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Bicyclic β-lactams constitute an important class of fused-heterocyclic systems which have remained as an effective fighting tool against wide range of bacterial infections throughout 20th century. The importance of these molecules as versatile building blocks has grown exponentially in recent years. In this review, we shall discuss all the latest developments related to syntheses and reactions of bicyclic β-lactams in the last decade. This will provide useful and valuable information for understanding the behavior of bicyclic β-lactams for future development of synthetically/biologically relevant molecules. [Display omitted] [ABSTRACT FROM AUTHOR]

Total synthesis of THP tethered pyrone containing natural product cryptopyranmoscatone B2 was accomplished from commercially available 2-deoxyribose. The key THP unit was assembled by FeCl 3 catalyzed cyclization of an allyl alcohol. Brown allylation and RCM reactions were employed to construct the lactone unit. The synthesis represents the first total synthesis of the putative structure of the natural product. [ABSTRACT FROM AUTHOR]

A simple and efficient total synthesis of patulolide A from readily available 7-octen-1-ol is reported by asymmetric synthetic approach. The key reactions involved are asymmetric dihydroxylation using AD-mix-βand Grubbs’ ring-closing metathesis reaction for the synthesis macrocyclic ring system. [ABSTRACT FROM AUTHOR]

Herein we report the synthesis of 13-, 14- and 15-membered cyclic lactams, using Grubbs' RCM method in 25, 52 and 46% yields respectively. The cis-enamide functional group was successfully introduced into these cyclic lactams by syn sulfoxide elimination The synthetic cyclic lactams resemble natural cyclic peptides. Our synthetic methodology provides a simple route to making medium-sized cyclic lactams that could be used as models to mimic the β-turn in natural proteins, an important marker in understanding their biological activity. [ABSTRACT FROM AUTHOR]

We report the application of ring closing metathesis-based macrocyclization route for synthesizing 22–36 membered optically active aza-oxo crowns/polyether macrocycles. While the RCM-based synthesis of polyether macrocycles was well explored in the literature, the synthesis of optically active polyether macrocycles was not explored via the RCM reaction. Accordingly, the present method reveals an efficient assembling of a library of new classes of optically active aza-oxo polyether macrocycles from optically active RCM precursors, which were assembled from easily available linkers, chiral α-methylbenzylamine and amino alcohol building blocks under simple reaction conditions. [ABSTRACT FROM AUTHOR]

A new synthetic strategy directed towards the solomonamides, a novel class of cyclopeptides of marine origin, has been developed utilizing an olefin metathesis reaction to form the [15]-membered ring contained in these natural products. We demonstrated the efficiency and validity of this synthetic approach for the construction of the macrocyclic core of the solomonamides in a minimally oxidized system. In fact, the olefin metathesis cyclization proceeded in a stereoselective manner to provide exclusively the Z -isomer in high yield. The described synthetic strategy for the solomonamides allows for access to the natural products, as well as offering the opportunity for the generation of a diverse set of analogues in the subsequent oxidation phase. [ABSTRACT FROM AUTHOR]

The synthesis of enantiomerically enriched 7- and 8-hydroxystearic acids (7- and 8-HSA) has been successfully accomplished starting from chiral nonracemic 1-pentadecen-4-ol and 1-tetradecen-4-ol, respectively. Their Yamaguchi's esterification with 4-pentenoic and 5-hexenoic acids, respectively, afforded the suitable dienic esters which were submitted to ring-closing metathesis reaction. After hydrogenation and basic hydrolysis of the complex reaction mixture, chiral nonracemic 7- and 8-HSA were obtained in about 40% total yield. [ABSTRACT FROM AUTHOR]

An efficient and common method for the synthesis of 5a-carba-α- d -mannopyranose 5 , 5a-carba-β- d -mannopyranose 6 , (+) methyl shikimate 9 , (+) methyl-5- epi -shikimate 10 , validamine analogue 15 and valiolamine analogue 16 from d -mannose, formal synthesis of Tamiflu 17 from d -ribose and also synthesis of 5a-carba-α- d -glucopyaranose 1 , 5a-carba-β- d -glucopyaranose 2 , 5a-carba-β- l -altropyranose 7 and 5a-carba-α- l -altropyranose 8 from d -xylose is described using Nozaki–Hiyama–Kishi (NHK) condition and ring closing metathesis (RCM). In this transformation 5-deoxy-5-halo-manno/ribo/xylo furanoside undergoes reductive elimination in the presence of Mn/CrCl 3 to give corresponding olefin-aldehyde which was trapped by nucleophile under the same condition to afford diolefinic species which on metathesis reaction with appropriate Grubbs catalyst produced required carbocycles. [ABSTRACT FROM AUTHOR]

A convenient route leading to variously substituted N-alkyl-N'-aryl-o-phenylenediamine derivatives via quaternization of the imine nitrogen atom of 2-(arylamino)arylimino-phosphoranes is presented. The method allows to introduce identical or different alkyl groups onto both nitrogen atoms. The N,N'-bis-allyl derivatives so obtained, after protecting the secondary amine group, easily undergo RCM cyclization providing unsymmetrically substituted 1,2,5,6-tetrahydro-1,6-benzodiazocine systems in high yields. [ABSTRACT FROM AUTHOR]

Ring closing metathesis (RCM) reactions of suitable substrates having terminal olefins, which are assembled from various linkers and hydroxy benzaldehydes and syntheses of a wide range of 16–30 membered, new crown ether-type polyether, aza-polyether, bis aza-polyether macrocycles and dilactone moiety embedded polyether macrocycles (macrolides) are reported. After the ring-closure reaction, installation of different functional groups and functional group modification on the periphery of the synthesized polyether/crown ether macrocycles obtained in the RCM reactions are accomplished using the epoxidation, oxidation and catalytic hydrogenation-based synthetic transformations. Along this line, the syntheses of a variety of polyether macrocycles possessing epoxide or α-hydroxy ketone or 1,2-diol functionalities at the periphery have been shown. Furthermore, the synthesized α-hydroxy ketone functionality installed polyether macrocycles were subjected to the allylation and Reformatsky type reactions to obtain homoallyl alcohol moiety-based and lactone ring-appended polyether macrocycles. [ABSTRACT FROM AUTHOR]

We report a newly developed synthesis of a number of alditol thiacrowns using an eco-friendly and versatile two-step strategy: the regioselective thioallyletherification of a polyhydroxylated alditol followed by a ring closing metathesis using the Grubbs second generation catalyst. This approach allows a series of target thiacrown products to be obtained in acceptable to good yields, from the corresponding α,ω-dithioallylether alditol starting materials featuring either the xylo , ribo , threo , erythro , d - manno or d - gluco configurations. The per- O -acetylated d -mannitol dithioallyether 10 , easily obtained on a large scale using this approach, was selected for evaluation as both an antibacterial and an antioxidant. Although no antibacterial activity was observed for the bacterial strains investigated, compound 10 is shown to be an antioxidant, and able to quench hydrogen peroxide in a stoichiometric fashion. [ABSTRACT FROM AUTHOR]

Abstract: Several analogues of the fungal natural product aigialomycin D (AmD) have been synthesised. These include the stereoisomer 5′R,6′S-AmD, 2,4-di-deoxyAmD, 1′,2′,7′,8′-tetrahydroAmD and a 15-membered macrocyclic sulfone. Growth inhibitory activities of these compounds against the HL-60 leukaemic cell line were measured. The ring-expanded sulfone and tetrahydro-analogue were found to have similar IC50 values to the natural product, whereas the 5′R,6′S-stereoisomer was inactive. Energy minimisation of AmD and the synthesised analogues resulted in a range of lowest energy conformers, from planar, open arrangements of the macrocycle in AmD and tetrahydroAmD to bent, L-shaped structures for the sulfone. The synthesis of methyl orsellinate was investigated and optimised as part of this work. A stereodivergent route to both enantiomers of the diol fragment from d-ribose was also achieved. [Copyright &y& Elsevier]

The identification of synthesizable substructural domains within more complex structural targets is of significant value in designing a workable plan of synthesis. We term this process "pattern recognition analysis" (PRA). In this paper we continued to build on the theme of PRA as a potential resource in retrosynthetic blueprints to reach highly challenging targets. The paper operates at two levels. First, there is provided a clear sense of definitions of categories by which patterns are related to hypothetical reaction types. Although the required reaction type may for the moment not exist, we believe that this method of analysis is likely to promote innovation that identifies unmet needs and opportunities to advance the cause of complex target synthesis. In addition, we describe reductions to practice in expanding the menu of achievable patterns. It is likely that the future value of PRA will be associated with its utility in leading the way to new and exploitable chemical innovation. [ABSTRACT FROM AUTHOR]

Abstract: The reaction of amino hexahydro-s-indacene with glyoxal, reduction of the diimine to the diamine and cyclization with HC(OEt)3 yields the new 1,3-bis(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-4,5-dihydro-1H-imidazol-3-ium chloride 3· HCl with conformationally restricted alkyl groups ortho to the heterocyclic substituent. Reaction of 3· HCl with Ag2O gave the respective silver NHC complex (yield 78%), which was used to synthesize the respective (3)IrCl(cod) (yield 86%), whose reaction with CO gave (3)IrCl(CO)2 6 (yield 98%). The Grubbs II type complex [(3)RuCl2(PCy3)(3-phenyl-indenylid-1-ene)] was synthesized (yield 68%) and converted into [(3)RuCl2(py)(3-phenyl-indenylid-1-ene)] (yield 78%) in pyridine solvent. With this complex the respective Grubbs–Hoveyda species (yield 68%) and two bisNHC complexes [(3)(NHCewg)RuCl2(3-phenyl-indenylid-1-ene)] (yield 87%, 89%) were obtained. The stereoelectronic properties of the new NHC ligand were determined employing IR spectroscopy, cyclic voltammetry and buried-volume analysis based on the crystal structure of complex 6. The activity of the ruthenium complexes in RCM reactions of sterically hindered substrates was tested. [Copyright &y& Elsevier]

Abstract: A simple and divergent route for the total synthesis of pericosine B and pericosine C and their enantiomers from d-ribose by using the Baylis–Hillman reaction and ring-closing metathesis reactions as key steps has been described. [Copyright &y& Elsevier]

Abstract: The compact synthesis of a new ring fused benzo[b]thieno derivative with an embedded nine-membered ring system via ring closing metathesis methodology is described. The preparation of the novel 11H-benzo[b]thieno[2,3-c]pyrrolo[2,3-a]indol-11-one via palladium-mediated oxidative cyclisation of benzo[b]thien-2-oyl indole derivatives is also reported. [Copyright &y& Elsevier]

Abstract: A ring closing metathesis approach has been used to prepare a novel range of indoles 1,7-annulated with nitromethyl and lactone functionalised medium-sized rings. Initial studies into the preparation of lactam functionalised rings are also discussed. [Copyright &y& Elsevier]

Abstract: A concise total synthesis of 11-O-methyldebenzoyltashironin is reported in which oxidative dearomatization-IMDA-RCM triad constitutes the key ring forming steps, while an unorthodox DIBAL-H mediated stereo- and regioselective reductive epoxide openings and implementation of the vinyl bromide–carbonyl equivalency concept were pivotal to the success of this endeavor. [Copyright &y& Elsevier]

Abstract: Stereoselective total synthesis of decarestrictine-J, a polyketide natural product is described. The synthesis involves the Prins cyclisation and Ring Closing Metathesis (RCM) as key steps. [Copyright &y& Elsevier]

Total synthesis of styryl lactone natural products cryptomoscatone D1, D2, and (5 R ,7 S )-kurzilactone has been accomplished in good yield from commercial available trans -cinnamaldehyde. The key steps involved in these syntheses are Mukaiyama aldol reaction, diastereoselective reduction, Brown’s allylation, and ring closing metathesis. [ABSTRACT FROM AUTHOR]

Abstract: The first total synthesis of 9-membered macrolide, stagonolide-F (3), starting from commercially available 1,5-pentane diol is reported. A combination of Jacobsen’s hydrolytic kinetic resolution (HKR) and Sharpless epoxidation is used for the creation of two stereogenic centers, while ring-closing metathesis (RCM) strategy was used for the construction of the lactone ring. The molecule synthesized exhibited potent antifungal, antibacterial and cytotoxic activities against all the tested strains. [Copyright &y& Elsevier]

Abstract: Nitroalkenes derived from O-protected salicylaldehyde undergo facile Michael-type addition of nucleophiles possessing unsaturated tether. Ring closing metathesis of the Michael adducts provides benzo-fused medium ring cyclic ethers possessing a nitroalkyl functionality. [Copyright &y& Elsevier]

Abstract: The stereoselective total synthesis of tarchonanthuslactone, a polyketide natural product, has been achieved. The synthesis exploits the high stereochemical control in the Prins cyclisation along with ring closing metathesis (RCM) as a key step. [Copyright &y& Elsevier]

Abstract: A preliminary study dealing with the feasibility of ring closing metathesis and ene-yne ring closing metathesis to construct the central bicyclic cores of uprolides D and E was investigated. [Copyright &y& Elsevier]

Abstract: The central macrocyclic core of the macrocidins was constructed using RCM as the key reaction. A preliminary investigation dealing with the key reactions, that is, the Dieckmann cyclization and the RCM, revealed that RCM of the β-ketoamide is better than RCM of the corresponding acyltetramic acid. [Copyright &y& Elsevier]

Abstract: A seteroselective total synthesis of (+)-boronolide is described. The key steps are Sharpless asymmetric dihydroxylation, Shibasaki''s asymmetric Henry reaction, asymmetric allylation and ring closing metathesis. [Copyright &y& Elsevier]

Abstract: Ring closing metathesis of the appropriate 1,ω-dienes led to efficient synthetic approaches towards the corresponding macrocyclic polyoxadiamides and tetraamides with 18–40 membered ring sizes in good to excellent yields using Grubbs'' catalyst. [Copyright &y& Elsevier]

The synthesis of bicyclic 3,8-secotaxane diterpenoids, which includes Taxuspine U and X, has been achieved through an approach that involves a ring closing metathesis reaction as key step for the macrocycle formation. [Copyright &y& Elsevier]

Using ring closing metathesis (RCM) as the key operation, a rapid access to β-lactams fused to a sultam moiety of variable ring size was developed from low cost, commercially available starting materials. An efficient RCM of 4-vinyl-azetidin-2-ones to give 1-aza-bicyclo[4.2.0]oct-4-en-8-ones is also reported. [Copyright &y& Elsevier]

The preparation of a new ring F building block for the marine polyether toxins, the ciguatoxins, employing ascorbic acid as a chiral pool starting material, is reported. [Copyright &y& Elsevier]

Abstract: A short synthesis of Hagen’s gland lactones 1 and 2 from commercially available pentanal and heptanal, respectively, is outlined. The approach relies on sequential ring closing metathesis and intramolecular oxy-Michael addition as the key transformations. [Copyright &y& Elsevier]

Abstract: A stereoselective total synthesis of xyolide is described employing MacMillan α-hydroxylation, Steglich esterification, and ring closing metathesis as key steps. The use of organocatalytic MacMillan α-hydroxylation to construct two of the chiral centers of the xyolide makes this approach attractive. [Copyright &y& Elsevier]

Abstract: A convergent and highly stereoselective total synthesis of the Z-isomer of cytospolide E has been achieved via Evan’s aldol reaction, Sharpless kinetic resolution and RCM cyclisation. [Copyright &y& Elsevier]

Abstract: Asymmetric total synthesis of small ring macrolide stagonolide-E has been described in this communication. The main highlight of our synthetic strategy is the application of ME-DKR (metal enzyme combo dynamic kinetic resolution) reaction, asymmetric reduction with Noyori’s BINAL-H reagent system, stereoselective cross metathesis, and RCM (ring closing metathesis) reaction at a late stage enables us to achieve the synthesis of the target molecule in an efficient way. [Copyright &y& Elsevier]

Abstract: A microwave-promoted three-step tandem process for the synthesis of bicyclic γ-lactams is developed. In all cases examined this led to significantly faster tandem processes producing the bicyclic γ-lactams more cleanly and reproducibly compared to standard thermal conditions. [Copyright &y& Elsevier]

Abstract: A practical stereoselective synthesis of (6S)-5,6,dihydro-6-[(2R)-2-hydroxy-6-phenyl hexyl]-2H-pyran-2-one (1), a potent natural antifungal compound, is described. The sequence involves diastereoselective iodine-induced electrophilic cyclization, epoxide ring opening with a vinyl Grignard reagent and ring closing metathesis (RCM) as the key steps. [Copyright &y& Elsevier]

Huperzine B and its analogues were obtained through ring closing metathesis of N-alkenyl amine to the corresponding tricyclic compounds. [Copyright &y& Elsevier]

Ring closing metathesis (RCM) has emerged as a powerful tool to construct macrocyclic ring systems. However, the product distribution of monomer and oligomers is often a problem in the formation of medium to large rings. In the course of synthetic studies on the natural product radicicol and its analogs, we have found that the reaction temperature, along with concentration, has significant impact on the outcome of the product ratio. Specifically, carrying out the RCM reaction in refluxing toluene (110°C) at higher dilution affords improved yields of the monomeric macrocycle. Similar observations for another family of macrolactone natural products, the epothilones, are also reported. [Copyright &y& Elsevier]

A short and efficient synthesis of [7R,6S,5S,4R]-triacetoxy-(−)-goniotriol starting form d-glucose is described. A sequence of ring closing metathesis (RCM) followed by a PCC oxidation was used to construct the core six-membered α,β-unsaturated lactone moiety. [Copyright &y& Elsevier]

The RCM metathesis reaction catalyzed by Grubbs’ ruthenium catalyst is used with a series of 1,2-disubstituted indoles leading with excellent yields to tricyclic compounds. When applied to 1-allyl-2-vinylindoles this methodology allows a new entry to the mitosene skeleton. [Copyright &y& Elsevier]

Abstract: An expedient synthesis of bruguierol A encompassing a novel 2,3-benzo-8-oxabicyclo[3.2.1]octane ring system is described employing ring closing metathesis to generate the oxa-bridged tricyclic core. [Copyright &y& Elsevier]