Total synthesis and biological evaluation of Koshidacin B, TAN-1746, and Ac-TAN-1746.

Analogues of chlamydocin derivatives consistently demonstrate multifaceted bioactivities, particularly through HDAC inhibition mechanisms, oncolytic efficacy, and neuronal preservation capacities. These activities primarily originate from their unique cyclic tetrapeptide scaffold and functional groups within the side chains that enable specific interactions with biomacromolecules. We herein report the total syntheses of three naturally occurring chlamydocin analogues-koshidacin B, TAN-1746, and Ac-TAN-1746.

Biomimetic Synthesis of Myrtucommulones D-E.

A concise and efficient biomimetic synthesis of myrtucommulones D-E has been achieved, proceeding in just 6-7 linear steps from readily available biogenetic building blocks. The key feature of the synthesis was the Zn-mediated skeletal rearrangement reaction, without the need for rare metal photocatalysts and visible light. Based on this biomimetic synthesis, four compounds demonstrated moderate to excellent cytotoxic activities against osteosarcoma cells (U2OS and 143B).

Discovery and Biomimetic Syntheses of Phloroglucinol-Monoterpene-Triketone Hybrids from with Hypoglycemic Activity.

Four pairs of enantiomeric phloroglucinol-monoterpene-triketone hybrids, (+)- and (-)-chameuncinones A-D [(+)- and (-)--], were isolated from the aerial parts of using a building block-based molecular network (BBMN) approach. The planar structures of - were elucidated through comprehensive spectroscopic analyses. A putative biosynthetic pathway for - involving two Diels-Alder reactions was proposed.

Xanthochrysanthones A-C, Novel Lobster-Shape Cinnamoyltriketone Dimers with Antiviral Activities from Xanthostemon chrysanthus.

Three pairs of enantiomeric cinnamoyltriketone dimers, (+)- and (-)-xanthochrysanthones A-C [(+)- and (-)-1-3)], were recognized and obtained from Xanthostemon chrysanthus by employing the building blocks-based molecular network (BBMN) strategy. Compounds 1-3 featured two new types of lobster-shape carbon skeletons with unprecedented spiro[cyclohexane-1,2'-xanthene] or benzo[7,8]oxocino[4,5-b]chromene tetracyclic ring systems. Their structures with absolute configurations were established by comprehensive spectroscopic analyses, X-ray crystallography, and ECD calculations.

Total Synthesis of the Marine Cyclic Depsipeptide Lagunamide D.

Lagunamide D is a structurally distinct 26-membered cytotoxic cyclic depsipeptide, originally isolated from a marine cyanobacterium. It exhibits potent antiproliferative activity in the low nanomolar range against A549 human lung adenocarcinoma cells and HCT116 colon cancer cells. A significant challenge associated with lagunamide D is its propensity for intramolecular acyl migration, which leads to the formation of a contracted 24-membered analog, lagunamide D'.

Garcioblons A-F, Polycyclic Polyprenylated Acylphloroglucinols with Diverse Rearranged Skeletons from .

Garcioblons A-F (-), six unprecedented polycyclic polyprenylated acylphloroglucinols (PPAPs) formed via intramolecular Diels-Alder (IMDA) reactions from monocyclic polyprenylated acylphloroglucinols (MPAPs), were isolated from . Their structures were elucidated through spectroscopic analysis and quantum calculations. Structurally, compound is the first PPAP characterized by an unprecedented 6/6/5/7/6/5/6/5 octacyclic ring system with a 11-oxatetracyclo[8.

Visible-Light Photocatalyzed Skeletal Rearrangement Enables the Synthesis of Highly Functionalized Xanthenes with Antitumor Activity.

Highly functionalized xanthenes possess an impressive range of bioactivities and daunting synthetic challenge due to their unique ring systems and stereocenters. Here, we report an unprecedented ketyl radicals-induced skeletal rearrangement reaction of spirodihydrobenzofurans, enabled by zero-valent iron as reducing agents via photoredox catalysis, facilitating the facile preparation of various highly functionalized xanthenes. The features of this protocol include high chemo- and regioselectivity, exceptionally mild conditions, a broad substrate scope, scalability to gram-scale quantities, and consistent delivery of good to excellent yields.

Kopsileuconines A-D: Bisindole alkaloids with cytotoxic activity from Kopsia hainanensis.

Kopsileuconines A-D (1-4), four monoterpenoid bisindole alkaloids with unprecedented skeletons, along with their biosynthetically related precursors (5-8) were isolated from the roots of Kopsia hainanensis. Compound 1 possessed an undescribed C-6-C-5' dimerization pattern of aspidofractinine-type alkaloids. Compounds 2-4 were rhazinilam-kopsine (2) and rhazinilam-aspidofractinine type (3 and 4) bisindole alkaloids with undescribed skeletons, respectively.

Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA.

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners.

Asymmetric Total Synthesis of Bufospirostenin A.

The first and asymmetric total synthesis of bioactive bufospirostenin A, an unusual spirostanol with rearranged A/B rings, was accomplished. The synthetically challenging [5-7-6-5] tetracyclic ring system, found in bufospirostenin A and some other natural products, was efficiently constructed by the unique intramolecular rhodium-catalyzed Pauson-Khand reaction of an alkoxyallene-yne. The 11 stereocenters in the final product, including the 10 contiguous stereocenters, were installed diastereoselectively.

Leptosperols A and B, Two Cinnamoylphloroglucinol-Sesquiterpenoid Hybrids from : Structural Elucidation and Biomimetic Synthesis.

Leptosperols A and B ( and ), two cinnamoylphloroglucinol-sesquiterpenoid hybrids featuring unprecedented 1-benzyl-2-(2-phenylethyl) cyclodecane and 2-benzyl-3-phenylethyl decahydronaphthalene backbones, along with their biosynthetic precursor (), were isolated from . Compounds and represent the first example of phloroglucinol derivatives biogenetically constructed by a De Mayo reaction. The biomimetic synthesis of leptosperol B () was achieved using the proposed biosynthetic pathway.

Isolation, Structure Elucidation, and Total Synthesis of Myrtuspirone A from Myrtus communis.

A pair of enantiomeric triketone-phloroglucinol hybrids, (+)- and (-)-myrtuspirone A (1), featuring an unprecedented 3-isopropyl-3 H-spiro[benzofuran-2,1'-cyclohexane] backbone, were isolated from the leaves of Myrtus communis. The absolute configuration of each enantiomer of 1 was determined by X-ray diffraction and chemical calculations. Furthermore, the gram-scale total syntheses of (±)-1 and (-)-1 were conducted in four steps using a Michael- N-iodosuccinimide (NIS)-mediated (3 + 2)-annulation reaction.

Gelsecorydines A-E, Five Gelsedine-Corynanthe-Type Bisindole Alkaloids from the Fruits of Gelsemium elegans.

Five monoterpenoid bisindole alkaloids with new carbon skeletons, gelsecorydines A-E (1-5), together with their biogenetic precursors were isolated from the fruits of Gelsemium elegans. Compounds 1-5 represent the first examples of heterodimeric frameworks composed of a gelsedine-type alkaloid and a modified corynanthe-type one. Notably, compound 2 featured an unprecedented caged skeleton with a 6/5/7/6/5/6 heterohexacyclic ring system, which possessed a pyridine ring that linked the two monomers.

Catalytic asymmetric total syntheses of myrtucommuacetalone, myrtucommuacetalone B, and callistrilones A, C, D and E.

Herein, we describe a concise catalytic approach to the first asymmetric total syntheses of myrtucommuacetalone, myrtucommuacetalone B, and callistrilones A, C, D and E. The syntheses proceed in only 5-7 steps from the readily available compound , without the need for protecting groups. Key features of the syntheses include a unique organocatalytic asymmetric Friedel-Crafts-type Michael addition with high enantioselectivity and a broad substrate scope, a novel Michael-ketalization-annulation cascade reaction, and an oxidative [3 + 2] cycloaddition.