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Lewis acid catalyzed ring opening of 1,1-cyclopropanediesters by the hydroxyl group of a propargyl alcohol sets up a subsequent Conia-ene cyclization to produce substituted tetrahydropyrans in a one-pot, high-yielding procedure.

The preparation of the ferrocene-based reagents FcSSiMe3 ( 1) and fc(SSiMe3)2 ( 2) [Fc = (η5-C5H5)Fe(η5-C5H4)-; fc = Fe(η5-C5H4)2-] is reported together with their use in the formation of the tetrahedral zinc complexes [( N, N′-tmeda)Zn(SFc)2] ( 3a) and [( N, N′-tmeda)Zn(S2fc)] ( 4a), respectively (tmeda = tetramethylethylenediamine). The structures of these coordination complexes are compared to the new ferroceneselenolates [( N, N′-tmeda)Zn(SeFc)2] ( 3b) and [( N, N′-tmeda)Zn(Se2fc)] ( 4b), themselves prepared using FcSeSiMe3 and fc(SeSiMe3)2, respectively. The synthesis and characterization of dimeric [Cd2(µ-EFc)2(EFc)2(PPr3)2] ( 5a, E = S; 5b, E = Se) are also described. [ABSTRACT FROM AUTHOR]

The intramolecular reaction of donor-acceptor cyclopropanes with various dipoles and dipolar equivalents allows access to a variety of bicyclic adducts with good stereo control. The linkers can often be cleaved to provide stereodefined products. [ABSTRACT FROM AUTHOR]

Review: 93 refs. [ABSTRACT FROM AUTHOR]

We report the modular preparation of dihydro-1,2,5-thiodiazole dioxide heterocycles starting from methyl ketones and primary amines. This one-pot, three-component coupling employs 2,3-dimethylimidazole-1-sulfonyl azide triflate as a coupling reagent and oxidant. The transformation is scalable and various ketones and amines can be used, yielding thiodiazole dioxide products in up to 89% yield. In addition, 15 N- and 13 C-labeling studies suggest a mechanism involving a 1,2-nitrogen migration. Together with the mechanistic studies, DFT calculations provide insight into the reaction pathway and set the stage for further exploration of the mechanistic nuances of reactions that use sulfamoyl azides. In combination with the demonstrated modularity of the approach reported herein, the derivatization of the thiodiazole dioxide products highlights the potential of this methodology to rapidly access diverse chemical structures., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The secondary metabolites that comprise the diterpenoid alkaloids are categorized into C 18 , C 19 , and C 20 families depending on the number of contiguous carbon atoms that constitute their central framework. Herein, we detail our efforts to prepare these molecules by chemical synthesis, including a photochemical approach, and ultimately a bioinspired strategy that has resulted in the development of a unifying synthesis of one C 18 (weisaconitine D), one C 19 (liljestrandinine), and three C 20 (cochlearenine, paniculamine, and N-ethyl-1α-hydroxy-17-veratroyldictyzine) natural products from a common intermediate.

The denudatine-type diterpenoid alkaloids cochlearenine, N-ethyl-1α-hydroxy-17-veratroyldictyzine, and paniculamine have been synthesized for the first time (25, 26, and 26 steps from 16, respectively). These syntheses take advantage of a common intermediate (8) that we have previously employed in preparing aconitine-type natural products. The syntheses reported herein complete the realization of a unified strategy for the preparation of C20, C19, and C18 diterpenoid alkaloids., Competing Interests: Notes The authors declare no competing financial interest.

Orexins (OXs) are peptides produced by perifornical (PeF) and lateral hypothalamic neurons that exert a prominent role in arousal-related processes, including stress. A critical role for the orexin-1 receptor (OX1R) in complex emotional behavior is emerging, such as overactivation of the OX1R pathway being associated with panic or anxiety states. Here we characterize a brain-penetrant, selective, and high-affinity OX1R antagonist, compound 56 [N-({3-[(3-ethoxy-6-methylpyridin-2-yl)carbonyl]-3-azabicyclo[4.1.0]hept-4-yl}methyl)-5-(trifluoromethyl)pyrimidin-2-amine]. Ex vivo receptor binding studies demonstrated that, after subcutaneous administration, compound 56 crossed the blood-brain barrier and occupied OX1Rs in the rat brain at lower doses than standard OX1R antagonists GSK-1059865 [5-bromo-N-({1-[(3-fluoro-2-methoxyphenyl)carbonyl]-5-methylpiperidin-2-yl}methyl)pyridin-2-amine], SB-334867 [1-(2-methyl-1,3-benzoxazol-6-yl)-3-(1,5-naphthyridin-4-yl)urea], and SB-408124 [1-(6,8-difluoro-2-methylquinolin-4-yl)-3-[4-(dimethylamino)phenyl]urea]. Although compound 56 did not alter spontaneous sleep in rats and in wild-type mice, its administration in orexin-2 receptor knockout mice selectively promoted rapid eye movement sleep, demonstrating target engagement and specific OX1R blockade. In a rat model of psychological stress induced by cage exchange, the OX1R antagonist prevented the prolongation of sleep onset without affecting sleep duration. In a rat model of panic vulnerability (involving disinhibition of the PeF OX region) to threatening internal state changes (i.e., intravenous sodium lactate infusion), compound 56 attenuated sodium lactate-induced panic-like behaviors and cardiovascular responses without altering baseline locomotor or autonomic activity. In conclusion, OX1R antagonism represents a novel therapeutic strategy for the treatment of various psychiatric disorders associated with stress or hyperarousal states., (Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.)

An efficient synthesis of the octahydro-1H-2,4-methanoindene core of phragmalin-type limonoids, such as xyloccensins O and P, is reported. The success of the synthetic route is predicated on the use of network analysis in the retrosynthetic analysis and a Diels-Alder reaction for the synthesis of a key hydrindanone derivative., (© 2012 American Chemical Society)

A Zn(NTf(2))(2) catalyzed tandem reaction consisting of a nucelophilic ring opening of 1,1-cyclopropanediesters by 2-alkynyl indoles followed by a Conia-ene ring closure results in the efficient one-step synthesis of tetrahydrocarbazoles. The adducts may be further elaborated to carbazoles.

The reaction of hydrazinoethyl 1,1-cyclopropanediesters with aldehydes in the presence of catalytic Yb(OTf)(3) allows access to structurally complex fused bicyclo pyrazolidines. Either 2,5-cis or 2,5-trans adducts can be obtained in good to excellent yields in most cases by simply controlling the order of addition of the catalyst and aldehyde.

The reaction of benzyl-protected propargyl amines and 1,1-cyclopropane diesters in the presence of catalytic Zn(NTf(2))(2) allows access to highly functionalized piperidines in excellent yields. The process proceeds via a tandem cyclopropane ring-opening/Conia-ene cyclization.

The first total syntheses of clausamines A-C and clausevatine D are reported. The key step involves a Diels-Alder reaction between an imine quinone and cyclic diene, allowing for the subsequent construction of the carbazole core in a regiospecific manner. Stereochemistry of the natural products is also discussed.

The Diels-Alder reaction between a quinone monoimine and cyclic diene allows for the construction of substituted carbazoles in a regiospecific manner. This methodology has sucessfully been employed in a divergent strategy, culminating in the synthesis of eustifolines A-D and glycomaurrol.

Trimethylsilylselenoferrocene 1 has been prepared in good yield. The reactive silyl group on 1 is used as a driving force for the synthesis [Cl4Cd4[mu2-Se(C5H4)Fe(C5H5))6]2- 2, a Cd4Se6 adamantoid cluster with six surface ferrocenyl groups.