Macrocyclization tandem

This example should not have appeared in this review, because a templating ring is already present nevertheless, it conveniently permits the introduction of Patten-den s macrocyclization tandem transannulation strategy E. 

Nau WM, Ghale G, Hennig A et al (2009) Substrate-selective supramolecular tandem assays monitoring enzyme inhibition of arginase and diamine oxidase by fluorescent dye displacement from calixarene and cucurbituril macrocycles. J Am Chem Soc 131 11558-11570... 

Enantioseparation of nine amphetamine derivatives, methorphan, and propoxyphene was studied by comparing two different CSP typologies, a macrocyclic antibiotic CSP (vancomycin) and a native P-cyclodextrin CSP [123]. The suitability of the eluent systems to ESI interfacing was discussed, and a tandem mass spectrometric (MS/MS) detection method was developed. 

Ramos, L. et al., Liquid chromatographic/atmospheric pressure chemical ionization tandem mass spectrometry enantiomeric separation of DL-fhreo-methylphenidate (Ritalin ) using a macrocyclic antibiotic as the chiral selector. Rapid Commun. Mass Spectrom., 13, 2054, 1999. 

Silver carbonate, when used as the base in the dehydrochlorination of hydrazonyl chlorides, has a unique effect in enhancing yields and favoring particular modes of reaction, for example, in the promotion of the tandem intermolecular-intramolecular synthesis of macrocycles 302 discussed in Section 7.3.2.4 (73). Such differences have led to some investigations into the mechanism of its reaction. In this work (74), the hydrazonyl chloride 134 was reacted with 2 M equiv of silver carbonate in the presence of various allylic alcohols. 

Extension of the linkage to hve atoms as in 285 provides routes to pyrazolines or pyrazoles 286, or 1,2,4-triazoles 287, fused to a seven-membered ring. The products are potentially biologically active and examples have been reported for X=N (177-181), X = 0 (181-185) and for a pyrazolo fused analogue (186) and X = S (187). In some cases, [e.g., (183)], these reactions are accompanied by tandem intramolecular-intermolecular reactions leading to the formation of macrocycles (see the section Tandem Intermolecular-Intramolecular Cycloaddition Reactions). 

The addition of thiyl radicals to alkenes or alkynes to initiate tandem sequences has also been explored. A highly stereo-controlled phenyl thiyl radical addition, 10-endo macrocyclization, termination process has been used to furnish the macrocycle (37) from the dimethylacrylic ester (36).48 In other work the vinyl radical (38) fonned from addition of a thiyl radical to an enyne gives a mixture of the three products (39)-(41) formed either by 6-exo cyclization (39), addition into the aromatic ring followed by trapping with AIBN (40), or rearomatization and fragmentation to give the sulfide (41) (Scheme 15).49... 

Zhu et al. [103] reported a fadle access to biologically relevant macrocycles bearing an endo diaryl ether bond by means of a tandem Ugi-4CR/SNAr. The reaction between 3-hydroxyphenylacetic [or 3-(3-hydroxyphenyl)propionic] acid, aldehydes, amines, and isocyanide 197 gave the expected dipeptide derivatives 198 as a 1 1 mixture of diastereoisomers. The reaction gave high yields when performed in tri-... 

Banfi and co-workers have also employed similar methodology to access meso-cyclic yS-turn scaffolds by the tandem U-MCR/RCM procedure generating such macrocyclic structures as 87 [73]. 

With respect to this, Ellman and coworkers [16], Zhu and coworkers [17], Amusch and Pieters [18], and Liskamp and coworkers [19] have prepared (monocyclic) mimics of the D-E part of the cavity of these antibiotics via an intramolecular nucleophilic aromatic substitution [16-18] or a Sonogashira-based macrocyclization [19] (Figure 1.4). Recently, a bicydic mimic of the C-D-E cavity, which was prepared by a Stille reaction followed by tandem ring-dosing metathesis (9, Figure 1.4), was described by liskamp and coworkers [20]. Considerable challenges lie ahead for the synthetic chemist in order to develop practical syntheses of mimics of vancomydn capable of binding not only D-Ala-D-Ala, but also cell wall parts of resistant bacteria, i.e. D-Ala-D-lactate. 

Scheme 16 Structural diversity of macrocycles by tandem Ugi-[3+2] cycloaddition process...

Titanium(rv)-mediated tandem deprotection-cyclodehydration of a protected cysteine A -amide was used in the synthesis of thiazolone- and thiazole-containing heterocycles as building blocks for macrocycle synthesis <20000L3289>. Similarly, the directly connected thiazole-oxazole ring system present in microcin B17 was synthesized from aminoacetonitrile hydrochloride <1996JOC778>. 

Cyclic ketones. 1,5-Dienes undergo silylcarbonylation and cyclization in tandem in the presence of CO. Macrocyclic ketolactones are acquired from (o-iodoalkyl acrylates by an intramolecular radical Michael reaction under similar conditions. 

Suzuki coupling has been used in tandem with Stille coupling. The boronic ester analog of (44) has been coupled to provide (46g).49 Similarly, the boronic ester (48) was coupled with (45b) to afford (49), which then was coupled with an analogous diiodo-derivative to give a shape-persistent bis-tpy macrocycle (Scheme 8). 0... 

The original tandem Claisen rearrangement promoted by Et2AlCl and 2-methyl-2-butene was utilized for synthesis of a new type of macrocyclic derivatives 186 from the corresponding macrocyclic polyethers 185 which were formed via 183 and 184 (equations 84 and 85). This very rapid reaction results in good yields of potential host molecules and supramolecular building blocks under mild conditions, instead of the thermal treatment. 

It has been reported that subjection of an 11-membered macrocycle involving an alkyne and alkenes to a radical cyclization procedure leads to a tandem cyclization giving rise to the formation of a fused 6,7-bicychc framework [249]. It should be mentioned that the in situ methodology for generation of organotin hydride works... 

Lagana, A. et al., Sample preparation for determination of macrocyclic lactone myco-toxins in fish tissue, based on on-line matrix solid-phase dispersion and solid-phase extraction cleanup followed by liquid chromatography/tandem mass spectrometry, J. AOACInt., 86(4), 729, 2003. 

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