Enantioselective total syntheses of (+)- and (−)-ottelione A and (+)- and (−)-ottelione B. Absolute configuration of the novel, biologically active natural products

Following our recent total synthesis of the biologically potent natural products otteliones A and B in racemic form, we have now accomplished the total synthesis of both the enantiomers of otteliones A and B through an enantiodivergent strategy emanating from the readily available Diels-Alder adduct of cyclopentadiene and p-benzoquinone. These endeavors have led to the elucidation of the absolute configuration of naturally occurring otteliones A and B.     

First total synthesis of yanuthones: novel farnesylated epoxycyclohexenoid marine natural products

The total synthesis of the recently isolated marine natural products of mixed biosynthetic origin, yanuthones A, B, C and 22-deacylyanuthone A, has been accomplished following a short regio- and stereocontrolled approach involving the key intermediacy of 2-farnesyl-p-benzoquinone.     

First total synthesis of rhuscholide A,glabralide B and denudalide

The first total synthesis of rhuscholide A, a benzofuran lactone possessing anti-HIV-1 activity, had been accomplished in 14 linear steps with 10.6% overall yield. In this synthesis, base-mediated phenol ortho-alkylation and piperidine promoted aldol condensation were exploited as key steps. The synthesis was flexible and allowed for the convenient preparation of two analogous natural products glabralide B and denudalide.     

Total synthesis of the indole alkaloids henrycinol A and B

The total synthesis of new indole alkaloids henrycinol A and B were accomplished starting from l-tryptophan methyl ester. The key step is a stereochemically flexible Pictet–Spengler reaction governed by the presence or absence of an N-allyl group in the tryptophan precursor. The natural products henrycinol A and B were synthesized in good overall yield in eight and nine steps, respectively.     

Total synthesis of farylhydrazones A and B

Herein we report a concise total synthesis of farylhydrazones A and B, naturally occurring phenylhydrazones recently isolated from cultures of the Cordyceps-colonizing fungus Isaria farinosa, completed in six and five steps respectively starting from 2-nitrobenzoic acid. The synthesis is completely scalable, and highly convergent—making it adaptable for the preparation of analogues and investigation into the biological activity of these unique natural products.     

First total synthesis of the β-carboline alkaloids trigonostemine A,trigonostemine B and a new synthesis of pityriacitrin and hyrtiosulawesine

The total synthesis of four natural products, trigonostemine A, trigonostemine B, pityriacitrin, and hyrtiosulawesine was accomplished. The key intermediates, variously substituted 1-formyl-β-carbolines, were prepared in five steps via a novel synthetic approach using readily available starting materials. These formyl derivatives were then further transformed, providing a general route for the synthesis of the four title alkaloids. The method reported herein represents the first total synthesis of the two trigonostemines and a new pathway to pityriacitrin and hyrtiosulawesine.     

Total synthesis of macrocyclic glycosides, clemochinenosides A and B, and berchemolide, by fluorous mixture synthesis

The total synthesis of clemochinenoside A and the first total syntheses of clemochinenoside B and berchemolide were achieved simultaneously via macrocyclization of 4-O-(4-O-^F13benzyl-β-d-glucopyranosyl)syringic acid with 4-O-(4-O-^F17benzyl-β-d-glucopyranosyl)vanillic acid by a fluorous mixture synthetic method. The spectroscopic data of the synthetic products were identical with those of the natural products, although the optical rotation of clemochinenoside A differed from the published values in sign and magnitude.     

Enantioselective total synthesis of (R)-strongylodiols A and B

We describe an expeditious enantioselective total synthesis of the acetylenic marine natural products (R)-strongylodiols A and B. Central to the strategy is the use of Zn(OTf)₂, amine base, and N-methyl ephedrine to mediate the direct addition of a 1,3-diyne to two long-chain aliphatic aldehydes in useful selectivities and yields.     

Total synthesis of natural fregenedadiol and its diacetate,rearranged labdanes with aromatized B ring

Labdane based natural products are most abundant and widely distributed in nature with many compounds exhibiting exceptional biological properties. Fregenedadiol is a bicyclic diterpene isolated from Halimium viscosum and represents a new carbon skeleton fregenedane with its B ring aromatized. Here, we report a total synthesis of this interesting natural product using one-pot Diels-Alder/aromatization sequence and selective hydrogenolysis as key steps.     

Total synthesis and stereochemistry assignment of 15-membered peptide alkaloids abyssenine B and mucronine E

The total synthesis of 15-membered peptide alkaloids abyssenine B and mucronine E was accomplished via olefination of phenylalanine-embodied aldehydes followed by CuI/N,N-dimethylglycine-catalyzed coupling of vinyl iodides with amides and FDPP-mediated macrocyclization in the key steps. From the total synthesis the stereochemistry of these two natural products was tentatively assigned to be S,S,S.     

Total synthesis and absolute configuration of otteliones A and B, novel and potent antitumor agents from a freshwater plant

[reaction: see text] The first enantioselective total synthesis of otteliones A and B, biologically important and structurally novel natural products, has been successfully achieved. This total synthesis fully confirms the absolute configuration of these natural products.     

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.     

Asymmetric synthesis of cytotoxic sponge metabolites R-strongylodiols A and B

The asymmetric synthesis of the marine sponge natural products, R-strongylodiols A 1 and B 2 using a minimum protection strategy is described. The chirality of the natural products was introduced via the Noyori asymmetric reduction of ynones.     

Total synthesis and structural validation of cyclodepsipeptides solonamide A and B

Microorganisms are an attractive source of new natural products with antimicrobial properties, and the marine environment constitutes a prolific resource of bioactive microorganisms. During a global research expedition (Galathea III), two depsipeptides, solonamide A and solonamide B, were isolated from the marine bacterium Photobacterium halotolerance and were found to inhibit virulence gene expression in the serious human pathogen, Staphylococcus aureus. They act by interfering with the agr quorum sensing system and show resemblance to the endogenous S. aureus quorum sensing peptide, autoinducing peptide I (AIP-I). To enable more comprehensive studies, we embarked on the chemical synthesis of solonamides A and B. The key synthetic steps were formation of the (R)-β-hydroxy-fatty-acids by stereo-selective aldol reactions and a cyclative macrolactamization, which proceeded under highly dilute conditions. Thus, the first total syntheses of the solonamides corroborated the originally assigned structures, and by changing the stereochemistry of the auxiliary in the aldol steps we gained access to the natural products as well as their β³-epimers.     

Formal synthesis of schulzeines B and C

A formal synthesis of schulzeines B and C, marine natural products with inhibitory effect against α-glucosidase, has been achieved. The key reactions of the synthesis are N-acyliminium ion cyclization, Sharpless asymmetric dihydroxylation, olefin cross metathesis, and asymmetric allylboration.     

Total Syntheses of Linear Polythiazole/Oxazole Plantazolicin A and Its Biosynthetic Precursor Plantazolicin B

Plantazolicin A, a linear decacyclic natural product, exhibits desirable selective activity against the causative agent of anthrax toxicity. The total synthesis of plantazolicin A and its biosynthetic precursor plantazolicin B was successfully achieved by an efficient, unified, and highly convergent route featuring dicyclizations to form 2,4‐concatenated oxazoles and the mild synthesis of thiazoles from natural amino acids. This report represents the first synthesis of plantazolicin B and includes the first complete characterization data for both natural products.     

Total synthesis of natural (+)-sesbanimide a and (-)-sesbanimide b

The first total synthesis of natural (+)-sesbanimide A (1) and (-)-sesbanimide B (2), potent antitumor alkaloids isolated from the seeds of the leguminous plant, Sesbania drummondii, has been accomplished starting from D-(+)-xylose. This total synthesis involves efficient construction of the optically active AB-ring system from D-(+)-xylose, introduction of the C₅-unit into the AB-ring system in a form of exo-methylene-γ-lactone, and elaboration of the labile C-ring system at the last stage of the synthesis. The absolute configurations of natural 1 and 2 could be obviously established by our total synthesis.     

A closer look on various synthetic routes to Callystatin A: a cytotoxic marine sponge polyketide

Callystatin A, a polyketide marine natural product, has been known since 1997 after its isolation from the sponge Callyspongia truncata by Kobayashi et al. It belongs to the leptomcyin family of natural products with a highly conjugated and stereodefined skeleton. The challenging structural topographies and remarkable anti-proliferative properties of (?)-Callystatin A stimulated many researchers to pursue the total synthesis of this marine polyketide. This review is exclusively focused on the research undertaken towards the concise, asymmetric total synthesis of Callystatin A over the last two decades. The various target oriented synthetic pathways are discussed in a chronological order to give a comprehensive overview.     

Isolation and total synthesis of two novel metabolites from the fissurellid mollusc Scutus antipodes

There is almost no information on natural products from gastropods in the order Vetigastropoda and nothing at all for the superfamily Fissurellidae (keyhole and slit limpets), which are only partially protected from predation by their shell. Extraction of the Australian fissurellid Scutus antipodes yielded two new compounds, scutinin A [d-sorbityl hexakis(p-hydroxybenzoate)] and scutinin B [2-ethylhexane-1,3-bis(p-hydroxybenzoate)] that were identified by spectroscopic analysis and their structures confirmed by total synthesis. The compounds were found to have antimicrobial activity but no fish antifeedant activity.     

Total synthesis of (−)-Englerin A

A novel and efficient total synthesis of Englerin A is reported. The synthesis featured an intramolecular olefin metathesis ring closure reaction and a highly stereoselective oxygen bridge formation induced by an iodonium ion. This strategy can be used for the synthesis of natural products Englerin A and Englerin B and can provide flexibility in the preparation of various 9-substituted analogues of Englerin A for further structure–activity relationship studies.