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A synthesis of unconjugated (E)‐enediynes from allenyl amino alcohols is reported and their gold‐catalyzed cascade cycloaromatization to a broad range of enantioenriched substituted isoindolinones has been developed. Experimental and computational studies support the reaction proceeding via a dual‐gold σ,π‐activation mode, involving a key gold‐vinylidene‐ and allenyl‐gold‐containing intermediate. [ABSTRACT FROM AUTHOR]

A novel strategy for the stereoselective synthesis of conjugated enynes directly from α‐allenols has been developed. The reaction proceeds with perfect E‐selectivity and exhibits high functional group compatibility. This catalytic system can also be applied to the stereoselective synthesis of conjugated dienynes and enediynes. [ABSTRACT FROM AUTHOR]

Tiancimycin (TNM) A, a recently discovered enediyne natural product from Streptomyces sp. CB03234, showed rapid and complete killing of cancer cells and could be used as a payload in antibody drug conjugates. The low yield of TNM A in the wild-type strain promoted us to use ribosome engineering and fermentation optimization for its yield improvement. The Streptomyces sp. CB03234-R-16 mutant strain with a L422P mutation in RpoB, the RNA polymerase β-subunit, was obtained from the rifamycin-resistant screening. After fermentation optimization, the titers of TNM A in Streptomyces sp. CB03234-R-16 reached to 22.5 ± 3.1 mg L−1 in shaking flasks, and 13 ± 1 mg L−1 in 15 L fermentors, which were at least 40-fold higher than that in the wild-type strain (~ 0.3 mg L−1). Quantitative real-time RT-PCR revealed markedly enhanced expression of key genes encoding TNM A biosynthetic enzymes and regulators in Streptomyces sp. CB03234-R-16. Our study should greatly facilitate the future efforts to develop TNM A into a clinical anticancer drug. [ABSTRACT FROM AUTHOR]

Opportunities were outlined for application of available KF as a source of fluoride ions and a base in desilylation/the Sonogashira coupling reactions under conditions of a one-pot process. [ABSTRACT FROM AUTHOR]

Cis-enediyne-type compounds have received much attention as potent antitumor antibiotics. The conventional synthesis of cis-enediynes in solution typically involves multiple steps and various side reactions. For the first time, selective one-step synthesis of cis-enediyne from a single reactant is reported on a Ag(111) surface with a yield up to 90 %. High selectivity for the formation of cis-enediyne originates from the steric effect posed by weak intermolecular interactions, which protect the cis-enediyne from further reaction. A series of comparative experiments and DFT-based transition-state calculations support the findings. The described synthetic approach for directing reaction pathways on-surface may illuminate potential syntheses of other unstable organic compounds. [ABSTRACT FROM AUTHOR]

An efficient iodine-mediated regioselective tandem approach for the synthesis of symmetric and asymmetric iodo-substituted indenes and stereoselective cyclopenta [ b]pyridine/thiophenes from easily accessible enediynes that proceeds by in situ formation of an iodonium intermediate followed by a regioselective 5-endo-dig cyclization has been described. The intramolecular electrophilic iodocyclization was selectively triggered by a distribution of electronic density along the alkyne bond. Subsequently, the iodo-substituted indenes were diversified by employing palladium-catalyzed cross-coupling reactions and the coupled products were further confirmed by X-ray crystallographic studies. [ABSTRACT FROM AUTHOR]

An efficient synthesis of panaxytriol and its seven stereoisomers was achieved, and four unnatural diastereomers of 2a were prepared. The key steps involved the opening of vicinal hydroxy epoxides, the stereospecific opening of the epoxides with perchloric acid, and the Cadiot–Chodkiewicz cross-coupling of chiral terminal alkynes with bromoalkynes. Preliminary antitumor activity investigations indicated that some synthetic panaxytriols exhibited promising cytotoxic activity against three human cancer cell lines. [ABSTRACT FROM AUTHOR]

The first bimolecular oxygenative annulation of enediyne compounds leading to naphthalene frameworks has been developed by using Pd(OAc)2 as the catalyst in the presence of NaI under O2 (1 atm). This reaction provided efficient access to a class of symmetric core-annulated naphthalenes by the homoannulation of enediyne–imides. Intriguingly, the crossover annulation of enediyne–imides and other functionalized enediynes could also be achieved by the same catalytic system, resulting in the formation of several unsymmetrical naphthalene derivatives. Preliminary mechanistic investigation using 18O isotopic labelling and radical scavengers indicated that radical oxygen incorporation cascades might be involved in this conversion. [ABSTRACT FROM AUTHOR]

Covering: 1994–2015 The total syntheses of 33 complex natural O-glycosides, such as the glycosides of macrocyclic lactones/lactams, enediynes, angucyclines, and anthracyclines, are highlighted, with a major focus being placed on the O-glycosylation reactions which connect the saccharides and the aglycones. These successful O-glycosylation reactions employ such donors as glycosyl bromides, fluorides, iodides, trichloroacetimidates, N-phenyl trifluoroacetimidates, thioglycosides, sulfoxides, heteroaryl thioglycosides, 1-hydroxyl sugars, 1-O-acetates, and ortho-alkynylbenzoates. Each synthesis is depicted starting from the O-glycosylation of the aglycone (or its precursor); the glycosylation conditions and outcomes (yields and stereoselectivities) are discussed, and the subsequent transformations toward the final target, including the elongation of the glycan, the elaboration of the aglycone, and the protecting group manipulations are also given in detail. [ABSTRACT FROM AUTHOR]

The feasibility of ring-closing metathesis (RCM) as a synthetic entry to 10- and 11-membered dienediynes fused to a benzothiophene core was explored by experimental and theoretical investigations. An established sequence of iodocyclization of o-(buta-1,3-diynyl)thioanisoles followed by Sonogashira coupling to form diethynylbenzothiophenes was used to synthesize terminal benzothiophene-fused enediyne diolefins as substrates for RCM. Encountering an unexpected lack of reactivity of these substrates under standard RCM conditions, we applied DFT calculations to reveal that the underlying cause was a positive change in Gibbs free energy. The change in Gibbs free energy was also found to be positive for RCM of indole- and benzannulated terminal diolefins when affording smaller than 12-membered rings. We found that modification of the enediyne-diolefin substrate as the Co2(CO)6-alkyne complex allowed the target benzothiophene-fused 11-membered dienediyne to be obtained via RCM; the alkyne complexation strategy therefore provides one valid technique for overcoming challenges to macrocyclization of this kind. [ABSTRACT FROM AUTHOR]

Abstract: CF3-containing diyne, readily prepared from (Z)-2,3,3,3-tetrafluoro-1-iodoprop-1-ene in two steps, was smoothly subjected to carbocupration reaction with various organocuprates, followed by treatment of the resultant carbocupration adducts with iodine, the corresponding vinyl iodides being formed in good yields in a cis-addition manner. Thus obtained iodide could be successfully converted into CF3-substituted trans-enediynes in high yields. Also, hydrostannation reaction of the diyne proceeded well in a trans-addition manner to give the corresponding vinylstannane in high yield. The vinylstannane was also found to be effectively convertible to CF3-substituted cis-enediynes in high yields. [Copyright &y& Elsevier]

Theconvergent synthesis of a class of enediyne-imides as wellas their palladium-catalyzed branching cyclizations, which can beaccomplished in two ways leading to a set of polysubstituted furo[2,3-b]pyridines upon using the N-tosyl carboxamidemoiety as an N,O-bisnucleophile,are presented. [ABSTRACT FROM AUTHOR]

The readily available complex 1,1-dibromo-2-ferrocenylethyleneprovides a convenient entry point for the preparation of a wide rangeof cross-conjugated 1,1-bis(alkynyl)-2-ferrocenylethenes through simplePd(0)/Cu(I)-mediated cross-coupling reactions with 1-alkynes. Theferrocene moiety in compounds of the general form FcCHC(CCR)2is essentially electronically isolated from the cross-conjugatedπ system, as evidenced by IR and UV–vis spectroelectrochemicalexperiments and quantum chemical calculations. In contrast to theother examples which give stable ferrocenium derivatives upon electrochemicaloxidation, the aniline derivatives [FcCHC(CCC6H4NH2-4)2]+and[FcCHC(CCC6H4NMe2-4)2]+proved to be unstable on the time scaleof the spectroelectrochemical experiments, leading to passivationof the electrode surface over time. There is no significant thermodynamicstabilization of the radical anion [FcCHC(CCC6H4NO2-4)2]−relative to the neutral and dianionic analogues, although the dianion[FcCHC(CCC6H4NO2-4)2]2–could be studied as a relatively chemicallystable species and is well described in terms of two linked nitrophenylradicals. The capacity to introduce a relatively isolated point chargeat the periphery of the cross-conjugated π system appears tomake these complexes useful templates for the construction of electrochemicallygated quantum interference transistors. [ABSTRACT FROM AUTHOR]

Despite considerable interest in the enediyne family of antitumor antibiotics, assembly of their polyketide core structures in nature remains poorly understood. Discriminating methods to access enzyme-bound intermediates are critical for elucidating unresolved polyketide and nonribosomal peptide biosynthetic pathways. Here, we describe the development of broadly applicable techniques for the mild chemical release and analysis of intermediates bound to carrier proteins (CPs), providing access to these species even in sensitive systems. These techniques were applied to CalE8, the polyketide synthase (PKS) involved in calicheamicin biosynthesis, facilitating the unambiguous identification of enzyme-bound polyketides on an enediyne PKS. Moreover, these methods enabled the preparation of fully unloaded CalE8, providing a "clean slate" for reconstituted activity and allowing us to demonstrate the preferential accumulation of a PKS-bound octaketide with evidence of programmed processing control by CalE8. This intermediate, which has the expected chain length for enediyne core construction, could previously only be indirectly inferred. These studies prove that this polyketide is an authentic product of CalE8 and may be a key precursor to the enediyne core of calicheamicin, as it is the only programmed, enzyme-bound species observed for any enediyne system to date. Our experimental advances into a generally inaccessible system illustrate the utility of these techniques for investigating CP-based biosynthetic pathways. [ABSTRACT FROM AUTHOR]

A novel group of symmetrical and asymmetrical acyclic enediynes has been synthesized by using Sonogashira coupling conditions and characterized spectroscopically. Supplemental materials are available for this article. Go to the publisher's online edition ofSynthetic Communications® to view the free supplemental file. [ABSTRACT FROM AUTHOR]

Biosynthesis of the enediyne natural product dynemicin in Micromonospora chersina is initiated by DynE8, a highly reducing iterative type I polyketide synthase that assembles polyketide intermediates from the acetate units derived solely from malonyl-CoA. To understand the substrate specificity and the evolutionary relationship between the acyltransferase (AT) domains of DynE8, fatty acid synthase, and modular polyketide synthases, we overexpressed a 44-kDa fragment of DynE8 (hereafter named ATDYN10) encompassing its entire AT domain and the adjacent linker domain. The crystal structure at 1.4 Å resolution unveils a α/β hydrolase and a ferredoxin-like subdomain with the Ser-His catalytic dyad located in the cleft between the two subdomains. The linker domain also adopts a α/β fold abutting the AT catalytic domain. Co-crystallization with malonyl- CoA yielded a malonyl-enzyme covalent complex that most likely represents the acyl-enzyme intermediate. The structure explains the preference for malonyl-CoA with a conserved arginine orienting the carboxylate group of malonate and several nonpolar residues that preclude α-alkyl malonyl-CoA binding. Co-crystallization with acetyl-CoA revealed two noncovalently bound acetates generated by the enzymatic hydrolysis of acetyl- CoA that acts as an inhibitor for DynE8. This suggests that the AT domain can upload the acyl groups from either malonyl- CoA or acetyl-CoA onto the catalytic Ser651 residue. However, although the malonyl group can be transferred to the acyl carrier protein domain, transfer of the acetyl group to the acyl carrier protein domain is suppressed. Local structural differences may account for the different stability of the acyl-enzyme intermediates. [ABSTRACT FROM AUTHOR]

A novel group of asymmetrical and symmetrical acyclic enediyne-triazole conjugates have been synthesized by using Sonogashira coupling and Click chemistry. [ABSTRACT FROM AUTHOR]

The intramolecular nitrile oxide-alkene cycloaddition has been studied in an enediyne system. It has been shown to be an efficient method for one-step synthesis of isoxazoline-fused bicyclic enediynes. The thermal reactivity of these enediynes is similar to the isoxazolidine-fused counterparts, thus ruling out any significant effect by the bridgehead double bond. [ABSTRACT FROM AUTHOR]

Electrophilic cyclization of diynylbenzoates (I) followed by Sonogashira coupling of the resulting 4-iodoisocoumarins with acetylenes affords the title products (IV). [ABSTRACT FROM AUTHOR]

A novel group of O-, N-, and S-substituted symmetrical and asymmetrical acyclic enediynes are obtained under Sonogashira coupling conditions. [ABSTRACT FROM AUTHOR]