Total Syntheses of Aurachins A and B

Aurachins A and B are alkaloids having 3-hydroxyquinoline N-oxide cores. An efficient method for the synthesis of 3-hydroxyquinoline N-oxides was established and is amenable to the total syntheses of aurachins A and B. Alkylation of 1-(2-nitrophenyl)butan-2-one with farnesyl bromide took place selectively at the benzylic position, and subsequent treatment of the alkylated product with sodium tert-butoxide in dimethyl sulfoxide gave aurachin B. Alkylation of 1-(2-nitrophenyl)butan-2-one with an epoxy iodide derived from farnesol was used to access aurachin A.     

Divergent Asymmetric Total Synthesis of (−)-Voacafricines A and B

A divergent asymmetric total synthesis of voacafricines A and B, hexacyclic monoterpene indole alkaloids, has been accomplished featuring the following key steps: a) a catalyst-controlled asymmetric Pictet–Spengler reaction of 6-methoxytryptamine with a chiral α-ketoester affording a 1,1-disubstituted tetrahydro-β-carboline in excellent yield and diastereoselectivity; b) oxidative cleavage of a 3,5-disubstituted cyclopentene furnishing a dialdehyde intermediate, which was effectively differentiated through spontaneous cyclization with the neighboring hydroxy and secondary amine functions; c) intramolecular nucleophilic addition of a tertiary amino nitrogen atom to the in situ generated oxonium species generating stereoselectively an unprecedented 8-alkyl octahydro-2H-5,8-methanofuro[2,3-b]azepin-8-ium motif bearing five contiguous stereocenters. The synthesis confirmed the absolute configuration of these two natural products.     

Unified Asymmetric Total Syntheses of (−)-Alotaketals A–D and (−)-Phorbaketal A

The novel tricyclic spiroketal alotane-type sesterterpenoids showed strikingly different biological activities and potency with subtle structural alterations. Asymmetric total syntheses of the tricyclic sesterterpenoids (−)-alotaketals A–D and (−)-phorbaketal A were accomplished [29–31 steps from (−)-malic acid] in a collective way for the first time. The key features of the strategy included 1) a new cascade cyclization of vinyl epoxy δ-keto-alcohols to forge the common tricyclic spiroketal intermediate, 2) a late-stage allylic C−H oxidation, and 3) olefin cross-metathesis to install the different side chains.     

Divergent Total Syntheses of (−)-Daphnezomines A and B and (+)-Dapholdhamine B

The daphnezomine A-type subfamily of Daphniphyllum alkaloids structurally features a unique aza-adamantane core skeleton and anticipates efficient strategies for completing their syntheses to thoroughly investigate their biological activities. Herein, divergent total syntheses of (−)-daphnezomines A and B and (+)-dapholdhamine B have been accomplished in 16–20 steps from a known epoxide via rapid construction of a common core intermediate. The present work features a Ti-mediated radical cyclization to establish the azabicyclo[3.3.1]nonane ring system, an intramolecular Heck reaction to install the bridgehead all-carbon quaternary stereocenter, a tandem deprotection/reduction/keto amine-carbinolamine tautomerization to furnish the aza-adamantane backbone, and an NIS-promoted 6-endo-trig aminocyclization to assemble the (+)-dapholdhamine B backbone.     

Asymmetric Total Synthesis of a Diastereisomer A of Tuxpanolide

α-Alkylidene-β-hydroxy butyrolactones have been attractive and challenging targets for organic synthesis in various laboratories because that not only they are rich in skeletal diversity and stereochemistry complexity but also many of them possess quite intriguing and wide biological activities.[1] A novel class of the phytane-type diterpenoid named Tuxpanolide, bearing α-alkylidene-β-hydroxy-γ-butyrolactone skeleton, was isolated from Perymenium hintonii in Central Mexico by Maldonado and co-wokers in 1998.[2] Now we firstly report the efficient strategy of the stereocontrolled total synthesis of a diastereisomer A of Tuxpanolide.     

Revised Structures of Dehydrostenines A and B: Total Syntheses of (±)-Dehydrostenine A and Structure Assigned to Dehydrostenine B

The first total syntheses of the Stemona alkaloid dehydrostenine A and the structure assigned to dehydrostenine B have been completed from a simple pyrrole substrate in 10 and 11 steps, respectively. Two independent Brønsted-acid-mediated intramolecular Michael additions were exploited to construct the tetracyclic dehydrostenine core. As a result of synthetic studies and associated analysis of the relevant literature, revisions of the structures originally assigned to dehydrostenines A and B are proposed.     

Asymmetric Total Synthesis of Cephanolide A

The first asymmetric total synthesis of cephanolide A, a complex hexacyclic C₁₈ dinorditerpenoid from cephalotaxus sinensis, was achieved. The synthesis features a convergent strategy, which provides a flexible approach to prepare the biogenetically cephalotaxus diterpenoids and structurally related derivatives for biological studies. A mild intramolecular Prins cyclization was developed to construct the central hexahydrofluorenol skeleton (A-B-C ring), which relies on the originally proposed hydroacylation strategy. A remote hydroxy group directed hydrogenation was applied to stereospecifically reduce the tetra-substituted enone unit. A sequence of ring forming steps, including lactonization, cation mediated etherification and Friedel–Crafts cyclization, was efficiently utilized to forge the cage-like skeleton.     

Asymmetric Total Synthesis of Hispidanin A

Asymmetric total synthesis of the dimeric diterpenoid hispidanin A was accomplished by non-catalytic Diels–Alder cycloaddition at room temperature. The synthesis relies on iron-catalyzed coupling to construct a Z-configured trisubstituted alkene, an iron-catalyzed radical cascade to generate a labdane-type diene, and both Yamamoto cationic polyene cyclization and palladium-catalyzed Stille coupling to generate a totarane-type dienophile.     

Total Syntheses of Kopsaporine,Kopsinol and Kopsiloscine A

Kopsia alkaloids represent a complex class of natural products bearing a polycyclic ring system with two or three consecutive quaternary carbon centers. In this article, we report the first total synthesis of Kopsaporine related alkaloids. Features of our structure-unit-based strategy are an intramolecular Pummerer rearrangement induced nucleophilic cyclization/aza-Prins cyclization to construct the highly functional hexahydrocarbazole skeleton, an olefin migration vinylogous alkylation to establish the C20 all-carbon quaternary center, an iridium complex mediated radical addition to fuse the aspidofractine framework, an unprecedented IBX oxidation to introduce the α-hydroxyketone moiety, and a bioinspired retro-Aldol/Aldol reaction to convert kopsaporine to kopsiloscine A.     

Asymmetric Total Syntheses of Di- and Sesquiterpenoids by Catalytic C−C Activation of Cyclopentanones

To show the synthetic utility of the catalytic C−C activation of less strained substrates, described here are the collective and concise syntheses of the natural products (−)-microthecaline A, (−)-leubehanol, (+)-pseudopteroxazole, (+)-seco-pseudopteroxazole, pseudopterosin A–F and G—J aglycones, and (+)-heritonin. The key step in these syntheses involve a Rh-catalyzed C−C/C−H activation cascade of 3-arylcyclopentanones, which provides a rapid and enantioselective route to access the polysubstituted tetrahydronaphthalene cores presented in these natural products. Other important features include 1) the direct C−H amination of the tetralone substrate in the synthesis of (−)-microthecaline A, 2) the use of phosphoric acid to enhance efficiency and regioselectivity for problematic cyclopentanone substrates in the C−C activation reactions, and 3) the direct conversion of serrulatane into amphilectane diterpenes by an allylic cyclodehydrogenation coupling.     

Total Syntheses of 16a’-Homoleurosidine and 16a’-Homovinblastine

Vinblastine has been used in clinic as an anti-cancer agent. Due to its high cytotoxity, generation of vinblastine congeners as safe anti-cancer agents is always the interesting topic in medicinal chemistry. In the previous synthesis of vinblastine, it has been found that a higher energy conformation of vinblastine lacking cytotoxity and inhibition against tubulin polymerization, can be converted to its lower energy natural conformation on heating to 110 oC. The high temperature (110 oC) othe…     

Total Syntheses of the Chlorinated β‐Carboline Alkaloids Bauerine A,B, and C

The first total synthesis of the chlorinated 1‐oxo‐β‐carboline alkaloid bauerine C based on a Japp–Klingemann reaction is reported. An intermediate of this synthesis was converted to the fully aromatic β‐carboline bauerine B, and the related alkaloid bauerine A was prepared in an analogous manner.     

Total Synthesis of (±)-Isocembrene: A Tactic for Both Diene Construction and Macrocycle Formation

Abstract

The total synthesis of (±)-isocembrene 1, a naturally occurring cembrene diterpenoid, has been achieved via a unified, convergent and highly efficient strategy by imploying an intramolecular Stille sp²–sp² macrocyclization as the key step and it presents an ideal opportunity to extend the effectiveness of the tactic for both 1,3-diene construction and macrocycle formation.     

Asymmetric Total Synthesis of Mansonone P and R

An asymmetric total synthesis of mansonone P and R were achieved, in which introduction of hydroxy substituent at position 2 was performed by Sharpless dihydroxylation of sily enol ether.     

Total π-Electron Energy of Phenylenes: Bounds and Approximate Expressions

Summary.  The structure dependence of the total π-electron energy E (and therefore of the thermodynamic stability) of phenylenes is examined. Sharp and narrow upper and lower bounds for E are obtained. The gross part of E (above 99%) is determined by the size of the phenylene molecule, measured by the number h of hexagons. An approximate mathematical form of the dependence of E on h is established. Received March 12, 2001. Accepted April 13, 2001     

Total Syntheses of (−)-Conidiogenone B, (−)-Conidiogenone,and (−)-Conidiogenol

Cyclopianes are novel diterpenes featuring a highly strained 6/5/5/5 tetracyclic core embedded with 6–8 consecutive stereocenters. The concise total syntheses of (−)-conidiogenone B, (−)-conidiogenone, and (−)-conidiogenol have been accomplished in 14–17 steps. The present work features a HAT-mediated alkene–nitrile cyclization to access the cis-biquinane, a Nicholas/Pauson–Khand reaction to construct the linear triquinane, and a Danheiser annulation to afford the congested angular triquinane skeleton.     

Total Syntheses of (−)-Minovincine and (−)-Aspidofractinine through a Sequence of Cascade Reactions

We report 8-step syntheses of (−)-minovincine and (−)-aspidofractinine using easily available and inexpensive reagents and catalyst. A key element of the strategy was the utilization of a sequence of cascade reactions to rapidly construct the penta- and hexacyclic frameworks. These cascade transformations included organocatalytic Michael-aldol condensation, a multistep anionic Michael-S_N2 cascade reaction, and Mannich reaction interrupted Fischer indolization. To streamline the synthetic routes, we also investigated the deliberate use of steric effect to secure various chemo- and regioselective transformations.     

Divergent Total Syntheses of (+)-Vulgarisins A–E

The asymmetric total syntheses of (+)-vulgarisins A–E, which share a rare and highly oxygenated [5-6-4-5] tetracyclic core structure that were isolated from P. vulgaris Linn., have been described for the first time in a divergent manner. Key transformations include: 1) a catalytic asymmetric intramolecular cyclopropanation to forge the A ring bearing desired stereochemistry at C14; 2) a one-pot borylation/conjugate addition process for creation of the C1−C11 bond; 3) a Wolff ring contraction to assemble the bicyclo[3.2.0]heptane subunit (CD rings); and 4) a stereocontrolled pinacol cyclization for construction of the central B ring of the natural products.     

Enantioselective Total Syntheses of Lyconadins A–E through a Palladium-Catalyzed Heck-Type Reaction

A novel palladium-catalyzed Heck-type reaction of thiocarbamates has been designed to construct bridged seven-membered-ring systems that are otherwise challenging to prepare. Taking advantage of this newly developed method, enantioselective syntheses of lyconadins A–E ( 1 – 5 ), lycopecurine ( 6 ), and dehydrolycopecurine ( 7 ) have been realized in a divergent fashion. Our synthetic strategy also features an intramolecular cyclization of a N-chloroamine to forge the C6−N bond, a transannular Mannich-type reaction of a cyclic nitrone to stitch the C4 and C13 together, and a cyclocondensation to deliver the (dihydro-)pyridone motif.