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.

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.

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.

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.

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.

Polydiacetylene liposomes with phenylboronic acid tags: a fluorescence turn-on sensor for sialic acid detection and cell-surface glycan imaging.

Sialic acid (SA) located at the terminal end of glycans on cell membranes has been shown to play an important yet distinctive role in various biological and pathological processes. Effective methods for the facile, sensitive and in situ analysis of SA on living cell surfaces are of great significance in terms of clinical diagnostics and therapeutics. Here, a new polydiacetylene (PDA) liposome-based sensor system bearing phenylboronic acid (PBA) and 1,8-naphthalimide derived fluorophore moieties was developed as a fluorescence turn-on sensor for the detection of free SA in aqueous solution and the in situ imaging of SA-terminated glycans on living cell surfaces. In the sensor system, three diacetylene monomers, PCDA-pBA, PCDA-Nap and PCDA-EA, were designed and synthesized to construct the composite PDA liposome sensor. The monomer PCDA-pBA modified with PBA molecules was employed as a receptor for SA recognition, while the monomer PCDA-Nap containing a 1,8-naphthalimide derivative fluorophore was used for fluorescence signaling. When the composite PDA liposomes were formed, the energy transfer between the fluorophore and the conjugated backbone could directly quench the fluorescence of the fluorophore. In the presence of additional SA or SA abundant cells, the strong binding of SA with PBA moieties disturbed the pendent side chain conformation, resulting in the fluorescence restoration of the fluorophore. The proposed methods realized the fluorescence turn-on detection of free SA in aqueous solution and the in situ imaging of SA on living MCF-7 cell surfaces. This work provides a new potential tool for simple and selective analysis of SA on living cell membranes.

Asymmetric synthesis of (-)-sedacryptine through a diastereoselective Mannich reaction of N,O-acetals with ketones.

An efficient diastereoselective approach to access the 3-hydroxy-2,6-disubstituted piperidine scaffold 1 has been developed through the Mannich process involving N,O-acetal (2S,3R)-6 and ketones in excellent yield with high diastereoselectivity (dr > 99 : 1). In addition, the utility of this convenient one-pot process is demonstrated by the asymmetric synthesis of (-)-sedacryptine 3.