Feiqing Ding

Synthesis of (R)-mellein by a partially reducing iterative polyketide synthase.

Mellein and the related 3,4-dihydroisocoumarins are a family of natural products with interesting biological properties. The mechanisms of dihydroisocoumarin biosynthesis remain largely speculative today. Here we report the synthesis of mellein by a partially reducing iterative polyketide synthase (PR-PKS) as a pentaketide product. Remarkably, despite the head-to-tail homology shared with several fungal and bacterial PR-PKSs, the mellein synthase exhibits a distinct keto reduction pattern in the synthesis of the pentaketide. We present evidence to show that the ketoreductase (KR) domain alone is able to recognize and differentiate the polyketide intermediates, which provides a mechanistic explanation for the programmed keto reduction in these PR-PKSs.

A Short and Highly Efficient Synthesis of l-Ristosamine and l-epi-Daunosamine Glycosides

A highly efficient synthesis of L-ristosamine and L-epi-daunosamine glycosides via BF(3)·OEt(2) promoted tandem hydroamination/glycosylation of 3,4-di-O-acetyl-6-deoxy-L-glucal and L-galactal has been developed. The new method proceeds in a completely stereocontrolled manner within a short reaction time. Preparation of a library of L-ristosamine and L-epi-daunosamine glycosides with potential biochemical applications, by varying each component, exemplified the generality of the reaction.

Interrupted Imino‐Nazarov Cyclization of 1‐Aminopentadienyl Cation and Related Cascade Process

Facile 4π conrotatory imino-Nazarov cyclization of a 1-aminopentadienyl cation generated from condensation an aldehyde and secondary aniline in the presence of a catalytic amount of a Lewis acid has been developed. Silver(I)-catalyzed intramolecular arene trapping of the resulting cyclic oxyallyl cation leads to formation of tricyclic indoline-fused cyclopentanone. The use of lanthanide salts allows transformation after the initial trapping to afford tetrahydroquinoline-fused cyclopentenone in a concise manner.

Directed orthometalation and the asymmetric total synthesis of N-deoxymilitarinone A and torrubiellone B.

A diverted total synthesis (DTS) approach to the total synthesis of pyridone alkaloids N-deoxymilitarinone A (8) and torrubiellone B (10) has been developed. The common intermediate 14 was first assembled by a dual directed orthometalation process using a methoxymethyl group as directed metalation group. Other crucial steps include the assembly of polyenes under aldol condensation for DTS using general and concise strategy and diastereoselective synthesis of the syn-dimethyl array by an Evans aldol reaction.

Triflimide-catalyzed allyl–allyl cross-coupling: a metal-free allylic alkylation

A highly efficient metal-free intermolecular C(sp3)-C(sp3) allyl-allyl cross-coupling protocol between allyl acetates and allyltrimethylsilanes, which proceeded smoothly in the presence of catalytic triflimide to form 1,5-dienes with good to excellent regioselectivity, has been developed.

Direct and Stereoselective Synthesis of 1,3-cis-3- Arylsulphonaminodeoxydisaccharides and Oligosaccharides

The 3-aminoglycosides are ubiquitous in biologically important classes of glycoconjugates and naturally occurring oligosaccharides. Despite the rapid growth in the development of synthetic method of 3-amino glycosides, the current state-of-the art suffers from limited substrate scope, low yields, long reaction times, and anomeric mixtures. This work presents a novel direct method for the synthesis of 1,3-cis-3-arylsulphonaminodeoxydisaccharides and oligosaccharides via α-selective glycosylation and hydroamination of glycal in a one-pot manner. This efficient multicomponent reaction methodology provides ready access to 1,3-cis-3-arylsulphonaminodeoxydisaccharides and oligosaccharides and allows derivatization by variation of each component.

Pathways leading to 3-amino- and 3-nitro-2,3-dideoxy sugars: strategies and synthesis

3-Amino- and 3-nitro-2,3-dideoxy sugars, which are structurally diverse and uncommon sugars bearing an amino substitution on a sugar scaffold, have been shown to play crucial roles in the biological activities of aminoglycoside antibiotics and aminoglycoside containing natural products. Over the past few decades, there have been continuing efforts on the convenient synthesis of monosaccharides and oligosaccharides containing 3-amino- and 3-nitro-2,3-dideoxysugar motifs, beginning from either carbohydrate or non-carbohydrate precursors. This review article is intended to provide an updated overview of the most striking contributions in this field, based on the various strategies to construct the 3-amino sugar ring.

Collective synthesis of 4-hydroxy-2-pyridone alkaloids and their antiproliferation activities.

A collective synthesis of 4-hydroxy-2-pyridone alkaloids--specifically, pretenellin B, prebassianin B, farinosone A, militarione D, pyridovericin, and torrubiellone C--has been achieved. Key steps include using a strategic convergent method to synthesize the densely substituted pyridone key intermediate by Suzuki-Miyaura cross-coupling reaction, a divergent synthesis approach of target molecules by aldol condensation of pyridone intermediate with homologous aldehydes, and an iterative synthesis of homologous aldehydes with all-trans-polyene backbones. Interestingly, among the six tumor cell lines investigated, torrubiellone C was found to induce potent and apoptotic inhibitory activities on Jurkat T cells with IC50 values of 7.05 μM. Hence, this approach could potentially contribute to the synthesis of bioactive small-molecule libraries as well as drug discovery.

Ferrier-Type N-Glycosylation: Synthesis of N-Glycosides of Enone Sugars

A mild and efficient protocol for the stereoselective synthesis of N-glycosides of enone sugars has been developed. The reaction proceeds to provide N-glycosides of enone sugars in moderate to good yields with preferential α-anomeric selectivity. Additionally, applications of the N-glycosides of enone sugar derivatives as precursor to assemble some biochemically functional derivatives have also been explored. This includes the use of N-glycosides of enone sugars as reactive dienophile in asymmetric synthesis of bicyclic adduct through Diels-Alder cycloaddition reaction.

Design and synthesis of multivalent neoglycoconjugates by click conjugations

Summary A highly stereoselective BF3∙OEt2-promoted tandem hydroamination/glycosylation on glycal scaffolds has been developed to form propargyl 3-tosylamino-2,3-dideoxysugars in a one-pot manner. Subsequent construction of multivalent 3-tosylamino-2,3-dideoxyneoglycoconjugates with potential biochemical applications was presented herein involving click conjugations as the key reaction step. The copper-catalyzed regioselective click reaction was tremendously accelerated with assistance of microwave irradiation.