A Rapid Esterification by Means of Mixed Anhydride and Its Application to Large-ring Lactonization

Inanaga, Junji; Hirata, Kuniko; Saeki, Hiroko; Katsuki, Tsutomu; Yamaguchi, Masaru

doi:10.1246/bcsj.52.1989

Cited by 2,187 publications

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“…In the endgame of the synthesis (Scheme 3), the carboxylic acid 2 was first esterified with alcohol 3 according to the Yamaguchi protocol (Inanaga, 1979) to provide the substrate for the macrolactone ring closure. The pivotal intramolecular Heck reaction proceeded smoothly and provided the desired 32-E diene 24 with a better than 20:1 ratio of geometrical isomers, whereas intermolecular coupling gave a mixture of Z and E products.…”

Section: This Is a Pre-or Post-print Of An Article Published Inmentioning

confidence: 99%

Total synthesis of antibiotics: recent achievements, limitations, and perspectives

Prusov

2013

Appl Microbiol Biotechnol

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Section: This Is a Pre-or Post-print Of An Article Published Inmentioning

confidence: 99%

Total synthesis of antibiotics: recent achievements, limitations, and perspectives

Prusov

2013

Appl Microbiol Biotechnol

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“…Now that the key intermediate was obtained enantioselectively, we tried several conditions for asymmetric reduction of the enone 4, and the best selectivity ( / = 9:1 or 1:9) was obtained with the (S)-or (R)-CBS-reagent 11,12) and borane-THF complex. After confirmation of the stereochemistry of each isomer by the modified Mosher's method, 13) hydrolysis was followed by Yamaguchi lactonization 14) to give 10-membered lactone 5 and 6 in satisfactory yield, together with a small amount of a dimeric lactone (5-10%). On the other hand, the CoreyMukaiyama method 15) was found to give only several unidentifiable compounds.…”

Section: Our First Synthesis Of Mueggelonementioning

confidence: 99%

“…Terminal olefin was introduced by a reductive epoxide opening in the presence of zinc 18) to afford 13, which was converted to the corresponding hydroxy acid 14. Yamaguchi lactonization 14) of hydroxy acid 14 gave lactone 15. Olefin cross metathesis 4,19) between precursors 10 and 15 in the presence of the 2nd-generation Grubbs catalyst 20) gave mueggelone with complete E selectivity, but the yield was not very high (40%) because undesired homodimer was generated.…”

Section: Our First Synthesis Of Mueggelonementioning

confidence: 99%

“…The other fragment 37, involving the residual stereocenters, was prepared by Evans aldol reaction 43) using 1,4-butanediol as the starting material. Connection of two fragments 35 and 37 was carried out under the Yamaguchi conditions, 14) and the resulting ester 38 was subjected to RCM using 1st-generation Grubbs catalyst. 26) High dilution conditions (1.4 mM) brought a result similar to Marco's group, 22,23) giving a 2:1 E/Z mixture of 10-membered lactone 39 in good yield.…”

Section: Other Syntheses Of Microcarpalide Employing Rcmmentioning

confidence: 99%

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Synthetic Studies of Natural 10-Membered Lactones, Mueggelone, Microcarpalide, and Sch 642305, Which Have Interesting Bioactivities

Ishigami

2009

Bioscience, Biotechnology, and Biochemistry

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A number of 10-membered lactones have been isolated as secondary metabolites, and many of them have interesting and potent activities. Because of synthetic and biological interests, many synthetic studies of these compounds have been made. This review summarizes synthetic approaches to three natural 10-membered lactones, mueggelone, microcarpalide, and Sch 642305. Mueggelone is an inhibitor of fish development, microcarpalide is a microfilament disrupting agent, and Sch 642305 is an inhibitor of bacterial DNA primase.

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“…Efficient ester formation occurred only under highly optimized reaction conditions, which entailed reaction of 5 with 2,4,6-trichlorobenzoyl chloride 25 at −78°C (to form the mixed anhydride), subsequent simultaneous addition of alcohol 6 and 4-dimethylaminopyridine (DMAP) in toluene, and slow warming of the reaction mixture to −35°C. Using this procedure, the desired ester 19 could be obtained in yields of up to 50% (Scheme 4) (64% for epi-19).…”

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Synthesis and Antimycobacterial Activity of 2,1′-Dihydropyridomycins

Horlacher

Hartkoorn

Cole

et al. 2012

ACS Med. Chem. Lett.

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Dihydropyridomycins 2 and 3, which lack the characteristic enol ester moiety of the potent antimycobacterial natural product pyridomycin (1), have been prepared from L-Thr, R-and S-hydroxy isovaleric acid, and 3-pyridinecarboxaldehyde. The 2R isomer 2 shows only 4-fold lower anti-Mtb activity than 1, indicating that the enol ester moiety in the natural product is not critical for its biological activity. This finding establishes 2 as a potent and more practical lead for anti-TB drug discovery.KEYWORDS: natural products, InhA, pyridomycin, total synthesis, tuberculosis T uberculosis (TB) is a frequently fatal infectious disease that causes more than 1.4 million deaths annually. TB was considered to be well contained in the 1960s, but recent decades have witnessed a resurgence of the disease, even in industrialized countries, due to comorbidity with AIDS and the emergence of multi-and extensively drug-resistant (MDR, XDR) strains of the causative pathogen Mycobacterium tuberculosis (Mtb). 1 These developments were paralleled by a decline in TB-directed drug discovery efforts; thus, as of today, the last TB drug with a novel mode of action was launched more than 40 years ago, and current combination therapy is insufficient to eliminate XDR Mtb. 2 As a consequence, there is an urgent need for the development of new anti-TB agents that can shorten the duration of treatment (current standard first line therapy of TB extends over 6 months) and/or are active against MDR and XDR bacteria.Pyridomycin (1) (Chart 1) is a bacterial natural product that was first isolated from the Streptomyces strain 6706 in 1953. 3,4 The compound was subsequently shown to exhibit significant in vitro antimycobacterial activity and low systemic toxicity in mice. 5 While these findings were not further explored for decades to come, we have recently confirmed the in vitro antimycobacterial activity of 1, which we found to inhibit Mtb growth with a minimal inhibitory concentration (MIC) of 0.3 μg/mL. 6 Moreover, we have identified the molecular target of 1 as the mycobacterial NADH-dependent enoyl-[acyl-carrierprotein] reductase (InhA), 6 which is also the target of the clinical TB drug isoniazid (INH) (after metabolic activation and formation of a NADH adduct as the effective inhibitory species). 7,8 Pyridomycin (1) is a competitive inhibitor at the NADH-binding site of InhA but has not shown cross-resistance with INH. 6 This suggests that the exact molecular interactions of 1 with the NADH-binding site differ from those of the NADH adduct of INH. Together with the fact that the structure of 1 does not resemble any known TB drug, these findings render pyridomycin an auspicious starting point for TB drug discovery.Only a single total synthesis of 1 has been reported in the literature; significant difficulties were encountered in that work 9 with regard to the establishment of the enol ester double bond between C2 and C1′, 10 a problem that could not be solved in a fully satisfactory manner. In light of these difficulties, we felt th...

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A Rapid Esterification by Means of Mixed Anhydride and Its Application to Large-ring Lactonization

Abstract: A rapid and mild esterification method using carboxylic 2,4,6-trichlorobenzoic anhydrides in the presence of 4-dimethylaminopyridine was developed. The method was also successfully applied to the synthesis of large-ring lactones, including Dl-2,4,6-tridemethyl-3-deoxymethynolide.

Cited by 2,187 publications

References 19 publications

Total synthesis of antibiotics: recent achievements, limitations, and perspectives

Total synthesis of antibiotics: recent achievements, limitations, and perspectives

Synthetic Studies of Natural 10-Membered Lactones, Mueggelone, Microcarpalide, and Sch 642305, Which Have Interesting Bioactivities

Synthesis and Antimycobacterial Activity of 2,1′-Dihydropyridomycins

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