Asymmetric Total Synthesis and Biosynthetic Implications of Perovskones, Hydrangenone, and Hydrangenone B.

Perovskones and hydrangenones are a family of structurally complex triterpenoids that were mainly isolated from the genus Salvia medicinal plants. These isoprenoids exhibit a broad range of biological activities, such as antitumor and antiplasmodial activities. Here, we report the collective total synthesis of perovskone, perovskones C, D, F, hydrangenone, and hydrangenone B. The key strategies in this work include the following: (1) an asymmetric photoenolization/Diels-Alder reaction was developed to construct a tricyclic ring bearing three contiguous quaternary centers, which was used to build the core icetexane skeleton; (2) a bioinspired Diels-Alder reaction of perovskatone D with trans-α-ocimene was applied to stereospecifically generate perovskones; (3) late-stage oxidations and ring forming steps were developed to synthesize perovskones and hydrangenones. Our synthetic work suggests that (1) perovskatone D may serve as the precursor of the biosynthesis of perovskones and (2) the formation of hydrangenone and hydrangenone B, containing a five-membered D ring, may involve an oxidative ring cleavage and ring regeneration process.

Total Synthesis and Structural Revision of Rebaudioside S, a Steviol Glycoside.

The total synthesis of rebaudioside S, a minor steviol glycoside from the leaves of Stevia rebaudiana, was investigated via a modular strategy, culminating not only in the first and highly efficient synthesis of Reb-S and analogues thereof but also in the revision of the originally proposed structure. The modular strategy dictated the application of C2-branched disaccharide Yu donors to forge C-13 steviol glycosidic linkages, posing considerable challenges in stereoselectivity control. Through systematic investigations, the effect of the internal glycosidic linkage configuration on the glycosylation stereoselectivity of 1,2-linked disaccharide donors was disclosed, and the intensified solvent effect by the 4,6-O-benzylidene protecting group was also observed with glucosyl donors. Through the orchestrated application of these favorable effects, the stereoselectivity problems were exquisitely tackled.

The first total synthesis of rebaudioside R.

With easily available monosaccharides and steviol as starting materials, the first total synthesis of rebaudioside R with a xylosyl core in the C13-OH linked sugar chain was accomplished via two distinct approaches. The first approach features the stepwise installation of branch-sugar residues via an order of C2-OH first and then C3-OH of the xylosyl core, laying a firm foundation for the synthesis of analogues with different branch sugars, while the second route features the introduction of the C13 trisaccharide sugar chain via a convergent strategy, securing the overall synthetic efficiency. Through the synthetic study, the effect of protecting groups (PGs) at the vicinal hydroxy group on the reactivity of OH acceptors was illustrated.

Dual-Participation Protecting Group Solves the Anomeric Stereocontrol Problems in Glycosylation Reactions.

The 2,2-dimethyl-2-(ortho-nitrophenyl)acetyl (DMNPA) group permits, via robust neighboring group participation (NGP) or long distance participation (LDP) effects, the stereocontrolled 1,2-trans, 1,2-cis, as well as ß-2,6-dideoxy glycosidic bond generation, while suppressing the undesired orthoester byproduct formation. The robust stereocontrol capability of the DMNPA is due to the dual-participation effect from both the ester functionality and the nitro group, verified by control reactions and DFT calculations and further corroborated by X-ray spectroscopy.

The 2,2-Dimethyl-2-(ortho-nitrophenyl)acetyl (DMNPA) Group: A Novel Protecting Group in Carbohydrate Chemistry.

The 2,2-dimethyl-2-(ortho-nitrophenyl)acetyl (DMNPA) group was introduced to synthetic carbohydrate chemistry as a protecting group (PG) for the first time. Benefiting from a unique chemical structure and novel deprotection conditions, the DMNPA group can be cleaved rapidly and mutually orthogonal to other PGs. Orchestrated application of the DMNPA group with other PGs led to the highly efficient synthesis of the glycan of thornasterside A.

Total synthesis of scutellarin and apigenin 7-O-ß-d-glucuronide.

A general protocol for direct glucuronic linkages formation featuring Au(I)-catalyzed appropriately protected glucuronyl o-alkynylbenzoate-involved glycosylation reaction, as well as a concise approach for easy access of scutellarein prominent for the mild and efficient hydroxyl group installation via borylation-oxidation sequence from flavanone derivative, has been established, based on which a novel route for scutellarin derivatives preparation has been devised. The developed strategies, among which the stepwise deprotection process was also included, guarantee the high whole synthetic efficiency, and definitely will find broad application in diversity-oriented synthesis of bioactive flavonoid glycosides.