Multienzyme Cascade Catalyzed Skeleton Rearrangement in a Caged Polyketide Biosynthesis.

Rearrangement of the skeleton is crucial for improving the structural complexity and diversity of type II polyketide natural products. In this study, we investigated the rearrangement process from a planar aromatic tetracyclic intermediate to the caged lactones, which is managed by five oxidoreductases. We chemically synthesized the proposed linear tetracyclic substrate, validated the transformation process through and experiments, and elucidated the enzyme-catalyzed mechanism using isotope labeling.

Curative effect analysis of robot-assisted drainage surgery in treatment of spontaneous hypertensive brainstem hemorrhage.

Objective: Spontaneous hypertensive brainstem hemorrhage (HBSH) is characterized by sudden onset, rapid progression and poor prognosis. There has been a growing tendency of surgical treatment for HBSH. This study aimed to investigate outcomes and potential factors associated with the prognosis of robot-assisted drainage surgery for HBSH treatment.

Biomimetic Synthesis of Chejuenolides A-C by a Cryptic Lactone-Based Macrocyclization: Stereochemical Implications in Biosynthesis.

A hypothetical Mannich macrocyclization in the biosynthesis of chejuenolides A-C served as the basis for the synthetic design herein. Using a lactone-based linear precursor constructed via a tactic sequence of aldol-Julia-aldol reactions on a gram scale, the biomimetic total synthesis and structural validation of chejuenolides A-C were successfully achieved for the first time. The β-oxo-δ-lactone unit in the macrocyclized adducts was fragile and readily converted to a series of C2/C18-diastereoisomers via a decarboxylation and protonation pathway.

First report of Stenotrophomonas maltophilia causing root soft rot of Sanqi (Panax notoginseng) in China.

Sanqi (Panax notoginseng (Burk.) F. H.

The Fruit of Gold: Biomimicry in the Syntheses of Lankacidins.

Natural products are constructed by organisms in impressive ways through various highly selective enzyme-catalyzed chemical reactions. Over the past century, there has been considerable interest in understanding and emulating the underlying biosynthetic logic for the target molecule. The successful implementation of a biomimetic strategy usually has some uniquely valuable benefits over other abiotic routes in total synthesis by (1) corroborating the chemical feasibility of a given biogenetic hypothesis and further unraveling some insightful implications for future biosynthetic studies and (2) providing remarkably more concise access to not only the original synthetic target but also diversified biogenetically related congeners, which may result in either the structural reassignment of previously disclosed natural products or the anticipation of undiscovered natural products.

First report of wild tomato mosaic virus infecting chilli pepper in China.

Chilli pepper is an important economic crop and virus diseases are constraints on its production. In 2018, disease surveys were conducted at a 15-ha chilli pepper plantation in Dehong, southwest of Yunnan Province, China. Throughout the chilli pepper growing season from March to September, pepper plants developed three different virus-like symptoms on leaves, including mosaic, yellow mottle and shrinkage (Fig.

Stereodivergent Synthesis of Lankacyclinol and Its C2/C18-Congeners Enabled by a Bioinspired Mannich Reaction.

Lankacidin-group antibiotics are complex polyketides typically with a synthetically challenging 17-membered carbocyclic ring. Herein we evolved an alternative palladium-catalyzed coupling-based strategy for constructing this structural moiety. After assembling the two advanced fragments under basic conditions in a biphasic system, of the four possible Mannich adducts, two separable adducts bearing identical C2-stereochemistries were formed in high combined yields, and the ratio of them can be altered by changing the reaction conditions from dichloromethane and 23 °C (18/18, 1.

Landscape of Lankacidin Biomimetic Synthesis: Structural Revisions and Biogenetic Implications.

In this report, a unified biomimetic approach to all known macrocyclic lankacidins is presented. By taking advantage of the thermolysis of ,-acetal to generate the requisite -acyl-1-azahexatriene species, we eventually realized the biomimetic Mannich macrocyclization, from which all of the macrocyclic lankacidins can be conquered by orchestrated desilylation. The reassignments of the reported structures of isolankacidinol ( to ) and the discovery of a recently isolated "lankacyclinol" found to be in fact 2,18-bis--lankacyclinol () unraveled the previously underappreciated chemical diversity exhibited by the enzymatic macrocyclization.

Postulated Biogenesis-Guided Total Synthesis and Structural Revision of 2,18--Lankacidinol A.

The macrocyclic structure of 2,18--lankacidinol A, a newly isolated antitumor antibiotic, has been revised on the basis of a concise modular synthesis inspired by a reconsidered biosynthetic proposal. Notable features include (1) an acid-promoted intramolecular transacetalization of a -lactoyl--methyl-,-acetal to construct the 4-oxazolidinone ring and (2) late-stage β-keto imide aldolizations that give rise to facile, stereodivergent access to all lactonic diastereomers.

Stereoconfining macrocyclizations in the total synthesis of natural products.

Covering: selected examples in the past three decades (up to 2018) The challenging structures and often potent biological activities of naturally occurring macrocycles have attracted much attention among the synthetic community. In a typical retrosynthetic disconnection, commonly used macrocyclization tactics, including macrolactonization, macrolactamization, ring-closing metathesis, olefination, and metal-mediated cross-coupling reactions, are invariably based on linear substrates in which all of the stereogenic centers have already been set forth. Macrocyclizations with the simultaneous installation of the requisite stereogenic centers can be advantageous with respect to a broader substrate spectrum as well as a usually higher overall synthetic efficiency.

Biomimetic Synthesis of Lankacidin Antibiotics.

We devised short syntheses of lankacidinol and lankacyclinol that feature biomimetic Mannich macrocyclization. The modular construction of the carbon framework of these compounds is amenable to rapid structural diversification for the development of antibiotic and antitumor agents.

Bioinspired iterative synthesis of polyketides.

Diverse array of biopolymers and second metabolites (particularly polyketide natural products) has been manufactured in nature through an enzymatic iterative assembly of simple building blocks. Inspired by this strategy, molecules with inherent modularity can be efficiently synthesized by repeated succession of similar reaction sequences. This privileged strategy has been widely adopted in synthetic supramolecular chemistry.

Study on the total synthesis of velbanamine: Chemoselective dioxygenation of alkenes with PIFA via a stop-and-flow strategy.

A "stop-and-flow" strategy was developed for the chemoselective dioxygenation of alkenes with a PIFA-initiated cyclization. This method is conceived for the desymmetrization of seco-diene, and a series of substituted 5-hydroxymethyl-γ-lactones were constructed after hydrolysis. This strategy also differentiates terminally substituted alkenes and constitutes a potentially novel synthetic approach for the efficient synthesis toward velbanamine.

Chiral silver phosphate-catalyzed cycloisomeric kinetic resolution of α-allenic alcohols.

A kinetic resolution of α-allenic alcohols is realized through chiral silver phosphate-catalyzed cycloisomerization with high stereoselectivity (selectivity factor up to 189) and tolerance of a variety of functional groups. A mechanistic model is proposed to interpret the origin of the high stereoselectivity and broad substrate scope.