Long-term depression (LTD) induced by low-frequency synaptic stimulation (LFS) was originally introduced as a model to probe potential mechanisms of deprivation-induced synaptic depression in visual cortex. In hippocampus, LTD requires activation of postsynaptic NMDA receptors, PKA, and the clathrin-dependent endocytosis of ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. It has long been assumed that LTD induced in visual cortical layer 2/3 by LFS of layer 4 uses similar mechanisms. Here we show in mouse visual cortex that this conclusion requires revision. We find that LTD induced in layer 2/3 by LFS is unaffected by inhibitors of PKA or ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor endocytosis but is reliably blocked by an endocannabinoid CB1 receptor antagonist. Conversely, LFS applied to synapses on layer 4 neurons produces LTD that appears mechanistically identical to that in CA1 and is insensitive to CB1 blockers. Occlusion experiments suggest that both mechanisms contribute to the loss of visual responsiveness after monocular deprivation.endocannabinoid ͉ glutamate receptor ͉ long-term depression ͉ ocular dominance plasticity

Dedicated to Professor Kendall N. Houk on the occasion of his 70th birthday Furan derivatives are widely found in natural products with impressive biological properties. In many of these natural products, the furan system is fused to other rings with various sizes. Some of the natural products that incorporate sevenmembered-ring-fused furans are shown in Figure 1. [1] Among these natural products, frondosin B inhibits the binding of interleukin-8 (IL-8) in the low micromolar range. [1a] Liphagal is a selective inhibitor of phosphatidylinositol 3-kinase a (PI3K a). [1b] These days, the synthesis of seven-membered ring systems still represents a great challenge for synthetic organic chemists. [2] Consequently, the development of reactions or the design of strategies to build the fused cycloheptafuran skeleton is, in many cases, a challenging part of the synthesis of natural products with seven-membered-ringfused furans, such as frondosin B, and their analogues. [3] Transition-metal-catalyzed alkenylation reactions of arenes, [4] such as substituted benzenes, [5] indoles, [6] or pyrroles, [7] with alkynes have been rapidly developed over the past decade, owing to the discovery of alkyne activation by electrophilic transition-metal complexes. [8] However, in most cases, transition-metal-catalyzed intramolecular reactions of furans with alkynes give products where the furan ring has opened rather than alkenylated furans. [9][10][11][12][13] The cationic spiro intermediate A (Scheme 1 a) was proposed as a common intermediate of gold-catalyzed a-yne-furan cycloisomerizations. [14] Intermediate A may undergo 1,2-migration to form the annulated intermediate B, which gives the b-alkenylated furan product after proton transfer. However, in most cases, A undergoes CÀO bond cleavage, and further steps occur that lead to a furan-ring-opened product.Considering that the a position of furans is more nucleophilic than the b position, [15] we wondered whether we could develop an a-alkenylation strategy that uses furan substrates with the alkyne chain attached at the b position of the furan ring; then, the annulated furan intermediate C would be formed directly (no 1,2-migration needed), and consequently, fewer side reactions should occur (Scheme 1 a). We found that only five examples of transition-metal-catalyzed a-alkenylation reactions of b-yne-furans have been reported by the groups of Echavarren (Pt), Sames (Pt), Yamamoto (Pd), Nishizawa (Hg), and Banwell (Au). [16] However, only fused cyclohexafurans were formed by an exo-selective Friedel-Crafts type cyclization. We envisioned that there are two possible competing a-alkenylation pathways for b-yne-furans that would give the six-and seven-membered-ring products, respectively. We wondered whether this regioselectivity could be tuned by electronic effects through the introduction of suitable substituents on the alkyne moiety or on the tether of Figure 1. Natural products with seven-membered-ring-fused furans. Scheme 1. a) Different reaction pathways of a-yne-furans and b-ynef...

The presented step‐economic synthesis of complex molecules proceeds with moderate to excellent diastereoselectivity.

Previously reported was that cis-ene-vinylcyclopropanes (cis-ene-VCPs) underwent Rh-catalyzed [5+2] reaction to give 5,7-fused bicyclic products, where vinylcyclopropane (VCP) acts as five-carbon synthon. Unfortunately, this reaction had very limited scope. Replacing the 2π component of cis-ene-VCPs to allene moiety, the corresponding cis-allene-VCPs did not undergo the expected normal [5+2] cycloaddition to give 5,7-fused bicyclic products. Instead, the challenging bicyclo[4.3.1]decane skeleton was obtained via an unprecedented bridged [5+2] cycloaddition. DFT calculations were applied to understand why this bridged [5+2] reaction is favored over the anticipated but not realized normal [5+2] reaction.

Reported herein is the first rhodium-catalyzed [4+2+1] cycloaddition of in situ generated ene/yne-ene-allenes and CO to synthesize challenging seven-membered carbocycles fused with five-membered rings. This reaction is designed based on the 1,3-acyloxy migration of ene/yne-ene-propargyl esters to ene/yne-ene-allenes, followed by oxidative cyclization, CO insertion, and reductive elimination to form the final [4+2+1] cycloadducts. The possible competing [4+1], [4+2], and [2+2+1] cycloadditions were disfavored, making the present reaction an efficient way to access functionalized 5/7 rings.

A Rh-catalysed [5 + 1] cycloaddition of allenylcyclopropanes and CO has been developed to synthesize functionalized 2-methylidene-3,4-cyclohexenones. The scope of this methodology has been investigated, showing that various functional groups can be tolerated. Both di- and tri-substituted allenylcyclopropanes can be applied to this cycloaddition and the [5 + 1] cycloadducts with the E configuration were obtained as the major products. In addition, the present [5 + 1] cycloaddition reaction has been utilized as a key step in the formal synthesis of the natural product (-)-galanthamine.

Alkenylierung von Furanen: Eine effiziente Gold‐katalysierte endo‐selektive intramolekulare α‐Alkenylierung von β‐Alkin‐substituierten Furanen ermöglicht die Synthese von Siebenring‐anelliertem Furan mit guten bis exzellenten Ausbeuten. Dichtefunktionalrechnungen wurden durchgeführt, um ein verbessertes Verständnis der beobachteten Regioselektivität zu gewinnen. DME=1,2‐Dimethoxyethan, Ts=p‐Toluolsulfonyl.

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