Total synthesis of natural products using a desymmetrization strategy

Total syntheses of SB-203207 (1) and sphingofungin E (2) were accomplished by utilizing an asymmetric desymmetrization strategy to introduce multiple stereogenic centers into meso starting compounds in a single step. Thus, rhodium carbenoid-mediated CH insertion into 3 provided the bicyclo[3.3.0]framework 4 for 1, while organocatalyst-mediated bromolactonization of 5 afforded 6 for the synthesis of 2. Similarly, we utilized desymmetric rhodium nitrenoid-mediated aziridination reaction of 5 to obtain a key intermediate required for a total synthesis of pactamycin (29), a complex aminocyclopentitol antibiotic featuring six contiguous stereogenic centers.     

Recent topics in total syntheses of natural dimeric naphthoquinone derivatives

This digest overviews successful synthetic approaches to natural dimeric 1,4-naphthoquinones. Several natural dimeric 1,4-naphthoquinone derivatives have been isolated from natural sources including plants, bacteria, and fungi. They have diverse structures and attractive biological activities. However, it is difficult to construct the dimeric scaffolds efficiently and selectively, because 1,4-naphthoquinones and their derivatives are highly reactive. Efficient and attractive synthetic methodologies to construct unique dimeric 1,4-naphthoquinone skeletons are reviewed.     

Recent applications of gold-catalyzed cascade reactions in total synthesis of natural product

From the point of the view of the synthetic efficiency, the concept ‘step economy’ was required in total synthesis of natural product. Recently, versatile gold-catalyzed cascade reactions have been developed, and relating reports on practical applications in total synthesis has increased. This digest focuses and summarizes the gold-catalyzed reaction cascades in natural product synthesis during last five years with brief discussion on the reaction mechanism of the key gold-catalyzed cascade transformations.     

Application of desymmetrization protocol for the formal total synthesis of emericellamide B

A highly convergent formal total synthesis of emericellamide B, a 19-membered antibacterial depsipeptide is described. The key feature of the strategy is the generation of four stereogenic centers from a bicyclic precursor via desymmetrization technique and utilization for emericellamide B and related natural product synthesis.     

Recent examples of the use of biocatalysts with high accessibility and availability in natural product synthesis

Utilization of biocatalysts with high accessibility and availability, which have recently been applied in the preparation of enantiomerically enriched starting materials and synthetic intermediates for natural product syntheses (mainly 2013–2017) are summarized in this review. The main contents are as follows: 1) recruitment of biocatalysts for the transformation of organic compounds; 2) special precautions for preparative-scale biocatalytic synthetic experiments; 3) asymmetric reduction of carbonyl substrates; 4) kinetic resolution of alcohol and carboxylate enantiomers; 5) desymmetrization of multifunctional alcohol and carboxylate substrates; and 6) recognition of remote and non-central chirality.     

Recent progress toward the total synthesis of humulanolides

The humulanolides are a series of sesquiterpene lactones, most of which have unique and challenging structure. The humulanolides have exhibited anticancer activity. The combinations of fascinating structural motifs and promising pharmacological properties have prompted significant interest in the synthetic community. In this review, we provide a summary of recent progress regarding the total synthesis of humulanolides.     

Recent topics in the desymmetrization of meso-diols

The desymmetrization of meso compounds is one of the most effective strategies for asymmetric synthesis. This digest focuses on recent progress in the desymmetrization of meso-diols and their derivatives. The topics discussed here include methods for the enzymatic acylation of meso-diols and the hydrolysis of meso-diesters, acylation, related reactions of meso-diols with organocatalysts and metal catalysts, the oxidation of meso-diols by enzymes, organocatalysts, and metal catalysts, and the desymmetrization of meso-dicarbamates with metal catalysts. The desymmetrization of meso-diols using tandem reactions is also discussed.     

Recent topics of the stereodivergent synthesis of natural products

A variety of natural products, a valuable source of drug lead compounds, coexist with their stereoisomers as congeners. For pursuing the structural elucidation and the structure–activity relationship study of natural products, it is needed to establish the streamlined synthetic route to supply natural products and their stereoisomers. Divergent pathway is one of the synthetic strategies to deliver more than one target compound. In this digest, selected examples of the stereodivergent approach toward the synthesis of natural products are described. Especially, this digest focuses on common synthetic intermediates and stereodiversification steps from the common intermediates to reach the target compounds.     

Recent topics in application of selective Rh(II)-catalyzed CH functionalization toward natural product synthesis

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A novel and efficient total synthesis of shikonin

A novel and efficient synthesis of shikonin was accomplished with excellent enantiomeric excess (99.3% ee) and high overall yield (47%) in only six steps. The synthetic strategy involved an efficient Ru(II)-catalyzed asymmetric hydrogenation employing C₂-symmetric planar chiral ruthenocene phosphinooxazoline ligand (L-3), followed by the subsequent removal of the methyl protecting groups. Meanwhile, it could be preliminarily confirmed that the chiral side chain of shikonin was difficult to be constructed in one step with both stereoselectivity and α-regioselectivity.     

Enantioselective synthesis of macrolactone core of the natural product Sch725674

An enantioselective synthesis of the macrolactone core of natural product Sch725674 was accomplished from furfural. Key reactions in assembly of the macrolactone are the use of furan as a but-2-ene-dione equivalent and ring closing metathesis.     

Recent advances in biomimetic natural product synthesis

This review highlights some of the most elegant and instructive biomimetic syntheses of natural products over the last few years, providing an updated overview of this area of research.     

Divergent strategy in natural product total synthesis

Divergent strategy in natural product synthesis allows the comprehensive synthesis of family natural products. Efficient formulation of this idea requires the biosynthetic/biosynthesis-inspired insight toward the well-orchestrated design of a pluripotent late-stage intermediate, in concomitant with the applicability of the intermediates for versatile transformations. This digest focuses on the actual applications of those strategies in natural product synthesis with an emphasis on the recipes for the choice of the common intermediates.     

Chemistry of renieramycins. Part 9: Stereocontrolled total synthesis of (±)-renieramycin G

A 25-step stereocontrolled total synthesis of (±)-renieramycin G (1g) from readily available 2-hydroxy-3-methyl-4,5-dimethoxybenzaldehyde (3) is described. This synthesis features the concise construction of the pentacyclic framework using the stereoselective Pictet-Spengler type cyclization reaction of lactam (14) with ethyl diethoxyacetate, followed by the base-catalyzed isomerization of the C-1 stereo center.     

Solution-phase total synthesis of the hydrophilic natural product argifin using 3,4,5-tris(octadecyloxy)benzyl tag

A solution-phase total synthesis of argifin using 3,4,5-tris(octadecyloxy)benzyl tag as a hydrophobic protective group of carboxylic acid was developed to produce 44% overall yield for 16 linear steps. Argifin, a novel class of natural product chitinase inhibitor, is a highly water-soluble cyclic pentapeptide, so hitherto, only solid-phase synthesis techniques have been used to conveniently prepare the compound and its derivatives. 3,4,5-Tris(octadecyloxy)benzyl alcohol (HO-TAGa) and its esters are highly crystalline materials and highly capable of dissolving in less-polar solvents such as dichloromethane, benzene, THF, etc., but insoluble in polar solvents such as methanol and DMSO. The combination of HO-TAGa and Fmoc-based peptide synthesis, together with simple purification by recrystallization from MeOH solution, furnished an efficient and practical route of argifin production in the liquid-phase.     

Setbacks and hopes: en route to the synthesis of uncialamycin

We herein report a new approach toward the synthesis of uncialamycin, an enediyne natural product isolated from the Streptomyces uncialis, bacteria present on the surface of the lichen Cladonia uncialis. A model for the preparation of uncialamycin has been achieved through a reaction cascade, an acetylide addition to the activated quinoline moiety, and a ring closure reaction as key steps.     

Chemoenzymatic total synthesis of cryptocaryalactone natural products

A new chemoenzymatic route for the preparation of cryptocaryalactones natural products using a kinetic resolution process as the key step is described. Novozyme-435 catalyzed hydrolysis of the prochiral (±)-monoester 7 afforded the precursors of cryptocaryalactones with high enantiomeric excess and excellent yields. The compounds (4S,6S)-7 and (4R,6R)-7 were converted to (+)-(6R,2′S)-cryptocaryalactone (1) and (?)-(6S,2′R)-cryptocaryalactone (2), respectively by employing Wittig-olefination, lactonization and acylation reactions.     

Formal total synthesis of borrelidin: synthesis of C1-C11 fragment via desymmetrization strategy

A stereoselective formal total synthesis of borrelidin is described. The synthetic strategy for synthesis of C1-C11 fragment features desymmetrization of Diels-Alder adduct, Sharpless asymmetric epoxidation, regioselective opening of chiral epoxide, and alkylation using Evans chiral auxiliary.