Macrocyclic ketolactones

Other interesting synthetic applications of the ketone-derived enamine alkylation are found in the monomethylation of steroid enamines (249), extension of the benzylation reaction (250) to a ferrocene derivative (251), the use of a-bromoesters (252) and ketones (252) or their vinylogues (25J), in the syntheses of alantolactone (254-256), isoalantolactone (257), and with a bridged bis-enamine (258). The use of bifunctional alkylating agents is also seen in the introduction of an acetylenic substituent in the synthesis of the characteristic fragrant constituent of jasmine (259), the synthesis of macrocyclic ketolactones (260), the use of butyrolactone (261), and the intermolecular or intramolecular double alkylations of enamines with dihalides (262). 

Oxidative fission of the pyran ring in 199 (n = 4, 5, 6 or 10) with ra-chloroperbenzoic acid has been used to obtain medium and macrocyclic ketolactones 200 (equation 85)105. 

Thermolysis of dispiro-l,2,4-trioxane 66 affords the macrocyclic ketolactone 67. P-Scission of the cyclohexane ring is accelerated by the a-methoxy in accord with DFT calculations <07OL5569>. 

Macrocyclic ketolactones, synthesis of via desulfurization 88MI17 90MI13. 

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. 

Semisynthesis and degradation of the tubulin inhibitors epothilone (macrocyclic ketolactone) and tubulysin (thiazole derivative) 03PAC167. 

Borowitz has encountered perhaps predictable difficulties in the attempted extension of his synthesis of macrocyclic ketolactones preparation of the requisite enol ethers, simple in the bicyclo[4,4,0) series, presented considerable difficulty in the bicyclo[5,5,0] series. A variant of such an oxidative enol ether cleavage has been reported, where oximinolactones are formed... 

Mahajan has described a novel route to macrocyclic ketolactones using a retro-Dieckmann reaction (Scheme 24). Although perhaps not of general applicability, the method appears attractive for the synthesis of the type of molecule shown in the scheme. The same idea of bond fission of polycyclic systems to form macro-lides has been used to prepare ketolactones from 2,3-polymethylene-benzo- and -naphtho-pyrans by oxidative cleavage (Scheme 25). 

The direct comparison of 1 and 2 in a variety of RCM reactions also indicates a presumably close relationship between these catalysts (Table 1) [6]. Both of them give ready access to cycloalkenes of almost any ring size > 5, including medium sized and macrocyclic products. Only in the case of the 10-membered jasmine ketolactone 16 was the yield obtained with 2a lower than that with lc this result may be due to a somewhat shorter lifetime of the cationic species in solution. However, the examples summarized in Table 1 demonstrate that the allenylidene species 2 exhibit a remarkable compatibility with polar functional groups in the substrates, including ethers, esters, amides, sulfonamides, ketones, acetals, glycosides and even free hydroxyl groups. 

Fast Atom Bombardment-Fourier Transform-Mass Spectrometry (FAB-FT-MS) and low-energy collisional activation experiments proved that the oligomers of j3-ketolactone generally have a macrocyclic ring structure rather than a catenane ring. ... 

Wu, J., Chen, C., Kurth, M.J., and LebrUla, C.B., Mass Spectrometry Analyses of j8-Ketolactone Oligomers, Macrocyclic or Catenane Structures, Anal. Chem., 68, 38, 1996. 

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