Total synthesis of the antifungal dilactones UK-2A and UK-3A: The determination of their relative and absolute configurations, analog synthesis and antifungal activities

Shimano, Masanao; Kamei, Nozomu; Shibata, T.; Inoguchi, Kiyoshi; Itoh, Nobuko; Ikari, Takashi; Senda, Hisato

doi:10.1016/s0040-4020(98)00777-7

Cited by 28 publications

(17 citation statements)

References 34 publications

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“…The starting materials 1a and 1b for 7-butyl-and 7-hexyl-AAs, respectively, were easily prepared by condensation of the corresponding auxiliary and acyl chlorides. [14] First, although the aldol reaction of 1a with aldehyde 3 [15] was tested under exactly the same conditions as in the literature, [14] no aldol adduct was obtained at all and only polymerization of 3 was presumed (Table 1, entry 1).…”

Section: Resultsmentioning

confidence: 99%

Total Synthesis of the (+)‐Antimycin A Family

et al. 2011

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Section: Resultsmentioning

confidence: 99%

Total Synthesis of the (+)‐Antimycin A Family

et al. 2011

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“…The preparation of the title compounds was achieved using one of two general strategies. Alcohol 1 was accessed via the method by Shimano and co‐workers . Using general acylation strategies described in US Patent 6 355 660 B1, acylated Boc‐protected bislactones 2 were prepared in a straightforward manner (Scheme ).…”

Section: Methodsmentioning

confidence: 99%

“…Alcohol 1 was accessed via the method by Shimano and co-workers. [22][23][24] Using general acylation strategies described in US Patent 6 355 660 B1, 25 acylated Boc-protected bislactones 2 were prepared in a straightforward manner (Scheme 1). The cyclopentane ether 3 was accessed via hydrogenation of the vinyl ether resulting from condensation of 1 with cyclopentanone dimethyl acetal (see Supplementary Information).…”

Section: Synthesis Of Title Compounds 5-18 and 33mentioning

confidence: 99%

Synthesis and biological activity of analogs of the antifungal antibiotic UK‐2A. III. Impact of modifications to the macrocycle isobutyryl ester position

Owen

Meyer

Slanec

et al. 2019

Pest Management Science

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BACKGROUND Fenpicoxamid (Inatreq™ active), a new fungicide under development by Corteva Agriscience™, Agriculture Division of DowDuPont, is an isobutyryl acetal derivative of the antifungal antibiotic UK‐2A. SAR studies around the picolinamide ring and benzyl substituents attached at positions 3 and 8, respectively, of the UK‐2A bislactone macrocycle have recently been documented. This study focuses on replacement of the isobutyryl ester group in the 7 position. RESULTS Thirty analogs, predominantly esters and ethers, were prepared and evaluated for inhibition of mitochondrial electron transport and in vitro growth of Zymoseptoria tritici, Leptosphaeria nodorum, Pyricularia oryzae and Ustilago maydis. Aliphatic substituents containing four to six carbon atoms deliver strong intrinsic activity, the pivaloate ester (IC50 1.44 nM) and the n‐butyl, 1‐Me‐propyl, 3,3‐diMe‐propyl and 2‐c‐propyl propyl ethers (IC50 values = 1.08, 1.14, 1.15 & 1.32 nM, respectively) being the most active derivatives. QSAR modelling identified solvation energy (Esolv) and critical packing parameters (vsurf_CP) as highly significant molecular descriptors for explaining relative intrinsic activity of analogs. Activity translation to fungal growth inhibition and disease control testing was significantly influenced by intrinsic activity and physical properties, the cyclopropanecarboxylate ester (log D 3.67, IC50 3.36 nM, Z. tritici EC50 12 μg L−1) showing the strongest Z. tritici activity in protectant tests. CONCLUSIONS Substitution of the isobutyryl ester group of UK‐2A generates analogs that retain strong antifungal activity against Z. tritici and other fungi. © 2019 Society of Chemical Industry

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“…517‐02 . Complete synthesis of UK‐2A was described in 1998 . This fermentation product was used as a precursor for O ‐alkylation of its 3‐hydroxy‐4‐methoxy‐pyrid‐2‐yl moiety and preparation of fenpicoxamid, a new chiral and semi ‐ synthetic picolinamide fungicide controlling major fungal pathogens in wheat and bananas.…”

Section: Fungicidesmentioning

confidence: 99%

Current status of chirality in agrochemicals

Jeschke

2018

Pest Management Science

152

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The agrochemical industry is searching continuously for new pesticides to develop products that have optimal efficacy, lower application rates in the field, increased selectivity, favourable toxicological and environmental safety, enhanced user friendliness and better economic viability. One strategy by which to achieve these ambitious goals makes use of the unique properties of molecules containing asymmetric centres. In the past, many natural products and their congeners have been a source of inspiration in the design of new active ingredients, and the molecular structures of the resulting compounds have become increasingly complex; some 30% contain fragments with asymmetric centres. However, despite enormous progress in catalytic asymmetric processes over the past decade, few agrochemicals are produced in an enantiomerically pure or enriched form on an industrial scale. Since 2007, ∼ 43% of the 44 products launched (insecticides, acaricides, fungicides, nematicides and herbicides) contain one or more asymmetric centres in the molecule (∼ 47%) and most have been launched as racemic mixtures of enantiomers or diastereomers. This review provides an overview of the current status of chiral agrochemicals launched over the past 10 years and describes the inherently connected challenges of modern agricultural chemistry by managing important aspects resulting from the stereochemistry of these innovative products. © 2018 Society of Chemical Industry.

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Total synthesis of the antifungal dilactones UK-2A and UK-3A: The determination of their relative and absolute configurations, analog synthesis and antifungal activities

Cited by 28 publications

References 34 publications

Total Synthesis of the (+)‐Antimycin A Family

Total Synthesis of the (+)‐Antimycin A Family

Synthesis and biological activity of analogs of the antifungal antibiotic UK‐2A. III. Impact of modifications to the macrocycle isobutyryl ester position

Current status of chirality in agrochemicals

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