Synthesis Of Marine Natural Product Research Articles

A simple and efficient pathway for the total synthesis of marine natural products: bengamide E and 5-epi-bengamide E.

Total synthesis of the marine natural product bengamide E and 5-epi-bengamide E has been accomplished using two routes: (i) via a polyhydroxy acid precursor involving a total of 16 steps with an overall yield of 17.0% and (ii) via a cyclic lactone precursor with a total of 12 steps and overall 23.0% yield. The key steps involve (1) regioselective p-methoxybenzylidine ring opening, (2) a stereoselective Grignard reaction and (3) olefin cross-metathesis. The total synthesis could provide significant quantities of bengamide E and 5-epi-bengamide E as all the reaction processes were very efficient and the raw materials were inexpensive and highly abundant. The protocol has an advantage over previously reported methods as it provides ready access to the C-5 hydroxy group for further modification and its future structure-activity relationship studies for anti-tumor activity.

Total Synthesis of Marine Natural Products (+)-Strongylin A and Corallidictyal D by Regio- and Stereoselective Cyclization of Alkenyl Benzenes.

An expeditious access to marine natural products (+)-strongylin A and corallidictyal D is described. A TFA/Et3SiH-induced reductive isomerization of enols I to alkenyl benzenes II followed by a selectivity-controlled cyclization in the presence of HCl and BF3·Et2O affords benzofuran III and benzopyran IV, respectively. The applicability of this HCl-induced cyclization is showcased by a regio- and stereoselective synthesis of corallidictyal D, while BF3·Et2O-promoted cyclization posterior to rearrangement of an alkenyl benzene provides a regioselectively different benzopyran, (+)-strongylin A.

Enantioselective total syntheses of marine natural products (+)-cylindricines C, D, E and their diastereomers

On the basis of the amide strategy, we have achieved the concise enantioselective total synthesis of (+)-cylindricines D, C, and E, and their 2-epimers in seven, eight, and nine steps, respectively.

Construction of N-Heterocycles Fused with a Highly Substituted Benzene Ring by a Benzyne-Mediated Cyclization/Functionalization Cascade Reaction and Its Application to the Total Synthesis of Marine Natural Products.

This account summarizes the development of a benzyne-mediated cyclization/functionalization protocol for the versatile construction of highly substituted benzene derivatives fused with an N-heterocyclic ring such as indolines, indoles, and related nitrogen-containing heterocycles. The protocol comprises sequential reactions initiated by generating a benzyne species and subsequent cyclization via addition of magnesium amide to the benzyne, followed by trapping of the resultant magnesium compound in situ with various electrophiles. The substituent scope was expanded by conducting a transmetalation on a copper species to introduce alkyl, aryl, and alkenyl substituents. The utility of the sequential reaction was demonstrated in the synthesis of a carbazole natural product (heptaphylline), pyrrolo[4,3,2-de]quinoline alkaloids (batzellines), and pyrrolo[2,3-c]carbazole alkaloids (dictyodendrines).

Total Synthesis and Anti-Inflammatory Bioactivity of (-)-Majusculoic Acid and Its Derivatives.

The first total synthesis of marine natural product, (−)-majusculoic acid (1) and its seven analogs (9–15), was accomplished in three to ten steps with a yield of 3% to 28%. The strategy featured the application of the conformational controlled establishment of the trans-cyclopropane and stereochemical controlled bromo-olefination or olefination by Horner–Wadsworth–Emmons (HWE) reaction. The potential anti-inflammatory activity of the eight compounds (1 and 9–15) was evaluated by determining the nitric oxide (NO) production in the lipopolysaccharide (LPS)-induced mouse macrophages RAW264.7. (−)-Majusculoic acid (1), methyl majusculoate (9), and (1R,2R)-2-((3E,5Z)-6-bromonona-3,5-dien-1-yl)cyclopropane-1-carboxylic acid (12) showed significant effect with inhibition rates of 33.68%, 35.75%, and 43.01%, respectively. Moreover, they did not show cytotoxicity against RAW264.7 cells, indicating that they might be potential anti-inflammatory agents.

Developing a Methodology for Catalytic Asymmetric Crotylation of Aldehydes

AbstractAsymmetric crotylation has firmly earned a place among the set of valuable synthetic tools for stereoselective construction of carbon skeletons. For a long time the field was heavily dominated by reagents bearing stoichiometric chiral auxiliaries, but now catalytic methods are gradually taking center stage, and the area continues to develop rapidly. This account focuses primarily on preformed organometallic reagents based on silicon and, to some extent, boron. It narrates our endeavors to design new and efficient chiral Lewis base catalysts for the asymmetric addition of crotyl(trichloro)silanes to aldehydes. It also covers the development of a novel protocol for kinetic resolution of racemic secondary allylboronates to give enantio- and diastereomerically enriched linear homoallylic alcohols. As a separate topic, cross-crotylation of aldehydes by using enantiopure branched homoallylic alcohols as a source of crotyl groups is discussed. Finally, the synthetic credentials of the developed methodology are illustrated by total syntheses of marine natural products, in which crotylation plays a key role in setting up stereogenic centers.1 Introduction2 Pyridine N-Oxides as Lewis Base Catalysts3 Bipyridine N,N′-Dioxides as Lewis Base Catalysts4 Chiral Allylating Reagents5 Synthetic Applications6 Concluding Remarks

Reaction Development Utilizing the Features of Chemical Elements and Synthesis of Marine Natural Products

Marine natural products and biologically active compounds often contain cyclic ether units. Thus, regio- and stereoselective construction of these structures has long been a topic of interest in organic synthesis. This review summarizes new synthetic approaches to polycyclic ether natural products utilizing the features of chemical elements.

Toward the Synthesis of Phormidolides.

A convergent and stereoselective approach for the synthesis of marine natural product (MNP) phormidolide D (PM D) is proposed. Two main disconnections divided PM D in three molecular fragments: the macrocyclic core 4, the stapling iodoalkene 9 corresponding to the central part of PMs, and the east fragment 5 that includes the unusual bromo-methoxy-diene moiety and a tetradecanoic acid ended with a (E)-dichloro-ene functionality. Procedures for the preparation of compounds 5, 9, and the never-reported fatty acids 7 and 8, present in PMs C and D, respectively, have been afforded with good yields and high degree of stereoselectivity. The absolute configuration of all of the generated stereocenters has been established. The reaction to link iodoalkene 9 and formylmacrolactone 4, using the Nozaki–Hiyama–Takai–Kishi coupling, gave an advanced synthetic intermediate with total stereocontrol. Finally, a deeper study of protecting groups and reaction conditions for the last step of the synthesis is needed. All the information gathered in this publication will be of great value to continue performing synthetic studies for the preparation of these NPs. The versatility and the presence of a common polyol chain in oscillariolide and PMs A–C would allow applying the same retrosynthesis for the synthesis of the mentioned MNP.

Total Synthesis of Marine Natural Products: Cephalosporolides

AbstractMarine‐derived species, in particular, fungi, algae, sponges, and coelenterates are fertile grounds for the discovery of biologically and pharmacologically potent compounds. These molecules are structurally unique and possess a wide range of pharmacological activities. The rigid spiroacetal framework, that is, tetrahydro‐spirofurofuranones is present in cephalosporolides E, F, H, and I, while the macrolactone structure is exemplified by cephalosporolides B, C, D, G, and J. These marine‐derived molecular architectures are appealing to the synthetic community for their stereoselective synthesis. The present review represents a comprehensive overview of all the reported syntheses of these marine‐derived molecules.

ChemInform Abstract: Marine Natural Products

AbstractReview: isolation, biological activities, source organisms, biosynthetic studies, and irst syntheses of marine natural products published in 2014; 938 refs.

ChemInform Abstract: Recent Advances in the Synthesis of 2‐Pyrones

AbstractReview: and application to the synthesis of marine natural products; 96 refs.

Synthesis of marine natural products that contain a CIS-enamide fragment

Indolic enamides are a rare class of marine natural products that have demonstrated a broad range of biological activities, including cytotoxicity and antibacterial activities. Examples of this class of compounds include coscinamides A-C, isolated from the marine sponge Coscinoderma sp., and chondriamides A-C, isolated from the red alga Chondria sp. and Chondria atropurpurea. While a number of synthetic routes targeting the trans-enamide moiety have been reported, little is known regarding the stereoselective synthesis of the indolic cis-enamide fragment. We have made use of a recently reported alkyne hydroamidation methodology to develop a general strategy for the synthesis of cis-enamide containing natural products. This strategy, its strengths and weaknesses, as well as approaches to the synthesis of specific natural products will be presented.

Marine natural products synthesis as a driving force for chemical and biological discovery

Marine natural products synthesis as a driving force for chemical and biological discovery

Recent advances in the synthesis of 2-pyrones.

The present review summarizes the recent progresses in the synthesis of 2-pyrones and the application to the synthesis of marine natural products. Especially, much attention was placed on the transition metal catalyzed synthetic methodologies in this review.

Synthesis of marine natural product (-)-pericosine E.

The first synthesis of (-)-pericosine E (6), a metabolite of the Periconia byssoides OUPS-N133 isolated originally from the sea hare Aplysia kurodai, has been achieved. Efficient and regioselective synthetic procedures for the synthesis of key intermediates, anti- and syn-epoxides 9 and 10, were developed using an anti-epoxidation of diene 12 with TFDO and a bromohydrination of 12 with NBS in CH(3)CN/H(2)O (2:3), respectively. In addition, comparison of the specific optical rotations between synthetic 6 and natural 6 elucidated that the naturally preferred enantiomer of pericosine E had the same absolute configuration as (-)-6 synthesized from chlorohydrin (-)-8 and anti-epoxide (+)-9.

ChemInform Abstract: Palladium‐Mediated Total Synthesis of Bioactive Natural Products

AbstractReview: ca. 300 refs.

Palladium-Mediated Total Synthesis of Bioactive Natural Products

The search for efficient synthetic procedures for natural products, drugs, and materials with economical and ecological advantages is an important area of current interst in synthetic organic chemistry. We have made an attempt to summarize the progress made in this area since 2005. This article describes the syntheses of several natural products and drugs that employ multiple palladium-catalyzed processes in either a sequential or a domino fashion. 1 Introduction 2 Palladium-Mediated Synthesis of Alkaloids 2.1 Indole Alkaloids 2.2 Carbazole Alkaloids 2.3 Quinoline and Isoquinoline Alkaloids 2.4 Pyrrole and Pyridine Alkaloids 2.5 Pyrrolizidine and Indolizidine Alkaloids 2.6 Imidazole and Guanidine Alkaloids 2.7 Other Alkaloids 3 Palladium-Mediated Synthesis of Natural Products Containing a Sugar Moiety 4 Palladium-Mediated Synthesis of Marine Natural Products 5 Palladium-Mediated Synthesis of Amino Acids and Peptides 6 Palladium-Mediated Synthesis of Terpenoids 7 Miscellaneous Natural Products 8 Conclusion

Marine natural products: synthetic aspects

Covering: January to December 2010. Previous review: Nat. Prod. Rep., 2011, 28, 269. An overview of marine natural products synthesis during 2010 is provided. As with earlier installments in 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.

The first total synthesis and biological evaluation of marine natural products ma’edamines A and B

We have developed the first total syntheses of marine natural products ma’edamines A (18) and B (20). Structurally, they contain a pyrazine-2-(1H)-one core and were screened for antiproliferative activity on several cancer cell lines. Out of the six cell lines tested, ma’edamines A and B showed significant cytotoxicity against human colon cancer line COLO 205 (IC50 7.9 and 10.3μM, respectively), breast cancer cell line MCF-7 (IC50: 6.9 and 10.5μM, respectively) and human lung adenocarcinoma cell line A549 (IC50: 12.2 and 15.4μM, respectively). The apoptotic effect of ma’edamines was confirmed by comet assay. Hence ma’edamines are likely to be useful as leads for development of a new class of anti-cancer agents.

ChemInform Abstract: Marine Natural Products: Synthetic Aspects

AbstractReview: ca. 150 refs.