Organocatalytic enantioselective synthesis of 1,3,5-polyols by means of iterative asymmetric epoxidation: their application to the total synthesis of polyrhacitide A

We have developed a pragmatic route to the stereogenic skipped 1,3,5-polyols. The strategic transformation includes an organocatalytic enantioselective asymmetric epoxidation, which is either syn- or anti-selective as genesis of chirality and successive S_N2 opening reaction by an appropriate functionalized nucleophile, followed by hydroboration/oxidation to generate stereoisomers in good yield. The critical intermediate generated en route to this process is employed in the total synthesis of polyrhacitide A.     

Thirty-five years of synthetic studies directed towards the histrionicotoxin family of alkaloids

This article brings together for the first time reviews of all the synthetic attempts towards the spirocyclic histrionicotoxin alkaloids published since the discovery of the group in 1971. This covers 5 total syntheses of the fully unsaturated parent alkaloid HTX-283A, 7 total syntheses of perhydrohistrionicotoxin, 15 total syntheses of other members of this alkaloid family, 25 formal syntheses, and 19 partial syntheses involving the successful formation of the core azaspirocyclic structure but lacking advancement towards the target structure.     

A Morita-Baylis-Hillman adduct allows the diastereoselective synthesis of styryl lactones

We disclosed herein a diastereoselective approach for the total syntheses of (±)-Leiocarpin A and (±)-Goniodiol. These biologically active styryl lactones were obtained from a common intermediate, prepared in five steps and 40% overall yield, using a simple synthetic sequence starting from a Morita-Baylis-Hillman adduct. The total syntheses of these styryl lactones were accomplished in nine steps. This is the first report on the total synthesis of this class of natural products starting from Morita-Baylis-Hillman adduct.     

Total synthesis of infectopyrone,aplysiopsenes A–C,ent-aplysiopsene D,phomapyrones A and D, 8,9-dehydroxylarone,and nectriapyrone

The total synthesis of the 2-pyrone natural products nectriapyrone, aplysiopsenes A–C, ent-aplysiopsene D, phomapyrones A and D, and of 8,9-dehydroxylarone were achieved by Wittig olefination starting with vermopyrone. Infectopyrone was synthesized by Horner–Wadsworth–Emmons reaction starting with phomapyrone D. Racemic phomapyrone C methyl ether was obtained by hydrogenation of nectriapyrone. The total syntheses were achieved starting from commercially available 3,5-heptanedione and led to the desired natural products in 18–46% over 5–6 steps, whereupon all five-step syntheses were carried out with a single chromatographic workup. The total synthesis of infectopyrone, aplysiopsenes A–D, of phomapyrones A and D, and of 8,9-dehydroxylarone were achieved for the first time, giving unambiguous proof for the proposed structures of these natural products.     

Total syntheses of polyketide-derived bioactive natural products

Recent progress of total syntheses in our laboratory has been described along with our background and methodologies. The target bioactive polyketides are classified into three categories according to their structures: (i) lactone-fused polycyclic compounds [(+)-cochleamycin A, (+)-tubelactomicin A, and (-)-tetrodecamycin], (ii) aromatic compounds [(-)-tetracycline, (-)-BE-54238B, lymphostin, and (-)-lagunamycin], and (iii) acyclic polyketides [xanthocillin X dimethylether, (+)-trichostatin D, and (+)-actinopyrone A]. Features of the total syntheses are described. Original methodologies have been developed and applied to construct the inherent structures of the target molecules. Most syntheses cited herein are the first total syntheses, and the absolute structures of the target molecules have been determined.     

Synthetic studies towards pentacyclic quassinoids: total synthesis of unnatural (-)-14-epi-samaderine E and natural (-)-samaderine Y from (S)-(+)-carvone

First total syntheses of unnatural (-)-14-epi-samaderine E (5) and natural (-)-samaderine Y (2) were accomplished from (S)-(+)-carvone (6) in 18 and 21 steps, respectively. The syntheses are short, efficient (with an average yield of 80 % plus for each transformation), enantiospecific, and produce nine new chiral centers. The crucial points of the syntheses included a regioselective allylic oxidation on ring C, regio- and stereoselective reduction of ketone, a stereocontrolled epoxidation, an epoxymethano-bridge formation, a chemoselective Grignard reaction, an intramolecular Diels-Alder reaction, an intramolecular aldol addition, and a newly developed manganese(III)-catalyzed allylic oxidation on ring A.     

The first syntheses of 3-bromofascaplysin, 10-bromofascaplysin and 3,10-dibromofascaplysin—marine alkaloids from Fascaplysinopsis reticulata and Didemnum sp. by application of a simple and effective approach to the pyrido[1,2-a:3,4-b′]diindole system

A simple and practical approach for the synthesis of the marine sponge pigment fascaplysin was used for the total syntheses of its natural derivatives, the marine alkaloids 3-bromofascaplysin, 10-bromofascaplysin, and 3,10-dibromofascaplysin. The conditions of each step were revised, and as a result these compounds were produced by identical procedures with total yields of 40-43%.     

Recent progress toward synthesis of chlorosulfolipids: total synthesis and methodology

Chlorosulfolipids (CSLs) are an intriguing family of natural products featuring highly chlorinated linear hydrocarbon skeletons. Although CSLs were first isolated in 1962, chemical synthesis of CSLs was hampered because relevant methods for stereoselective construction of the polychlorinated motifs of CSLs were scarce. Since Carreira’s first total synthesis of the CSL mytilipin A in 2009, several groups, including our own, have reported total syntheses of CSLs. As a result of these total syntheses, important progress has been made in the development of reliable synthetic methods for stereoselective polychlorination. In this digest, we summarize the total syntheses of CSLs by focusing on synthetic methods for stereoselective polychlorination of the organic frameworks of CSLs.     

Brefeldin A全合成研究新进展

Brefeldin A(布雷菲德菌素甲)是一种天然抗生素, 最早发现于1958年, 许多种微生物中都能产生该化合物. 由于其有趣的结构和显著的抗真菌、抗病毒、抗肿瘤等生物活性, 该化合物很早就引起合成化学家们的注意. 到目前为止, 文献中有报道的全合成和表观合成已有30多种. 对近十年来的全合成及部分表观合成进行了综述, 对各路线的主要优缺点也进行了简要的分析. 一些类似物的合成也一并予以简介.     

First asymmetric total syntheses of (-)-subincanadines a and B, skeletally rearranged pentacyclic monoterpenoid indole alkaloids in aspidospermasubincanum

We achieved the first asymmetric total syntheses of novel Aspidosperma indole alkaloids, (-)-subincanadines A and B, which involve an intramolecular diastereoselective Pictet-Spengler cyclization and an intramolecular Nozaki-Hiyama-Kishi reaction as key steps in the total syntheses.     

A Configurational Switch Based on Iridium‐Catalyzed Allylic Cyclization: Application in Asymmetric Total Syntheses of Prosopis,Dendrobate, and Spruce Alkaloids

A method for the stereoselective synthesis of 2,6‐disubstituted piperidines has been developed that is based on the use of an intramolecular iridium‐catalyzed allylic substitution as a configurational switch. The procedure allows the preparation of 2‐vinylpiperidines with enantiomeric excesses (ee) of greater than 99 %. As applications, total syntheses of piperidine alkaloids have been elaborated, most often by using Ru‐catalyzed cross‐metatheses as a key step for introduction of a side chain. Asymmetric total syntheses of the prosopis alkaloids (+)‐prosopinine, (+)‐prosophylline, (+)‐prosopine, and of the dendrobate alkaloid (+)‐241D and its C6 epimer are described.     

Total syntheses of five indole alkaloids from the marine bryozoan Flustra foliacea

A general, efficient, and conceptually new approach to the total syntheses of marine-derived indole alkaloids, including (+/-)-flustramines A (1) and B (2), (+/-)-flustramides A (3) and B (4), and (+/-)-debromoflustramine B (5), is outlined. The key step in the syntheses involves the conjugated addition of an organomagnesium species derived from prenyl bromide to 2-hydroxyindolenines. Compounds 1, 2, and 5 have been synthesized in five steps with 23%, 17%, and 16% overall yield, respectively, whereas flustramides 3 and 4 have been synthesized in only four steps with 24% and 18% overall yield, respectively, on the basis of 2-hydroxyindolenines.     

One-pot total syntheses of natural products containing a THP-ring backbone: (±)-centrolobine and (±)-civet cat secretion

A one-pot strategy is devised and applied to the total syntheses of natural products with a THP-ring backbone. A special feature of this one-pot synthesis is the recyclability of the indium complex byproduct generated from the indium-mediated allylation reaction for concurrent catalysis in subsequent steps. Centrolobine and civet cat secretion are synthesized via this new method in overall yields of 58% and 23%, respectively.     

Total syntheses of ent-heliespirones A and C

Stereodivergent total syntheses of ent-heliespirone A and C were both completed in 11 vessels and ～24% combined overall yield (A + C). These syntheses employed an identical inverse demand Diels-Alder reaction between a surrogate for an extendedly conjugated γ-δ unsaturated ortho-quinone methide and L-lactic-acid-derived exocyclic enol ether. Novel reactions of special note include a diastereoselective reduction of a chroman spiroketal by combination of borontrifluoride etherate and triethyl silane, along with oxidative rupture of a chroman etherial ring into the corresponding p-quinone by argentic oxide (AgO). In addition, an unusual intramolecular etherification of a 3° alcohol caused by cerium ammonium nitrate was observed.     

Total synthesis of lansiumamides A and B and alatamide

The total syntheses of lansiumamide A, lansiumamide B and alatamide have been completed taking advantage of the dihalo-olefination of N-formylimides. The syntheses are convergent, flexible and allow for the generation of analogues not accessible through other routes.     

Palladium (II) catalyzed 5-endo epoxynitrile cyclizations: total syntheses of enokipodins A and B

New total syntheses of the cuparenic sesquiterpenes enokipodins A and B were accomplished. The key step involves a novel, cationic-controlled and palladium (II) improved, 5-endo cyclization of an α-aryl-δ-epoxynitrile. The cyclization occurs with unmatched regioselectivity and high stereoselectivity. The synthesis is completed in 5 steps achieving yields of 50% for enokipodin A and 55% for enokipodin B.     

High-throughput purification of combinatorial libraries II: Automated separation of single diastereomers from a 4-amido-pyrrolidone library containing intentional diastereomer pairs

A 4-amido-pyrrolidone library that was intentionally synthesized as pairs of diastereomers was produced by solution-phase parallel syntheses and purified by an automated high-throughput purification system. A total of 2592 4-amido-pyrrolidinones were ultimately isolated as single diastereomers from a matrix of 1920 syntheses. After the four-step synthesis and HPLC purification, the average yield of a single diastereomer was 36.6%. The average chemical purity was >90%, and the average diastereomeric purity was >87%. The choice of chiral amines used to make amides with heterocyclic acid chlorides had a dramatic effect on success. Analysis of the relationship between amines used for synthesis and the diastereomeric separation showed that amides made from chiral 1,2-amino alcohols gave superior separation to amides from chiral morpholines. The presence of a hydrogen bond donor on the amide side chain seems to be required for a better diastereomeric separation.     

2种苯并吡喃类查尔酮天然产物的全合成

2种苯并吡喃类查尔酮天然产物的全合成;全合成;苯并吡喃类查尔酮;三羟基苯乙酮;柠檬醛;苯甲醛     

Enantioselective total syntheses of welwitindolinone A and fischerindoles I and G

The first total syntheses of welwitindolinone A and the most complex members of the fischerindole family, fischerindoles I and G, are reported. Highlights of these short, protecting-group-free syntheses include the application of the recently developed direct indole-carbonyl coupling, a simple approach for installing the quaternary center with neighboring chlorine atom, a regioselective dehydrogenation/dehydration cascade to access fischerindole I, and a remarkably facile oxidative ring contraction to construct welwitindolinone A. An alternative biogenetic hypothesis, whose accuracy is suggested by the success of the current syntheses, is also put forth for this alkaloid family.     

Asymmetric annulation toward pyrrolopiperazinones: concise enantioselective syntheses of pyrrole alkaloid natural products

A novel Pd-catalyzed asymmetric annulation between 5-bromopyrrole-2-carboxylate esters and vinyl aziridines has been developed to efficiently construct pyrrolopiperazinones, which can serve as key intermediates in the enantioselective syntheses of pyrrole alkaloid natural products. In this paper, the total synthesis of (-)-longamide B in five steps and the first total syntheses of agesamides A and B in six steps from 6 and 7 are reported.