Abstract:
:The synthesis of oxacephalotin and oxacephamandol, which are more active than natural, sulfur-containing congeners, and the isolation of clavulanic acid, a potent inhibitor of beta-lactamase enzymes, directed attention of many academic and industrial laboratories the synthesis of oxygen analogues of penicillins and cephalosporins. The present review focuses attention on the problem of stereocontrol in the formation of a desired configuration of the bridgehead carbon atom in the title compounds. Five feasible synthetic methods leading to the basic skeletons of clavams and 5-oxacephams are discussed. Three of them involve the nucleophilic substitution at C-4 of the azetidin- 2-ones performed as inter- or intramolecular process and the remaining two involve cycloaddition reactions between ketenes and iminoethers, or between vinyl ethers and isocyanates. Owing to the general application, stereospecificity and high asymmetric induction, the last method seems to be most advantageous. The weak point of the nucleophilic substitution methodology is that a nucleophile approaches the 3-substituted azetidin-2-one ring preferentially anti to the existing substituent and in the case where there is no substituent at C-3, that the stereoselectivity of formation of the new chirality center at C-4 is low. All discussed methods are illustrated by the examples taken from the literature.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Łysek R,Borsuk K,Furman B,Kałuza Z,Kazimierski A,Chmielewski Mdoi
10.2174/0929867043364883subject
Has Abstractpub_date
2004-07-01 00:00:00pages
1813-35issue
14eissn
0929-8673issn
1875-533Xjournal_volume
11pub_type
杂志文章,评审abstract::Insulin dependent diabetes mellitus (Type 1 diabetes, T1D) is a chronic autoimmune disorder characterized by the destruction of insulin-producing pancreatic beta cells by proinflammatory autoreactive T cells. In the past, several therapeutic approaches have been exploited by immunologists aiming to regulate the autoim...
journal_title:Current medicinal chemistry
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abstract::Whilst knowledge of basic biology, diagnosis and prognosis of glioblastoma (GB - WHO grade IV) are steadily improving, advancements of therapy are discouragingly slow, with the only significant novelty during last ten years represented by introduction of temozolomide in chemotherapy. In order to analyze the current st...
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abstract::Alzheimer's disease (AD) is a highly complex and rapidly progressive neurodegenerative disorder characterized by the systemic collapse of cognitive function and formation of dense amyloid plaques and neurofibrillary tangles. AD pathology is derived from the cholinergic, amyloid and tau hypotheses, respectively. Curren...
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abstract:BACKGROUND:Chronic, degenerative diseases are often characterized by inflammation and aberrant angiogenesis. For these pathologies, including rheumatoid arthritis, cardiovascular and autoimmune diseases, cancer, diabetes, and obesity, current therapies have limited efficacy. OBJECTIVES:The validation of novel (chemo)p...
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更新日期:2000-06-01 00:00:00
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abstract::We examined a large number of sudden infant death syndrome victims in order to point out a possible causal relationship between a previous hexavalent vaccination and the sudden infant death. We selected 110 cases submitted to in-depth histological examination of the autonomic nervous system and provided with detailed ...
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更新日期:2014-03-01 00:00:00
abstract::Tetracyclines (TCs) and their non-antimicrobial analogs (CMTs) have therapeutic potential to inhibit tissue destructive disease processes, such as cancer invasion and metastasis, by inhibiting certain matrix metalloproteinases. Enhanced matrix metalloproteinase-2 (MMP-2; gelatinase A) activity has been correlated to c...
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更新日期:2001-02-01 00:00:00
abstract:BACKGROUND:Hepatocellular Carcinoma (HCC) is one of the greatest global health burdens because of its uncontrolled cell growth and proliferation, aggressive nature as well as inherited chemoresistance. In spite of different treatment options currently available for HCC, the 5-year relative survival rates for HCC patien...
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abstract::The ionotropic P2X7 receptor (P2X7R) has become the focus of intense research interest for a number of reasons: i) it is a cation selective ion channel that is modulated by extracellular ATP. Upon stimulation by high concentrations of ATP it generates a non-selective membrane pore which is permeable to hydrophilic mol...
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abstract::Recent advances in endoscopic techniques such as capsule endoscopy have revealed that aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) often cause mucosal lesions not only in the upper gastrointestinal tract, but also in the small intestine in humans. Gastric and duodenal lesions caused by NSAIDs can be ...
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abstract:BACKGROUND:Since Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor which plays an important role in multiple aspects of cancer, including progression and migration, and it is constitutively activated in various human tumors, STAT3 inhibition has emerged as a validated strategy for the...
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abstract::N-BP, rapamycin and its derivatives have been originally developed respectively as anti-resorptive and anti-fungal agents. In fact, in vitro and in vivo experiments demonstrated that these compounds are multi-functional molecules exerting their effects on tumour cell growth and bone remodelling. The major challenge in...
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abstract::Hereditary amyloidogenic transthyretin (TTR) (ATTR) amyloidosis is an autosomal dominant form of fatal hereditary amyloidosis. Owing to progress in biochemical and molecular genetic analyses, this disease is now believed to occur worldwide. As of today, reports of about 120 different points of single or double mutatio...
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更新日期:2012-01-01 00:00:00
abstract::The efficacy of classical and molecular therapies in cancer is hampered by the occurrence of primary (intrinsic) and secondary (acquired) refractoriness of tumours to selected therapeutic regimens. Nevertheless, the increased knowledge of the genetic, molecular and metabolic mechanisms underlying cancer results in the...
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更新日期:2014-01-01 00:00:00
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abstract::Since photodynamic therapy emerged as a promising cancer treatment, the development of photosensitizers has gained great interest. In this context, the photosynthetic pigments, chlorophylls and bacteriochlorophylls, as excellent natural photosensitizers, attracted much attention. In effect, several (bacterio) chloroph...
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更新日期:2015-01-01 00:00:00