ABSTRACT
We report herein the total syntheses of three marsupellin-family sesquiterpenoids, (±)-acetoxymarsupellone and (±)-marsupellins B and D, in 14-19 steps from our known precursor, making marsupellin A also accessible from marsupellin B through a known procedure. The critical tricyclic framework bearing the challenging C7 bridgehead all-carbon quaternary center is strategically constructed through a Ti-mediated reductive cyclization and semipinacol rearrangement sequence. This study provides a general approach to the syntheses of (ent-)longipinane-type molecules.
ABSTRACT
Herein, we report a formal synthesis of (±)-arborisidine via the creation of Jiao's intermediate with the critical caged structure. Starting from tryptamine, a Pictet-Spengler cyclization forged the piperidine ring, a Pd-catalyzed indole allylation and ring-closing metathesis protocol afforded a bridged aza-bicyclo[3.3.1]nonane moiety, and an intramolecular N-alkylation closed the final pyrrolidine ring. This study provides a new approach to the unique caged framework of arborisidine and relevant alkaloids.
ABSTRACT
The first total synthesis of the Euphorbia diterpenoid pepluacetal is disclosed in both racemic and chiral fashions. The synthesis strategically relies on a photo-induced Wolff rearrangement/lactonization cascade (WRLC) reaction to access the cyclobutane moiety, a ring-closing metathesis/cyclopropanation sequence to rapidly forge the 7-3â bicyclic system, and a late-stage Rh-catalyzed transannular carbenoid insertion to C(sp3)-H bond followed by a Baeyer-Villiger oxidation and ring-opening manipulations to install the side chain. The synthetic route demonstrates excellent stereochemical control on the non-classical concave-face bond formation, remote traceless stereochemical relay and high scalability to provide 20â mg of (+)-pepluacetal.
ABSTRACT
Pepluanol B is a new Euphorbia diterpene with an unprecedented tetracyclic backbone. However, its biogenetic relationship with known Euphorbia diterpenes is unclear. We report herein that its ß-hydroxyl ketone motif could undergo a base-promoted retro-aldol/aldol process in two pathways and afford the skeletons of tigliane- and myrsinane-type Euphorbia diterpenes through the formation of the C8-C14 and C7-C13 bonds, respectively. The retro-aldol/aldol cascade indicates that pepluanol B is possibly a biosynthetic precursor of lathyranes and other relevant dipterpenes.
Subject(s)
Diterpenes , Euphorbia , Phorbols , Molecular Structure , Euphorbia/chemistry , Diterpenes/chemistryABSTRACT
An expedient construction of the 5-6-7 tricyclic core of daphnicyclidin-type alkaloids is described. The synthetically challenging cycloheptanone C ring was constructed via a Tiffeneau-Demjanov ring enlargement reaction from a 5-6-6 tricyclic precursor commonly found in calyciphylline A-type alkaloids. Other key transformations included Davis oxidation, 1,2-addition, oxidation, and dehydration to elaborate the essential cyclcohept-2-enone motif.
ABSTRACT
The first total syntheses of Lycopodium alkaloids phleghenrines A and C have been accomplished in 19 and 18 steps, respectively, relying on three (hetero)-Diels-Alder ([4 + 2]) cycloaddition reactions to forge the cyclic molecular backbone and two ring-expansion reactions to manipulate the ring size. A chiral precursor is synthesized through an auxiliary controlled Diels-Alder reaction, rendering the asymmetric synthesis accessible. The established strategy provides a general approach to the relevant novel Lycopodium alkaloids.
ABSTRACT
The first total syntheses of (±)-catellatolactams A and B, two novel ansamacrolactams, are described in 5 and 8 steps, respectively. The strategy relies on an amidation reaction to couple the acylated Meldrum's acid and an aryl amine, a regioselective C-H insertion to construct the γ-lactam moiety, and an RCM reaction to forge the macrocycles with E-olefin. This concise and scalable synthesis provided over 200 mg of the target molecules.
ABSTRACT
The total synthesis of the indole alkaloid (-)-andranginine has been achieved in 10 steps. Key reactions of the synthesis include a nucleophilic addition of acetylenyl anion to chiral N-sulfinyl imine, an intramolecular N-alkylation reaction to close the C ring, and a dienyne metathesis cascade reaction to construct the DE rings. Meanwhile, 16-epi-(-)-andranginine was also obtained with the developed strategy.
Subject(s)
Imines , Indole Alkaloids , Molecular Structure , StereoisomerismABSTRACT
The first de novo synthesis of 1-hydroxyl allogibberic methyl ester, en route to pharbinilic acid and other bioactive molecules, is accomplished in diastereoselective manner. Key reactions of the synthesis include a Pd-catalyzed Suzuki-Miyaura cross-coupling reaction, a Lewis acid-catalyzed reductive Prins cyclization reaction, and a SmI2-mediated transannular pinacol coupling reaction. The synthesis provides a new avenue to access diverse relevant bioactive molecules.
Subject(s)
Esters , Lewis Acids , CyclizationABSTRACT
The skeleton of lucidumone was constructed through oxidative dearomatization/intramolecular Diels-Alder reaction, Cu-mediated remote C-H hydroxylation, allyl oxidation, acid-promoted dynamic kinetic resolution cyclization, and benzylic oxidation.
Subject(s)
Skeleton , Cyclization , Cycloaddition Reaction , Molecular Structure , Oxidation-ReductionABSTRACT
An intramolecular anaerobic Mukaiyama hydration-initiated tandem reduction/condensation/acyl migration/aromatization reaction was developed, which enabled the rapid construction of indole-fused 8-10 membered lactones starting from cyclic 2-allyl-2-(2-nitrophenyl)-1,3-diketones. A nitro substituent in the substrates acted as both an oxygen source in the Mukaiyama hydration step and a nitrogen source in a tandem indole ring construction step. Our reaction features mild conditions, atom economy, and inexpensive reagents and it can be conveniently scaled up to a gram scale in modest yields. A rational reaction mechanism was also proposed based on previous reports and control experiments.
Subject(s)
Indoles , Lactones , Lactones/chemistryABSTRACT
Described herein is a B(C6 F5 )3 -catalyzed S-H insertion reaction of thiophenols and thiols with α-diazoesters to access valuable α-thioesters. With the established protocol, an array of α-thioester products are generated in moderate to good yields with broad scope and functional group tolerance. In addition, this reaction maintains its high efficiency on gram scale and the product can be easily transformed into other useful motifs. This reaction proceeds under solvent-free conditions at room temperature, and generally finishes in twenty minutes upon magnet stirring, which offers an expedient way for the synthesis of thioether-containing compounds.
Subject(s)
Phenols , Sulfhydryl Compounds , Catalysis , SolventsABSTRACT
It is reported herein that by exploiting the commonly shared bicyclic decahydroquinoline motif, a gold-catalyzed enamide-alkyne cycloisomerization reaction is developed to access tricyclic cores in a simple way. These tricyclic cores further serve as an advanced platform for the divergent enantioselective collective total syntheses of five Lycopodium alkaloids, belonging to three different structural types, in a concise and protecting-group-free fashion. The key transformations in the second phase include: 1)â a transannular reductive Heck cyclization for installation of the azepane ring in fawcettidine, fawcettimine, and lycoposerramineâ Q; 2)â a domino Mukaiyama hydration/Grob fragmentation process for construction of the ten-membered lactam system in phlegmariurineâ B; 3)â a Fukuyama one-pot protocol for the construction of the 2-pyridone motif in lycoposerramineâ R. The newly developed strategy is expected to pave the way for the synthesis of other structurally related Lycopodium alkaloids.
Subject(s)
Alkaloids , Lycopodium , Alkaloids/chemistry , Cyclization , Lycopodium/chemistry , Molecular Structure , StereoisomerismABSTRACT
A direct 1,2-dibromination method of alkenes is realized using 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) as a bromine source. This reaction proceeds under mild reaction conditions without the use of a catalyst and an external oxidant. Various sorts of alkene substrates are transformed into the corresponding 1,2-dibrominated products in good to excellent yields with broad substrate scope and exclusive diastereoselectivity. This method offers a green and practical approach to synthesize vicinal dibromide compounds.
ABSTRACT
Diquinane or bicyclo[3.3.0]octane is a conspicuous structural unit existing in the carbo-frameworks of a wide range of natural products such as alkaloids and terpenoids. These diquinane-containing molecules not merely exhibit intriguing architectures, but also showcase a broad spectrum of significant bioactivities, which draw widespread attention from the global synthetic community. During the past decade, with an aim to accomplish the total syntheses of such specified cornucopias of natural products, a variety of elegant strategies for construction of the diquinane ring system have been disclosed. In this Minireview, the achievements on this subject in the timeline from 2010 to June 2020 are demonstrated and it is discussed how the diquinane unit is strategically forged in the context of the specific target structure. In addition, impacts of the selected works to the field of natural product total synthesis is highlighted and the particular outlook of diquinane-containing natural product synthesis is provided.
ABSTRACT
The first total synthesis of Gardneria oxindole alkaloid (-)-gardmultimine A has been achieved in 19 steps from d-tryptophan in a fully stereocontrolled manner. This synthesis features (1) an Ir-catalyzed regioselective C-H borylation/oxidation sequence to introduce the C12 methoxyl group, (2) a stereocontrolled oxidative rearrangement of indole to construct the spirooxindole motif, and (3) an Au(I)-catalyzed transannular Conia-ene-type 6-exo-dig cyclization to establish the azabicyclo[2.2.2]octane skeleton and the exocyclic E-alkene with exclusive stereoselectivity.
Subject(s)
Tryptophan/chemistry , Catalysis , Cyclization , Molecular Structure , Oxidation-ReductionABSTRACT
A strategy for the synthesis of cis-hydrocarbazole with a C3 quaternary carbon center has been developed through nickel/Lewis acid dual-catalyzed arylcyanation. A wide array of cis-hydrocarbazoles was accessed with high diastereoselectivities and atom economies in a good yield. The rich chemistry of the installed nitrile group was demonstrated in the preparation of tryptamine- and tryptophol-derived cis-hydrocarbazoles.
ABSTRACT
The first total synthesis of the Euphorbia diterpenoid pepluanolâ B in both racemic and enantioenriched form involves 20 steps from a known bicyclic diol. This synthesis features an unprecedented bromo-epoxidation to control the eight-membered-ring conformation. In addition, salient reactions for the construction of the tetracyclic backbone include a sterically challenging aldol reaction to establish the quaternary center, a ring closing metathesis (RCM) to forge the eight-membered ring, and a diastereoselective cyclopropanation to assemble the embedded cyclopropane motif.
Subject(s)
Bridged Bicyclo Compounds/chemistry , Cyclopropanes/chemistry , Diterpenes/chemical synthesis , Cyclization , Diterpenes/chemistry , Molecular Conformation , StereoisomerismABSTRACT
An efficient visible light photoredox catalyzed aerobic deprotection of 1,3-oxathiolanes using organic dye Eosin Y as a photocatalyst is disclosed. The deprotection procedure features the use of a metal-free catalyst, mild conditions, a broad range of substrate scope, and good functional group tolerance. 35 examples were tested under the standard conditions and most of them afforded the deprotected products in modest to high yields.
ABSTRACT
The first asymmetric total synthesis of aspidosperma alkaloid (+)-winchinine B was achieved in 12 steps from commercially available materials. A new synthetic strategy which features an efficient aza-Michael addition, a ruthenium-catalyzed transfer dehydrogenation, and an intramolecular palladium-catalyzed oxidative coupling was adopted to install the ABC tricycle system. A one-pot process involving carbonyl reduction/iminium formation/intramolecular conjugate addition developed by our group was utilized to construct the D ring moiety.