Crystalline Porous Organic Frameworks Based on Multiple Dynamic Linkages.

A novel class of crystalline porous materials has been developed utilizing multilevel dynamic linkages, including covalent B-O, dative B←N and hydrogen bonds. Typically, boronic acids undergo in situ condensation to afford B3O3-based units, which further extend to molecular complexes or chains via B←N bonds. The obtained superstructures are subsequently interconnected via hydrogen bonds and π-π interactions, producing crystalline porous organic frameworks (CPOFs). The CPOFs display excellent solution processability, allowing dissolution and subsequent crystallization to their original structures, independent of recrystallization conditions, possibly due to the diverse bond energies of the involved interactions. Significantly, the CPOFs can be synthesized on a gram-scale using cost-effective monomers. In addition, the numerous acidic sites endow the CPOFs with high NH3 capacity, surpassing most porous organic materials and commercial materials.

Gram-scale synthesis of alstoscholarinoid B via a bio-inspired strategy.

Alstoscholarinoid A is a novel rearranged triterpene with an unprecedented 6/6/5/6/6/6 framework and an additional unique C28 → C11-olide F-ring, and displays antihyperuricemic bioactivity. Herein, we report a bio-inspired synthesis of alstoscholarinoid B in a stepwise manner, which is amenable to gram-scale synthesis. The synthesis involved the Chugaev elimination as a key step to realize the migration of the Δ11,12-double bond of oleanolic acid, and also featured a sequential LiHMDS-mediated intramolecular aldol condensation/lactonization to establish the polycyclic ring system. Additionally, a tandem deprotection/aldol condensation/lactonization process under the influence of LiI/2,4,6-collidine for forging the polycyclic scaffold was also serendipitously discovered. Mechanistic studies indicated that lithium carboxylate might function as an inner base for the chemoselective α-deprotonation of the C12-aldehyde.

Enantioselective direct vinylogous Michael addition for constructing enantioenriched γ,γ-dialkyl substituted butyrolactams and octahydroindoles.

A nickel(II)-catalyzed asymmetric direct vinylogous Michael addition of γ-alkyl monosubstituted α,ß-unsaturated butyrolactams to α,ß-unsaturated carbonyl compounds has been disclosed, affording γ,γ-dialkyl substituted butyrolactams in good yields and satisfactory enantioselectivities. A tandem catalytic asymmetric vinylogous Michael addition/intramolecular Michael addition has also been developed based on this reaction, which enabled the construction of enantioenriched octahydroindoles with three consecutive stereogenic carbon centers.

A concise synthesis of herbertenolide.

A concise synthesis of (±)-herbertenolide has been accomplished herein. The strategy relies on a H2O2-mediated oxidative ring contraction of all-substituted cyclic α-formyl ketones for the stereospecific construction of contiguous quaternary carbon centers (CQCCs). Furthermore, a Sc(OTf)3/chiral N,N'-dioxide catalyzed asymmetric Michael addition of benzofuranone to MVK has been optimized for forging a chiral aromatic quaternary carbon center, which enables the formal synthesis of (+)-ent-herbertenolide.

Asymmetric synthesis of 9-alkyl tetrahydroxanthenones via tandem asymmetric Michael/cyclization promoted by chiral phosphoric acid.

A tandem asymmetric Michael-addition/cyclization of cyclic 1,3-dicarbonyl compounds to ß,γ-unsaturated α-ketoesters catalyzed by chiral phosphoric acid is presented. This protocol provides a facile approach for the construction of enantioenriched 9-alkyl tetrahydroxanthenones, an ubiquitous framework found in a number of natural products and pharmaceutical molecules, in high yields with good to high enantioselectivities.

Recent progress in the total synthesis of Strychnos alkaloids.

The fascinating structure of Strychnos alkaloids has evoked immense synthetic interest from the chemical community since the landmark synthesis of strychnine by Woodward. After that, the pursuit of the total synthesis of Strychnos alkaloids has never stopped. In this context, the synthesis of strychnine has become a benchmark for the evaluation of new synthetic strategies. Furthermore, the characteristic structure of these alkaloids has also served as an inspiration for the development of novel synthetic methodologies, which provide new synthetic strategies for the synthesis of Strychnos alkaloids. In this article, the recent progress in the total synthesis of Strychnos alkaloids since 2011 is reviewed, including successful total syntheses and synthetic efforts toward Strychnos alkaloids. According to the key feature employed in the synthesis, the content was categorized into novel synthetic methodologies and innovative strategies based on well-documented methodologies.

Highly Enantioselective Tandem Michael Addition of Tryptamine-Derived Oxindoles to Alkynones: Concise Synthesis of Strychnos Alkaloids.

A highly enantioselective tandem Michael addition of tryptamine-derived oxindoles to alkynones was developed by taking advantage of a chiral N,N'-dioxide Sc(OTf)3 catalyst. The reaction enables the facile preparation of enantioenriched spiro[pyrrolidine-3,3'-oxindole] compounds, which provides a novel strategy for the synthesis of monoterpenoid indole alkaloids. As a demonstration, the asymmetric synthesis of strychnos alkaloids [(-)-tubifoline, (-)-tubifolidine, (-)-dehydrotubifoline] was achieved in 10-11 steps.

Stereospecific Construction of Contiguous Quaternary All-Carbon Centers by Oxidative Ring Contraction.

Oxidative ring contraction of cyclic α-formyl ketones was facilitated by the action of H2 O2 under operationally simple and environmentally benign reaction conditions. The process was highly regioselective and enables stereospecific construction of contiguous quaternary all-carbon centers from stereodefined all-substituted all-cyclic ketones. The asymmetric syntheses of (+)-cuparene and (+)-tochuinyl acetate were also successively achieved by taking advantage of this novel protocol.

Synthesis of naked amino-pyrroloindoline via direct aminocyclization of tryptamine.

The first direct access to unprotected amino-pyrroloindoline via aminocyclization of tryptamine and tryptophan has been described. A variety of structurally diverse amino-pyrroloindolines are furnished by the use of O-(2,4-dinitrophenyl)hydroxylamine (DPH) as the nitrogen source in the presence of catalytic Rh2(esp)2.

Synthetic Modification and Insecticidal Activity of 4-epi-cis-Dihydroagarofuran Derivatives.

To synthesize the fundamental framework of dihydroagarofuran, a novel strategy was devised for constructing the C-ring through a dearomatization reaction using 6-methoxy-1-tetralone as the initial substrate. Subsequently, the dihydroagarofuran skeleton was assembled via two consecutive Michael addition reactions. The conjugated diene and trans-dihydroagarofuran skeleton were modified. The insecticidal activities of 33 compounds against Mythimna separata were evaluated. Compounds 11-5 exhibited an LC50 value of 0.378 mg/mL. The activity exhibited a remarkable 29-fold increase compared to positive control Celangulin V, which was widely recognized as the most renowned natural dihydroagarofuran polyol ester insecticidal active compound. Docking experiments between synthetic compounds and target proteins revealed the shared binding sites with Celangulin V. Structure-activity relationship studies indicated that methyl groups at positions C4 and C10 significantly improved insecticidal activity, while ether groups with linear chains displayed enhanced activity; in particular, the allyl ether group demonstrated optimal efficacy. Furthermore, a three-dimensional quantitative structure-activity relationship model was established to investigate the correlation between the skeletal structure and activity. These research findings provide valuable insights for discovering and developing dihydroagarofuran-like compounds.

Highly enantioselective bromocyclization of tryptamines and its application in the synthesis of (-)-chimonanthine.

A shorter path: A highly enantioselective bromocyclization of tryptamine has been developed using an anionic chiral phase-transfer catalyst. This method provides a direct approach for preparing chiral 3-bromopyrroloindoline from tryptamine, which enables a four-step enantioselective synthesis of (-)-chimonanthine. PG=protecting group.

Catalytic Asymmetric Reverse Prenylation of Indol-2-one Enabled a Synthesis of (-)-Debromoflustramine A.

A catalytic asymmetric nucleophilic reverse prenylation of indol-2-ones in situ generated from 3-bromooxindoles with prenyltributylstannane promoted by Ni(II)/chiral N,N'-dioxide was developed. This reaction provides facile access to C3 reverse-prenylated oxindoles in good to excellent enantioselectivities, which enabled the asymmetric synthesis of debromoflustramine A in five steps.

Asymmetric Synthesis of (+)-Vellosimine Enabled by a Sequential Nucleophilic Addition/Cyclization Process.

Herein, we achieved the asymmetric synthesis of (+)-vellosimine in 13 steps (longest linear sequences, LLS). This synthesis featured a sequential nucleophilic addition/cyclization process, which provided an efficient protocol for synthesizing a range of indole fused azabicyclo[3.3.1]nonane. Additionally, a SmI2-mediated reductive cyclization of ketone with an attached α,ß-unsaturated ester for constructing the strained quinuclidine moiety was also highlighted.

A formal synthesis of (-)-erinacine B enabled by asymmetric organocatalysis.

A unified strategy for accessing the core structure of cyathane diterpenoids has been developed, enabling the formal synthesis of (-)-erinacine B. The key feature includes an organocatalyzed asymmetric intramolecular vinylogous aldol reaction for convergently building up the 5-6-6 tricyclic ring system. This strategy also highlights a hydroxyl-directed cyclopropanation/ring opening sequence to stereoselectively set up 1,4-anti and -cis angular-methyl quaternary carbon centers.

Total synthesis of Akuammiline alkaloid (-)-vincorine via intramolecular oxidative coupling.

An asymmetric total synthesis of the Akuammiline alkaloid (-)-vincorine (18 steps from 5-methoxytryptamine, 5% overall yield) is described. The key steps include Pd-catalyzed direct C-H functionalization of indole derivatives, organocatalyzed asymmetric Michael addition of aldehydes to alkylidene malonates, and intramolecular oxidative coupling between indole and malonate moieties.

Convergent Synthesis of Enantioenriched ortho-Fused Tricyclic Diketones via Catalytic Asymmetric Intramolecular Vinylogous Aldol Condensation.

Herein, we describe a catalytic asymmetric intramolecular vinylogous aldol reaction by taking advantage of dual organocatalysts, which enables convergent synthesis of ortho-fused tricyclic diketones in excellent enantioselectivities and diastereoselectivities. Noteworthy is that the reaction stereoselectively forges three consecutive stereogenic carbon centers including a quaternary one. Density functional theory calculations reveal that the enantioselectivity was facilitated by a transannular hydrogen bonding between the protonated quinuclidine moiety of the chiral aminocatalyst and the diketone fragment of the substrate.

An Asymmetric Synthesis of (+)-Isostrychnine Based on Catalytic Asymmetric Tandem Double Michael Addition.

Herein, a concise asymmetric synthesis of (+)-isostrychnine is achieved in nine longest-linear steps with a 16% overall yield. The key features of this synthesis include the catalytic asymmetric tandem double Michael addition of a tryptamine-derived oxindole to an alkynone to facilely forge the A/B/C ring framework, a one-pot intramolecular dehydrative condensation/lactamization reaction to efficiently establish the E/G ring system, and an allylic diazene rearrangement to introduce the pivotal olefin for the subsequent intramolecular Heck reaction.

Asymmetric Synthesis of ent-Fissistigmatin C.

The asymmetric synthesis of ent-fissistigmatin C is successively accomplished in 12 steps (longest linear sequence (LLS)). Relying on the enantioselective coupling of aliphatic aldehyde with 2-hydroxychalcone promoted by cooperative organocatalysts, the pivotal linkage of ent-fissistigmatin C between the flavonoid and the sesquiterpenoid fragment was stereoselectively established. An unprecedented final-stage radical cascade was also featured in this synthesis, which enabled the simultaneous establishment of the trans-decalin framework via forging two consecutive C-C bonds in one step.

Au(I)-Catalyzed Domino Cyclization of 1,6-Diynes Incorporated with Indole.

We disclose herein a Au(I)-catalyzed domino cyclization of 1,6-diynes incorporated with indole. This protocol enabled the diastereoselective buildup of indole-fused azabicyclo[3.3.1]nonanes from linear precursors. Density functional theory calculations showed that the reaction proceeded via an unprecedented cascade dearomatization/rearomatization/dearomatization process. Independent gradient model analysis revealed that a noncovalent attractive interaction between the distal alkyne and the Au/proximal complex was responsible for the chemoselectivity of the first spirocyclization step.

Total synthesis and absolute stereochemical assignment of (-)-communesin F.

A concise asymmetric total synthesis of (-)-communesin F (∼6% overall yield in the longest linear sequence of 19 steps) is described. It features an unprecedented intramolecular oxidative coupling strategy for the elaboration of the requisite spiro-fused indoline moiety. Other notable elements are the use of TBS-protected (S)-phenylglycinol as a chiral auxiliary to induce the asymmetric formation of the spiro-fused indoline part, the mesylate-mediated formation of its G ring, and the introduction of the A ring at the final stage via intramolecular Staudinger reaction. This intramolecular Staudinger reaction proceeded smoothly at 80 °C, providing an additional example illustrating that twisted amides are more reactive than simple amides. Along with the total synthesis, we were able to assign the absolute configuration of natural communesin F as 6R,7R,8R,9S,11R.