Antibiotics cascade reactions

The unselective 6jt-electrocyclization can be avoided with substrates that lack a [3-olefin substituent (Scheme 7.41).116 When chiral, nonracemic versions of these substrates are employed, Woerpel and Calad demonstrated that the cascade reaction efficiently transfers the chiral information. While silver salts were competent catalysts for the diastereoselective formation of silalactone 144 from 1301, on scale-up, copper(II) triflate proved to be more efficient. The authors attribute the poorer performance by silver to product inhibition. In eight steps, silalactone 144 was transformed into the antibiotic (+ Hyu-acetomycin, to further highlight the synthetic utility of the cascade process. 

When looking at polycyclic target structures like those of the tetracycline or anthracycline antibiotics, the most efficient syntheses rely on bicyclization approaches. They are especially impressive when they have been executed as cascade reactions forming more than two bonds at a time. In this context, the reader is referred to Muxfeldt s 1965 synthesis of tetracycline (Scheme 6.28) [117], the first example of this groundbreaking strategy. 

Halenaquinone and Halenaquinol have been isolated from a variety of sea sponges and have been shown to possess antibiotic, cardiotonic and protein tyrosine kinase inhibitory activity [37]. Kojima et al. have employed a number of novel palladium-catalyzed cascade reactions in the total synthesis of Halenaquinone and Halenaquinol (Scheme 7.18) [38]. First, P-alkyl Suzuki-Miyaura Coupling/... 

In a study on the synthesis of the antibiotic SF 2315B, the core structure of the natural product was assembled in stereocontrolled fashion by TBAF-induced autoxidation of a quinone (cf. 8 —> 9, Seheme 16), thereby forming three stereocenters and three C O bonds in a single operation [38]. A reaction cascade involving sequential oxygenation of an enol radical, cyclization and cleavage of the resultant endoperoxide accounts for this transformation [38]. 

In Nicolaou s synthesis of the bisanthraquinone antibiotic BE-43472B, he initiated a fascinating late-stage cascade by the reaction of a functionalized acyclic diene with a pentacyclic quinone dienophile. " In a highly complex example, Nakata performed the penultimate step in the synthesis of sarcophytoate by combining dienophile 121 and diene 122 in a thermal Diels-Alder reaction. 

Benzoxazine derivatives have been shown to possess pharmacological properties and 1,3-oxazine derivatives are widely known for their potential as antibiotics, antitumor compounds, analgesics, and anticonvulsants. In 2012, Bao and co-workers developed a novel and efficient synthesis of benzoxazine and 1,3-oxazine derivatives via a ligand-free copper(i)-catalyzed one-pot cascade addition-cyclization reaction (Scheme 3.72). A variety of carbo-diimides coupled with o-halophenylmethanols and/or substituted (Z)-3-iodoprop-2-en-l-ols to give the corresponding products in moderate to excellent yields under mild conditions. 

As exemplified by the macrolide antibiotic RK-397 (15, Scheme 14.4), proximal 1,3-arrays of hydroxyl-bearing stereogenic centers present the most prevalent structural phenotypes in a wide variety of polyketides [1]. Inspired by the cascade concept reported above, we desired a more direct synthesis to this structural synthon. As shown in Scheme 14.5, this involves the addition of a homo-allylic alcohol 5 to a suitable carbonyl compound 18, giving the corresponding hemi-acetal alkoxide (step 1). Formation of an electrophilic Jt-allyl complex (step 2) then results in the generation of intermediate 17, which finally undergoes an intramolecular allylic substitution reaction to the desired 1,3-allylic alcohols 16 in a suitably protected form (step 3). Notably, this sequence presents one of the first examples of hemiacetal alkoxides as nucleophiles in allylic substitution reactions. 

The problems of multiple prescribing in the elderly have been discussed in the context of a case of enalapril-associated dry cough misdiagnosed as pneumonia [34" ]. The prescribed antibiotics caused pseudomembranous colitis and an opioid-based syrup contributed to delirium. The authors drew attention to the effect of the prescribing cascade that can occur following the failure to identify an adverse drug reaction. 

A transannular aldol reaction is also part of the squa-rate ester cascade applied by Paquette and co-workers in their expeditious 10-step synthesis of hypnophilin, an antibiotic metabolite isolated from cultures of the fungus Pleurotellus hypnophilus. Sequential 1,2-additions of a pair of vinyl lithium reagents to the squarate ester 54 led to intermediates (i.e., 56 and 58) by either trans- or... 

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