The bloom of natural product chemistry in China

正Natural product chemistry is an important area across chemistry,biology,and pharmaceutical sciences.The discovery of natural products through isolation and structural elucidation expands the chemical space of biologically active molecules in an unparallel fashion;numerous medicinally relevant compounds arise from natural product scaffolds.The chemical synthesis of natural products advances the development of organic chemistry from the theoretical,     

Linking chemistry and genetics in the growing cyanobactin natural products family

Ribosomal peptide natural products are ubiquitous, yet relatively few tools exist to predict structures and clone new pathways. Cyanobactin ribosomal peptides are found in ~30% of all cyanobacteria, but the connection between gene sequence and structure was not defined, limiting the rapid identification of new compounds and pathways. Here, we report discovery of four orphan cyanobactin gene clusters by genome mining and an additional pathway by targeted cloning, which represented a tyrosine O-prenylating biosynthetic pathway. Genome mining enabled discovery of five cyanobactins, including peptide natural products from Spirulina supplements. A phylogenetic model defined four cyanobactin genotypes, which explain the synthesis of multiple cyanobactin structural classes and help direct pathway cloning and structure prediction efforts. These strategies were applied to DNA isolated from a mixed cyanobacterial bloom containing cyanobactins.     

Fine synthetic nucleoside chemistry based on nucleoside natural products synthesis

Synthetic nucleoside chemistry based on nucleoside natural products synthesis were described. First, a samarium diiodide (SmI 2)-promoted aldol reaction with the use of alpha-phenylthioketone as an enolate was developed. The characteristics of this reaction are that the enolate can be regioselectively generated and the aldol reaction proceeds under near neutral condition. This reaction is proved to be a powerful reaction for the synthesis of complex nucleoside natural products, and herbicidin B and fully protected tunicaminyluracil, which were undecose nucleoside natural products, were synthesized. Next, the synthetic methodology of the caprazamycins, which are promising antibacterial nucleoside natural products, was also developed by the strategy including beta-selective ribosylation without using a neighboring group participation. Our synthetic route provided a range of key analogues with partial structures to define the pharmacophore. Simplification of the caprazamycins was further pursued to develop diketopiperazine analogs.     

Combinatorial chemistry of natural products: Solid phase synthesis of D- and L-cycloserine derivatives

An efficient methodology for a solid phase synthesis of D- and L-cycloserine derivatives is described. Fmoc-D-cycloserine 4 and its L-enantiomer 5 prepared by a selective amine acylation of bis-silylated parent compounds are immobilized on Sasrin or 2-chlorotrityl linker resins using Mitsunobu-type reaction or direct tritylation, respectively. The resulting Fmoc-cycloserine resins 7, 10, and 11 are deprotected with piperidine in DMF or DCM to generate immobilized cycloserine reagents with a primary amino group exposed for various synthetic transformations. An example of the parallel D-cycloserine library synthesis on a reaction plate is described.     

Highlights of marine natural products chemistry (1972-1999)

Marine Natural Products Chemistry is essentially a child of the 1970's that developed rapidly during the 1980's and matured in the last decade. With a few notable exceptions, it is difficult to select individual papers that significantly impacted the field. However, marine natural products chemistry has often influenced other fields and that aspect is the focus of this review. It is clear that the early directions taken by marine natural products chemists drew as much from the examples provided by insect chemical ecology as from the longer history of phytochemistry. By 1975 there were already three parallel tracks in marine natural products chemistry: marine toxins, marine biomedicinals and marine chemical ecology. It is the integration of the three fields of study that has given marine natural products chemistry its unique character and vigour.     

Property distributions: differences between drugs,natural products,and molecules from combinatorial chemistry

The differences between three different compound classes, natural products, molecules from combinatorial synthesis, and drug molecules, were investigated. The major structural differences between natural and combinatorial compounds originate mainly from properties introduced to make combinatorial synthesis more efficient. These include the number of chiral centers, the prevalence of aromatic rings, the introduction of complex ring systems, and the degree of the saturation of the molecule as well as the number and ratios of different heteroatoms. As drug molecules derive from both natural and synthetic sources, they cover a joint area in property space of natural and combinatorial compounds. A PCA-based scheme is presented that differentiates the three classes of compounds. It is suggested that by mimicking certain distribution properties of natural compounds, combinatorial products might be made that are substantially more diverse and have greater biological relevance.     

Molecular biological access to the chemistry of unknown soil microbes: a new frontier for natural products

Cultured soil microorganisms have provided a rich source of natural-product chemistry. Because only a tiny fraction of soil microbes from soil are readily cultured, soil might be the greatest untapped resource for novel chemistry. The concept of cloning the metagenome to access the collective genomes and the biosynthetic machinery of soil microflora is explored here.     

Natural products in combinatorial chemistry: an andrographolide-based library

The generation of a natural-product-based library starting from andrographolide is described. Utilizing andrographolide itself in parallel solution-phase synthesis leads to a 360-membered library. The initial transformation of the starting material via ozonolysis is followed by the conversion into a suitable template by introduction of a thiazole moiety. Subsequent decoration at two points of diversity yields the desired natural product derivatives. The selection of actually synthesized compounds is based on a virtually generated library and the assessment of its members with respect to physicochemical parameters, thus ensuring pharmacological relevance of the compounds.     

The chemistry of marine furanocembranoids, pseudopteranes, gersolanes, and related natural products

An overview of the chemistry and biology of the diterpene natural products known as the furanocembranoids, pseudopteranes, and gersolanes is provided; 85 references are cited.     

Recent progress on the total synthesis of natural products in China

An overview of natural products synthesis in Mainland China during the past 10 years is provided. This review only emphasizes the first total synthesis of molecules of contemporary interest and syntheses that helped to correct structures. In addition, some significant results on the novel synthesis and structure-activity relationship (SAR) studies of several natural products are introduced.     

Marine natural products: synthetic aspects

An overview of marine natural products synthesis during 2003 is provided. The emphasis on total syntheses of molecules of contemporary interest, new total syntheses, and syntheses that have resulted in structure conformation or stereochemical assignments.     

Marine natural products: synthetic aspects

An overview of marine natural products synthesis during 2004 is provided. As with the previous installment of this series, the emphasis is on total syntheses of molecules of contemporary interest, new total syntheses, and syntheses that have resulted in structure confirmation or stereochemical assignments.