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The combined organic extracts were washed with 10% aqueous Na SB 2 sb S SB 2 sb O SB 2 sb , water, brine, dried over Na SB 2 sb SO SB 4 sb , and concentrated to give the crude product. After stirring for 2 h, the reaction mixture was cooled to 0 °C and auxiliary B 22 b (4.8 g, 20.8 mmol) in CH SB 2 sb Cl SB 2 sb (10 mL) was added dropwise, followed by DIPEA (4 mL, 22.4 mmol) after 5 min. Reactions were monitored by thin-layer chromatography (TLC) carried out on 0.25 mm silica gel glass plates (60-F254) that were analyzed by fluorescence upon 254 nm irradiation or by staining with I p i -anisaldehyde/AcOH/H SB 2 sb SO SB 4 sb /EtOH, (NH SB 4 sb ) SB 6 sb Mo SB 7 sb O SB 24 sb -4H SB 2 sb O/H SB 2 sb SO SB 4 sb . Keywords: macrodiolides; tartrolons; C3-C22 fragment; 1,5-asymmetric aldol; Sonogashira coupling EN macrodiolides tartrolons C3-C22 fragment 1,5-asymmetric aldol Sonogashira coupling 2134 2142 9 07/03/23 20230718 NES 230718 A class of 42-membered I C i SB 2 sb -symmetric polyketide macrodiolides known as tartrolons have been discovered in a wide range of microbial species. [Extracted from the article]

Macrolactones constitute a privileged class of natural and synthetic products with a broad range of applications in the fine chemicals and pharmaceutical industry. Despite all the progress made towards their synthesis, notably from seco‐acids, a macrolactonization promoter system that is effective, selective, flexible, readily available, and, insofar as possible, compatible with manifold functional groups is still lacking. Herein, we describe a strategy that relies on the formation of a mixed anhydride incorporating a pentafluorophenyl group which, due to its high electronic activation enables a convenient access to macrolactones, macrodiolides and esters with a broad versatility. Kinetic studies and DFT computations were performed to rationalize the reactivity of the pentafluorophenyl group in macrolactonization reactions. [ABSTRACT FROM AUTHOR]

Efficient methods have been developed for synthesizing previously unknown macrodiolides incorporating 1Z,5Z-diene and 1,3-diyne moieties in 54–84% yields and with >98% stereoselectivity by means of the intermolecular cyclocondesation of (7Z,11Z)-octadeca-7,11-dienedioic acid with α,ω-diols catalyzed by hafnium triflate Hf(OTf)4 as well as via the oxidative coupling of α,ω-diynes obtained by the esterification of (7Z,11Z)-octadeca-7,11-dienedioic acid with alkynols. The synthesized macrodiolides exhibit cytotoxic activity toward the Jurkat, K562, U937, HL-60, HeLa, and Hek293 cell lines in vitro.

The synthesis of previously undescribed aromatic polyether macrodiolides containing a 1Z,5Z-diene moiety was carried out in 56–72% yields and with >98% stereoselectivity. It has been shown that the synthesized macrodiolides exhibit higher cytotoxic activity in vitro against a number of tumor cell lines (Jurkat, K562 and U937).

An original strategy has been developed for the synthesis of valuable unsaturated macrocyclic lactones, macrodiolides, containing a 1Z,5Z-diene moiety in 57–79% yields and >98% stereoselectivity by hafnium triflate Hf(OTf) 4 -catalyzed intermolecular esterification of aliphatic α,ω-dicarboxylic acids with α,ω-alka-nZ,(n+4)Z-dienediols (1,12-dodeca-4Z,8Z-dienediol, 1,14-tetradeca-5Z,9Z-dienediol, 1,18-octadeca-7Z,11Z-dienediol). The diols were obtained by homo-cyclomagnesiation of tetrahydropyran ethers of oxygenated 1,2-dienes with EtMgBr in the presence of Mg metal and Cp 2 TiCl 2 catalyst (10 mol. %). The resulting macrodiolides exhibit high cytotoxic activity in vitro against Jurkat, K562, U937, Hek293 and HeLa tumor cell lines. [ABSTRACT FROM AUTHOR]

Talarodiolide, a new 12-membered macrodiolide, was isolated and characterized from the culture filtrate of strain LT6 of Talaromyces pinophilus. The structure of (Z)-4,10-dimethyl-1,7-dioxa-cyclododeca-3,9-diene-2,8-dione was assigned essentially based on NMR and MS data. Furthermore, several known compounds were isolated and identified in the crude extract of the culture filtrate and mycelium of this strain. EI mass spectrum at 70 eV of all isolated metabolites was acquired and compiled in a custom GC/MS library to be employed to detect metabolites in the crude extracts.

A stereodivergent approach to creation of a specific 14-membered macrolide library is described. We designed a new 14-membered macrolide template possessing 10 sterogenic centers, and established a new library of fully-synthesized 14-membered ring compounds. The designed macrodiolides were synthesized through a convergent approach using an Evans aldol reaction, Keck esterification, and Yamaguchi macrolactonization, or Mitsunobu macrolactonization, as key steps. Moreover, introduction of an aminosugar to a macrodiolide aglycone by Schmidt glycosylation also afforded a new macrodiolide. Comparison between the conformation analysis of the macrolides, which we designed, and NMR analysis of the synthetic macrolides, indicated our stereoisomer library has significant diversity. [ABSTRACT FROM AUTHOR]

The asymmetric total synthesis of (+)-marinomycin A, a 44-membered macrodiolide antitumor agent and antibiotic isolated from a marine actinomycete, Marinispora strain CNQ-140, is reported. The key features of the synthesis include the highly convergent stereocontrolled construction of the monomeric hydroxy salicylate starting from asymmetric epoxidation of the σ-symmetrical dialkenyl carbinol, and an unprecedented direct dimerization through NaHMDS-promoted double transesterification. [ABSTRACT FROM AUTHOR]

Abstract: Tandem reaction of α-diazocarbonyl compounds in the presence of rhodium(II) acetate catalyst is described to furnish a range of conformationally restricted C2 symmetric macrodiolides via head to tail dimerization of intramolecular carbonyl ylides. [Copyright &y& Elsevier]

Abstract: Chiral lactones were synthesized from d-mannitol. C 2-symmetric triene precursors were constructed with a central relay-olefin allowing the key domino ring-closing metathesis to be achieved. It led to the symmetrical cleavage of the substrate and to the formation of 2 mol of the desired 5- or 6-membered lactone. Attempts to form 7-membered lactones thus far only led to 14-membered macrodiolides instead. [Copyright &y& Elsevier]

Abstract: The response of Avena sterilis to the phytotoxic fungal metabolite (8R,16R)-(−)-pyrenophorin was studied under illumination. The phytotoxicity of pyrenophorin at 70μM was expressed as bleaching of leaf sections which was accompanied by increased electrolyte leakage, elevated superoxide dismutase activity, severe lipid peroxidation, rapid loss of photosynthetic pigments, and a decline in total protein. Proteolytic enzyme activity in the treated tissues was not affected and remained at the same low levels as in the untreated. Pyrenophorin exerts its phytotoxicity through a mechanism operating under both light and dark as indicated by electrolyte leakage measurements. The presence of PSII inhibitor diuron (172μM) did not reverse electrolyte leakage and bleaching caused by pyrenophorin. The results indicate that the oxidative damage triggered in A. sterilis by the phytotoxin is not light dependent and is exerted through a mechanism which involves electron misdirection and generation of reactive oxygen species. [Copyright &y& Elsevier]

The synthesis of a masked northern half of the natural product disorazole D1 and a cyclopropane analog of the masked northern half of disorazole A1 is described. The synthesis involves in both cases as key steps a Z-selective Wittig olefination and a Sonogashira cross-coupling reaction. [Copyright &y& Elsevier]

• Catalytic synthesis of new 1Z,5Z-diene macrodiolides have been developed. • New molecules are efficient apoptosis inducers in cancer cells. • Macrodiolides suppress phosphorylation of Akt and p38 kinases and CREB transcription factor. • The structures of all novel compounds were confirmed by NMR measurements. An original scheme was developed for the synthesis of previously undescribed unsaturated macrodiolides containing a 1Z,5Z-diene moiety in 44–80% yields and with high stereoselectivity (>95%) based on the intermolecular esterification of α,ω-diols with α,ω-alka-nZ,(n + 4)Z-dienedicarboxylic acids (1,12-dodeca-4Z,8Z-dienedicarboxylic acid, 1,14-tetradeca-5Z,9Z-dienedicarboxylic acid, 1,18-octadeca-7Z,11Z-dienedicarboxylic acid) catalyzed by hafnium triflate [Hf(OTf) 4. The unsaturated dicarboxylic acids were prepared via homo-cyclomagnesiation of tetrahydropyran ethers of O-containing 1,2-dienes with EtMgBr in the presence of Mg metal and the Cp 2 TiCl 2 catalyst (10 mol.%) and the subsequent Jones oxidation of pyran ethers formed after the acid hydrolysis of magnesacyclopentanes. The thus prepared macrodiolides exhibit high cytotoxic activity in vitro against Jurkat, K562, U937, Hek293 and HeLa cancer cell lines. It was found that induction of the programmed cell death in Jurkat cells by macrodiolides corresponds to the mitochondrial apoptosis pathway. Also, it was shown that the prepared macrodiolides efficiently suppress phosphorylation of Akt and p38 kinases and CREB transcription factor in cancer cells. [ABSTRACT FROM AUTHOR]

Talarodiolide, a new 12-membered macrodiolide, was isolated and characterized from the culture filtrate of strain LT6 of Talaromyces pinophilus. The structure of (Z)-4,10-dimethyl-1,7-dioxa-cyclododeca-3,9-diene-2,8-dione was assigned essentially based on NMR and MS data. Furthermore, several known compounds were isolated and identified in the crude extract of the culture filtrate and mycelium of this strain. EI mass spectrum at 70 eV of all isolated metabolites was acquired and compiled in a custom GC/MS library to be employed to detect metabolites in the crude extracts. [ABSTRACT FROM AUTHOR]