Forging the Tetracyclic Core Framework of Rhodomolleins XIV and XLII: A Ring-Distortion Approach.

A ring distortion approach for the synthesis of an advanced intermediate en route to rhodomolleins XIV and XLII was described, which led to successful construction of the 5/8/5/5 tetracyclic core framework of the kalmane diterpenoids. Key steps of the strategy include an oxidative dearomatization-induced (ODI)-Diels-Alder cycloaddition, a Dowd-Beckwith rearrangement, and a bioinspired Wagner-Meerwein rearrangement.

Haplotype analysis and marker development of five salt-tolerant-related genes in rice (Oryza sativa L.).

Salinity stress is a great threat to the growth and productivity of crops, and development of salt-tolerant crops is of great necessity to ensure food security. Although a few genes with natural variations that confer salt tolerance at germination and seedling stage in rice have been cloned, effective intragenic markers for these genes are awaited to be developed, which hinder the use of these genes in genetic improvement of salt tolerance in rice. In this study, we first performed haplotype analysis of five rice salt-tolerant-related genes using 38 rice accessions with reference genome and 4,726 rice germplasm accessions with imputed genotypes and classified main haplotype groups and haplotypes. Subsequently, we identified unique variations for elite haplotypes reported in previous studies and developed 11 effective intragenic makers. Finally, we conducted genotyping of 533 of the 4,726 rice accessions from worldwide and 70 approved temperate geng/japonica cultivars in China using the developed markers. These results could provide effective donors and markers of salt-tolerant-related genes and thus could be of great use in genetic improvement of salt tolerance in rice.

Total Synthesis of (-)-Retigeranic Acid A: A Reductive Skeletal Rearrangement Strategy.

The asymmetric total synthesis of (-)-retigeranic acid A was described, which relies on a crucial reductive skeletal rearrangement cascade for the controllable assembly of diverse angular triquinane subunits. Taken together with an intramolecular Michael/aldol cyclization, an ODI-[5 + 2] cycloaddition/pinacol rearrangement cascade, a Wolff ring contraction and a stereoselective HAT reduction, our synthetic approach has enabled the access to (-)-retigeranic acid A in a concise and practical manner.

Divergent Synthetic Approach to Grayanane Diterpenoids.

The total syntheses of nine grayanane diterpenoids, namely, GTX-II (1), GTX-III (2), rhodojaponin III (3), GTX-XV (4), principinol D (5), iso-GTX-II (6), 1,5-seco-GTX-Δ1,10-ene (7), and leucothols B (8) and D (9), that belong to five distinct subtypes, were disclosed in a divergent manner. Among them, six members were accomplished for the first time. The concise synthetic approach features three key transformations: (1) an oxidative dearomatization-induced [5 + 2] cycloaddition/pinacol rearrangement cascade to assemble the bicyclo[3.2.1]octane carbon framework (CD rings); (2) a photosantonin rearrangement to build up the 5/7 bicycle (AB rings) of 1-epi-grayanoids; and (3) a Grob fragmentation/carbonyl-ene process to access four additional subtypes of grayanane skeletons. Density functional theory calculations were performed to elucidate the mechanistic origins of the crucial divergent transformation, which combined with late-stage synthetic findings provided insights into the biosynthetic relationships between these diverse skeletons.

Divergent Total Syntheses of (+)-Vulgarisins†A-E.

The asymmetric total syntheses of (+)-vulgarisins A-E, which share a rare and highly oxygenated [5-6-4-5] tetracyclic core structure that were isolated from P. vulgaris Linn., have been described for the first time in a divergent manner. Key transformations include: 1) a catalytic asymmetric intramolecular cyclopropanation to forge the A ring bearing desired stereochemistry at C14; 2) a one-pot borylation/conjugate addition process for creation of the C1-C11 bond; 3) a Wolff ring contraction to assemble the bicyclo[3.2.0]heptane subunit (CD rings); and 4) a stereocontrolled pinacol cyclization for construction of the central B ring of the natural products.

Transcriptome Dynamic Analysis Reveals New Candidate Genes Associated with Resistance to Fusarium Head Blight in Two Chinese Contrasting Wheat Genotypes.

In recent years, Fusarium head blight (FHB) has developed into a global disease that seriously affects the yield and quality of wheat. Effective measures to solve this problem include exploring disease-resistant genes and breeding disease-resistant varieties. In this study, we conducted a comparative transcriptome analysis to identify the important genes that are differentially expressed in FHB medium-resistant (Nankang 1) and FHB medium-susceptible (Shannong 102) wheat varieties for various periods after Fusarium graminearum infection using RNA-seq technology. In total, 96,628 differentially expressed genes (DEGs) were identified, 42,767 from Shannong 102 and 53,861 from Nankang 1 (FDR < 0.05 and |log2FC| > 1). Of these, 5754 and 6841 genes were found to be shared among the three time points in Shannong 102 and Nankang 1, respectively. After inoculation for 48 h, the number of upregulated genes in Nankang 1 was significantly lower than that of Shannong 102, but at 96 h, the number of DEGs in Nankang 1 was higher than that in Shannong 102. This indicated that Shannong 102 and Nankang 1 had different defensive responses to F. graminearum in the early stages of infection. By comparing the DEGs, there were 2282 genes shared at the three time points between the two strains. GO and KEGG analyses of these DEGs showed that the following pathways were associated with disease resistance genes: response to stimulus pathway in GO, glutathione metabolism, phenylpropanoid biosynthesis, plant hormone signal transduction, and plant-pathogen interaction in KEGG. Among them, 16 upregulated genes were identified in the plant-pathogen interaction pathway. There were five upregulated genes, TraesCS5A02G439700, TraesCS5B02G442900, TraesCS5B02G443300, TraesCS5B02G443400, and TraesCS5D02G446900, with significantly higher expression levels in Nankang 1 than in Shannong 102, and these genes may have an important role in regulating the resistance of Nankang 1 to F. graminearum infection. The PR proteins they encode are PR protein 1-9, PR protein 1-6, PR protein 1-7, PR protein 1-7, and PR protein 1-like. In addition, the number of DEGs in Nankang 1 was higher than that in Shannong 102 on almost all chromosomes, except chromosomes 1A and 3D, but especially on chromosomes 6B, 4B, 3B, and 5A. These results indicate that gene expression and the genetic background must be considered for FHB resistance in wheat breeding.

Large-Scale Heat-Tolerance Screening and Genetic Diversity of Pea (Pisum sativum L.) Germplasms.

Pea (Pisum sativum L.) is an important legume crop. However, the yield of pea is adversely affected by heat stress in China. In this study, heat-tolerant germplasms were screened and evaluated in the field under multi-conditions. The results showed that heat stress could significantly affect pea yield. On the basis of grain weight per plant, 257 heat-tolerant and 175 heat-sensitive accessions were obtained from the first year's screening, and 26 extremely heat-tolerant and 19 extremely heat-sensitive accessions were finally obtained in this study. Based on SNaPshot technology, two sets of SNP markers, including 46 neutral and 20 heat-tolerance-related markers, were used to evaluate the genetic diversity and population genetic structure of the 432 pea accessions obtained from the first year's screening. Genetic diversity analysis showed that the average polymorphic information content was lower using heat-tolerance-related markers than neutral markers because of the selective pressure under heat stress. In addition, population genetic structure analysis showed that neutral markers divided the 432 pea accessions into two subpopulations associated with sowing date type and geographical origin, while the heat-tolerance-related markers divided these germplasms into two subpopulations associated with heat tolerance and sowing date type. Overall, we present a comprehensive resource of heat-tolerant and heat-sensitive pea accessions through heat-tolerance screenings in multi-conditions, which could help genetic improvements of pea in the future.

Improved pea reference genome and pan-genome highlight genomic features and evolutionary characteristics.

Complete and accurate reference genomes and annotations provide fundamental resources for functional genomics and crop breeding. Here we report a de novo assembly and annotation of a pea cultivar ZW6 with contig N50 of 8.98 Mb, which features a 243-fold increase in contig length and evident improvements in the continuity and quality of sequence in complex repeat regions compared with the existing one. Genome diversity of 118 cultivated and wild pea demonstrated that Pisum abyssinicum is a separate species different from P. fulvum and P. sativum within Pisum. Quantitative trait locus analyses uncovered two known Mendel's genes related to stem length (Le/le) and seed shape (R/r) as well as some candidate genes for pod form studied by Mendel. A pan-genome of 116 pea accessions was constructed, and pan-genes preferred in P. abyssinicum and P. fulvum showed distinct functional enrichment, indicating the potential value of them as pea breeding resources in the future.

Development and Application of Intragenic Markers for 14 Nitrogen-Use Efficiency Genes in Rice (Oryza sativa L.).

Asian cultivated rice consists of two main subspecies, xian/indica (XI) and geng/japonica (GJ), and GJ accessions have significantly lower nitrogen-use efficiency (NUE) than XI accessions. In order to facilitate genetic improvement of NUE in GJ accessions, we conducted haplotype analysis of 14 cloned NUE genes using 36 rice germplasm accessions with high-quality reference genome and developed 18 intragenic markers for elite haplotypes, which were then used to evaluate NUE genes in another 41 genetically diverse germplasm accessions from 12 countries and 71 approved GJ cultivars from northern provinces of China. Our results show that elite haplotypes of 12 NUE genes are mainly existed in XI accessions, but few is distributed in GJ accessions. The number of elite haplotypes carried by an XI accession can reach 10, while that carried by a GJ accession is less than 3. Surprisingly, the elite haplotype of gene DEP1 is nearly fixed in approved GJ cultivars, and elite haplotypes of gene MYB61 and NGR5 have been introduced into some approved GJ cultivars. The developed intragenic markers for NUE genes and evaluated 77 genetically diverse rice accessions could be of great use in the improvement of NUE in GJ cultivars.

Divergent Total Syntheses of (-)-Crinipellins Facilitated by a HAT-Initiated Dowd-Beckwith Rearrangement.

A hydrogen atom transfer (HAT)-initiated Dowd-Beckwith rearrangement reaction was developed, which enables the efficient assembly of diversely functionalized polyquinane frameworks. By incorporation of an iridium-catalyzed regio- and enantioselective hydrogenation and a diastereocontrolled ODI-[5+2] cycloaddition/pinacol rearrangement cascade reaction, the asymmetric total syntheses of eight tetraquinane natural products, including (-)-crinipellins A-F and (-)-dihydrocrinipellins A and B, have been achieved in a concise and divergent manner.

Cascade Cyclization of Azadienes with Difluoroenoxysilanes: A One-Pot Formal [4 + 2] Approach to Fluorinated Polyfused Heterocycles.

A TfOH-promoted synthesis of fluorinated polyfused heterocycles via the cascade cyclization of azadienes and difluoroenoxysilanes has been developed, leading to the facile construction of fluorinated benzofuro[3,2-b]pyridines, 5H-indeno[1,2-b]pyridines, and 5,6-dihydrobenzo[h]quinolines. This one-pot formal [4 + 2] approach involves 1,4-difluoroalkylation, desulfonylation, cyclization, and dehydrated and dehydrofluorinated aromatization and represents the first application of difluoroenoxysilane in cascade transformations. Furthermore, this methodology is highlighted by the synthesis of three fluoro analogues of bioactive molecules with potent topoisomerase inhibitory activities.

Electrochemical ODI-[5+2] Cascade for the Syntheses of Diversely Functionalized Bicyclo[3.2.1]octane Frameworks.

A metal- and hypervalent iodine reagent-free electrochemical oxidative dearomatization-induced [5+2] cycloaddition/pinacol rearrangement cascade reaction was described. The electrosynthetic method showed strong tolerance for vinylphenols, ethynylphenols, and allenylphenols, which thus enabled the rapid assembly of diversely functionalized bicyclo[3.2.1]octanes in 41-95% yields and up to >20:1 dr. This protocol could be scaled up to gram amounts and should find wide application in complex natural product synthesis.

Asymmetric Total Syntheses of (+)-Davisinol and (+)-18-Benzoyldavisinol: A HAT-Initiated Transannular Redox Radical Approach.

The first and asymmetric total syntheses of two C11-oxygenated hetisine-type diterpenoid alkaloids, namely, (+)-davisinol and (+)-18-benzoyldavisinol, is described. The concise synthetic approach features a HAT-initiated transannular redox radical cyclization, an ODI-Diels-Alder cycloaddition, and an acylative kinetic resolution. By incorporating an efficient late-stage assembly of the azabicycle, our strategy would streamline the synthetic design of C20-diterpenoid alkaloids and pave the way for their modular syntheses.

Asymmetric Total Syntheses of 8,9-Seco-ent-kaurane Diterpenoids Enabled by an Electrochemical ODI-[5+2] Cascade.

An electrochemical ODI-[5+2] cascade reaction was developed which enables the rapid assembly of diversely functionalized bicyclo[3.2.1]octadienones from sensitive ethynylphenols. By combining a directed retro-aldol/aldol process, a [2,3]-sigmatropic rearrangement, and an Al(O-iPr)3 -promoted reductive 1,3-transposition, the asymmetric total syntheses of five 8,9-seco-ent-kauranoids-(-)-shikoccin, (-)-O-methylshikoccin, (-)-epoxyshikoccin, (+)-O-methylepoxyshikoccin, and (+)-rabdo-hakusin-have been achieved in a concise and efficient manner.

Total Synthesis of (+)-Alsmaphorazine†C and Formal Synthesis of (+)-Strictamine: A Photo-Fries Approach.

A bioinspired photo-Fries/imine capture cascade reaction was developed in continuous-flow mode, which facilitated the rapid construction of a series of diversely functionalized 2,7-heterocycle-fused tetrahydrocarbazoles, the ubiquitous core structures embedded in strychnos and akuammiline-type monoterpene indole alkaloids. The synthetic utility of this novel method has been preliminarily explored by the first total synthesis of (+)-alsmaphorazine C and formal synthesis of (+)-strictamine in a concise and efficient manner.

HFIP-catalyzed direct dehydroxydifluoroalkylation of benzylic and allylic alcohols with difluoroenoxysilanes.

Hexafluoroisopropanol (HFIP)-catalyzed direct dehydroxydifluoroalkylation of benzylic and allylic alcohols with difluoroenoxysilanes is developed. This procedure enables the synthesis of a broad range of α,α-difluoroketones, a class of highly valuable intermediates and building blocks in medicinal and organic chemistry. Here, we have demonstrated for the first time that HFIP could act as a powerful catalyst for fluorinated carbon-carbon bond formation. The application of this protocol in late-stage dehydroxydifluoroalkylation of potentially bioactive drugs and natural products has also been carried out.

Tetracyclic Diterpenoid Synthesis Facilitated by ODI-Cascade Approaches to Bicyclo[3.2.1]octane Skeletons.

Tetracyclic diterpenoids (C20) mainly refer to the plant terpenoids bearing biogenetically related carbon skeletons derived from copalyl diphosphates (ent-CPP and syn-CPP). This large family contains over 1600 known members that can be categorized into 11 major structural types. Among them, more than three-quarters share a bridged bicyclo[3.2.1]octane subunit, which is also an important branching point in biosynthesis en route to the other types of bicyclic scaffolds, such as bicyclo[2.2.2]-, bicyclo[3.3.0]-, and tricyclo[3.2.1.0]octanes. Combined with the significance of its stereochemical importance in biological activity, the assembly of the bicyclo[3.2.1]octane skeletons is critical to the success of the whole synthesis blueprint toward tetracyclic diterpenoids. Although a number of inspiring methodologies have been disclosed, general approaches by the incorporation of innovative cascade reactions permitting access to diverse structural types of tetracyclic diterpenoids remain limited and in urgent demand.Because of the long-standing interest in the synthesis of bridged diterpenoids, we have recently developed two complementary types of oxidative dearomatization induced (ODI) cascade approaches to the rapid and efficient construction of bicyclo[3.2.1]octane skeletons. In this Account, we summarize our original synthesis design, methodology development, and the application of these two strategies in tetracyclic diterpenoid synthesis during the past few years in our laboratory.First, we detail our preliminary investigation of the ODI-[5 + 2] cycloaddition/pinacol rearrangement cascade reaction, which showed a wide scope of vinylphenol substrates and led to cyclopentane and cyclohexane-fused bicyclo[3.2.1]octanes in good yields with excellent dr values. Next, we describe the utilization of this ODI-[5 + 2] cascade reaction which resulted in the asymmetric total syntheses of four highly oxygenated ent-kauranoids. The strategy concerning accurate stereochemical control in the ODI-[5 + 2] cycloaddition was then successfully transplanted to the total syntheses of three stemaranoids, thus providing a straightforward and diastereoselective route to C9-ethano-bridged tetracyclic diterpenoids. To access more complex diterpenoid rhodomollanol A, we exploited two additional biomimetic rearrangements, namely, the retro-Dieckmann fragmentation/vinylogous Dieckmann cyclization cascade and the photo-Nazarov cyclization/intramolecular cycloetherification cascade. Taken together with the ODI-[5 + 2] cascade, the asymmetric total synthesis of the target molecule was realized, which shed light on the biogenetic pathway of the unprecedented rhodomollane-type carbon framework. Finally, we describe an ODI-Diels-Alder/Beckwith-Dowd cascade approach as a valuable supplement to the ODI-[5 + 2] cascade for the fabrication of cycloheptane-fused bicyclo[3.2.1]octane skeletons. Its versatility was also demonstrated by the total syntheses of two challenging grayanane diterpenoids. In view of the high functional-group compatibility and scalability, we anticipate that the two novel cascade approaches will find further use in the field of complex natural product synthesis.

Integrative analyses of transcriptomics and metabolomics upon seed germination of foxtail millet in response to salinity.

Salinity stress has become an expanding threat to food security worldwide. Revealing the mechanisms of salinity tolerance in plants has immense significance. Foxtail millet (Setaria italica L.) has been regarded as a model crop for exploring mechanisms under stress, considering its extreme adaptation abilities to adverse ecologies. In present study, two foxtail millet cultivars of Yugu2 and An04 with contrasting salt tolerance properties were investigated through integrative analyses of transcriptomics and metabolomics. In the transcriptomics results, 8887 and 12,249 DEGs were identified in Yugu2 and An04 in response to salinity, respectively, and 3149 of which were overlapped between two varieties. These salinity-responsive genes indicated that ion transport, redox homeostasis, phytohormone metabolism, signaling and secondary metabolism were enriched in Yugu2 by GO and KEGG analyses. The integrative omics analysis implied that phenylpropanoid, flavonoid and lignin biosynthesis pathways, and lysophospholipids were vital in determining the foxtail millet salinity tolerance. Importantly, the tolerance of Yugu2 attributed to higher efficiencies of ion channel and antioxidant system. All these provide a comprehensive regulatory network of foxtail millet to cope with salinity, and shed some lights on salt tolerance which is relevant for other cereal crops.

Palladium-Catalyzed Tandem Dehydrogenative [4 + 2] Annulation of Terminal Olefins with N-Sulfonyl Amides via C-H Activations.

A palladium-catalyzed tandem dehydrogenative [4 + 2] annulation of terminal olefins with N-sulfonyl amides via C(sp2)-H activation, allylic C(sp3)-H activation, and homoallylic C(sp3)-H elimination processes has been developed. Promoted by the DMSO ligand, various benzamides, heterocyclic arylamides, alkenyl carboxamides, and commercial olefins are found to be efficient substrates to construct important heterocyclic compounds bearing a vinyl substituent with high E stereoselectivity. Using air as the terminal oxidant also provides a great advantage regarding environmental friendliness.