich and differently fused tricyclic β-lactams has been demonstrated. N-substituted-3,4dihydropyrimidine-2(1H)-thiones synthesized by Biginelli reaction were used as starting materials for this synthetic pathway which upon S-allylation/alkylation furnished 2-allylthio/alkylthio-1,4-dihydropyrimidines (cyclic imines). Staudinger reaction of these cyclic imines with dichloroketene was employed to obtain the bicyclic dichloro-S-allyl/N-allyl-β-lactams, which upon subsequent Cu(I)-catalyzed ATRC produced two different series of tricyclic β-lactams. The difference in the relative behavior of N-allyl bicyclic dichloro-β-lactams and S-allyl bicyclic dichloro-β-lactams towards ATRC was also introspected in terms of their relative rates of cyclization, the amount of catalyst loading needed and the stabilities of tricyclic-β-lactams obtained after cyclization. To study the relative reactivity of Nallyl group and S-allyl group towards ATRC, the bicyclic dichloro-β-lactams having both S-allyl and N-allyl groups were synthesized. The intramolecular competitive experiments revealed the high reactivity of S-allyl group towards ATRC than the N-allyl group.[a] Dr. N. DawraMehr Chand Mahajan DAV College for Women Sector 36-A, Chandigarh,

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The synthesis of a key intermediate of tricyclic beta-lactam antibiotics

Cited by 32 publications

References 5 publications

Current Status of Oral Carbapenem Development

Current Status of Oral Carbapenem Development

The renewed challenge of antibacterial chemotherapy†

Synthesis of Chlorinated, Heteroatom‐Rich and Differently Fused Tricyclic β‐Lactams by Cu(I)‐Catalyzed Halogen Atom Transfer Radical Cyclization

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