Asymmetric synthesis and biosynthetic implications of (+)-fusarisetin A

Starting from equisetin, the asymmetric synthesis of (+)-fusarisetin?A has been accomplished in a one-pot transformation including a biomimetic oxidation and an intramolecular Diels-Alder/Roskamp reaction. Peroxyfusarisetin is proposed as a plausible biosynthetic intermediate based on studies of the oxidation of equisetin.     

Nature-inspired total synthesis of (-)-fusarisetin A

A concise, protecting group-free total synthesis of (-)-fusarisetin A (1) was efficiently achieved in nine steps from commercially available (S)-(-)-citronellal. The synthetic approach was inspired by our proposed biosynthesis of 1. Key transformations of our strategy include a facile construction of the decalin moiety that is produced via a stereoselective IMDA reaction and a one-pot TEMPO-induced radical cyclization/aminolysis that forms the C ring of 1. Our route is amenable to analogue synthesis for biological evaluation.     

Wallichanol类天然产物ABC环系合成研究

Wallichanol是一类具有独特桥环结构的二萜天然产物.以2-甲基-1,3-环己二酮作为起始原料,通过高立体选择性的Diels-Alder反应和金催化的炔烃碳环化反应构建Wallichanol的ABC三环核心骨架,共七步路线,总收率为42%.该合成工作为Wallichanol类天然产物全合成奠定了研究基础.     

Total synthesis of (+)-frondosin A. Application of the Ru-catalyzed [5+2] cycloaddition

The first total synthesis of (+)-frondosin A was accomplished in 19 longest linear and 21 total steps from commercially available materials. The key features of the synthesis include a Ru-catalyzed [5+2] cycloaddition, a Claisen rearrangement, and a ring expansion to construct the core of the frondosin A in a diastereoselective and regioselective fashion. This is the first application of a Ru-catalyzed [5+2] cycloaddition in the total synthesis of a natural product. Through this synthesis, the absolute configuration of (+)-frondosin A was established.     

Total Synthesis and Biological Evaluation of the Glycosylated Macrocyclic Antibiotic Mangrolide A

The macrocyclic antibiotic mangrolide A has been described to exhibit potent activity against a number of clinically important Gram‐negative pathogens. Reported is the first enantioselective total synthesis of mangrolide A and derivatives. Salient features of this synthesis include a highly convergent macrocycle preparation, stereoselective synthesis of the disaccharide moiety, and two β‐selective glycosylations. The synthesis of mangrolide A and its analogues enabled the re‐examination of its activity against bacterial pathogens, and only minimal activity was observed.     

Enantioselective synthesis of saframycin A and evaluation of antitumor activity relative to ecteinascidin/saframycin hybrids

[formula: see text] A short synthesis of saframycin A is described which begins with a readily available intermediate previously utilized for the total synthesis of ecteinascidin 743. A key step in this synthesis is the use of 1-fluoro-3,5-dichloropyridinium triflate to oxidize a phenolic ring to a 1,4-benzoquinone unit while simultaneously cleaving a methoxymethyl ether of a different phenolic ring to the corresponding phenol (4-->5). The common intermediate (2) for the synthesis of saframycin A (1) and ecteinascidin 743 also allowed the synthesis of two hybrids of these structures (6 and 7). Whole cell bioassays for antitumor activity using lung, colon, melanoma, and prostate-derived tumor cell lines allowed a clear correlation of structure with biological activity in this series.     

Concise total synthesis of (-)-spongotine A

The first asymmetric total synthesis of spongotine A is described. The oxidative synthesis of the imidazoline/ketone unit from keto aldehyde and diamine is a key step in this synthesis. The absolute stereochemistry of the asymmetric center of natural spongotine A is revealed as the (S)-configuration.     

Total synthesis of natural (−)- and unnatural (+)-Melearoride A

This communication details the first total synthesis of the 13-membered macrolide, (?)-Melearoride A, as well as unnatural (+)-Melearoride A. The synthesis features a concise 13 step synthesis (11 steps longest linear sequence) that offers flexible stereo-control and multiple opportunities for unnatural analog synthesis to delve into antifungal SAR. The route features a cuprate addition, an Evans asymmetric alkylation, and a ring-closing metathesis (RCM) to close the 13-membered macrocyclic core.     

A metalation strategy for the construction of functionalized naphthalenes: the first synthesis of guieranone A

The first synthesis of the natural product guieranone A is described, demonstrating a one-pot procedure for the synthesis of protected-1,3,6,8-tetraoxygenated naphthalenes and a subsequent directed metalation synthesis of 2-keto naphthalenes.     

Enantioselective synthesis of the C10-C20 fragment of fusicoccin A

A synthesis of the fully protected C-ring fragment of the tricyclic diterpene fusicoccin A is reported. The desired cyclopentenyl halides 5a,b are obtained in a total of nine steps. Key transformations of the synthesis sequence are a nonconventional Cr-catalyzed allylic oxidation of a protected intermediate cylcopentenone, a diastereoselective addition of a propenyl Grignard/CeCl(3) reagent to the unmasked cyclopentenone, and an asymmetric hydroboration of the isopropenyl substituent. The protected and suitably functionalized C-ring fragment paves the way to explore further the total synthesis of fusicoccin A.     

Total synthesis of bafilomycin A1

A convergent synthesis of bafilomycin A(1), a potent inhibitor of V-type ATPases, is presented. The synthesis relies on the zinc triflate mediated diastereoselective addition of a complex enyne to a sensitive aldehyde as the key fragment coupling. A ruthenium-catalyzed trans-reduction of the resulting propargylic enyne efficiently installs the required C10-C13 trans,trans-diene subunit, implementing an alternative strategy to traditional palladium-catalyzed cross-coupling strategies. A highly selective oxidation of a secondary hydroxyl group in a triol sets the stage for the completion of the synthesis.     

Regioselective preparation of 2-substituted 3,4-diaryl pyrroles: a concise total synthesis of ningalin B

Methylisocyanoacetate undergoes a 2 + 3 cycloaddition with alpha,beta-unsaturated nitriles to provide a regioselective synthesis of 2-substituted 3,4-diaryl pyrroles. The ease of preparation of alpha,beta-unsaturated nitriles allows the rapid synthesis of pyrroles with varied substituents. Using this method, a key intermediate (1) for the synthesis of the marine natural products lukianol A, lamellarin O, and lamellarin Q was prepared in two steps. A total synthesis of ningalin B (11) was also accomplished utilizing this methodology.     

A total synthesis of millingtonine A

A total synthesis of millingtonine A, a diglycosylated alkaloid, has been accomplished. Millingtonine A possesses a unique racemic tricyclic core structure not known from any other natural or synthetic source until now. The synthesis features a key bond-forming radical Ueno-Stork cyclization to form the heterocyclic core.     

Concise total synthesis of (+)-brefeldin A: a combined beta-lactone/cross-metathesis-based strategy

[reaction: see text] A highly convergent total synthesis of (+)-brefeldin A that relies on a diastereoselective, beta-lactone-based cyclopentane synthesis combined with complex cross-metathesis reactions is described. The utility of beta-lactones for natural product synthesis and the versatility of cross-metathesis in this context were demonstrated, including the tolerance of an epimerizable aldehyde and a beta-lactone.     

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.     

Total Synthesis of Antitumor Antibiotic Derhodinosylurdamycin A

The first total synthesis of derhodinosylurdamycin A, an angucycline antitumor antibiotic, has been described. The synthesis features a Hauser annulation followed by pinacol coupling to construct the tetracyclic angular aglycon, a Stille coupling of glycal stannane and tetracyclic aryliodide followed by stereoselective reduction to afford the 2‐deoxy β‐C‐arylglycoside, and a late‐stage stereoselective glycosylation for the preparation of derhodinosylurdamycin A. This synthetic strategy should be amenable to the chemical synthesis of analogs of derhodinosylurdamycin A bearing diverse 2‐deoxy sugar subunits for structure and activity relationship studies.     

The first total synthesis of nakadomarin A

(-)-Nakadomarin A is a member of manzamine alkaloid isolated from a marine sponge and have a unique hexacyclic structure. The first total synthesis of (+)-nakadomarin A, an enantiomer of natural product, has been accomplished from stereochemically defined 4-oxopiperidin-3-carboxylic acid derivative. The synthesis established the structure of nakadomarin A including absolute configuration.     

Synthesis of DNA-sequence-selective hairpin polyamide platinum complexes

Two DNA-sequence-selective hairpin polyamide platinum(II) complexes, containing pyrrole and imidazole heterocyclic rings, have been synthesised by different methods. A six-ring complex, selective for (A/T)GGG(A/T) DNA sequences, was made by using solid-phase synthesis, whilst an eight-ring complex, selective for (A/T)CCTG(A/T) DNA sequences, was made by utilising standard wet chemistry. Solid-phase synthesis resulted in a significantly higher yield, required less purification and is more efficient than the wet synthesis; as such, it is the preferred method for further work. The metal complexes were characterised by (1)H and (195)Pt NMR spectroscopy and ESI mass spectrometry. The two compounds provide a foundation for the synthesis of more complex molecules containing multiple hairpins and/or platinum groups.     

A stereoselective synthesis of (+)-herboxidiene/GEX1A

A stereoselective synthesis of (+)-herboxidiene is described. The convergent synthesis utilized a Suzuki cross-coupling reaction to assemble the key segments. The synthesis of the functionalized tetrahydropyran ring utilized an Achmatowicz reaction as the key step. The synthesis of the C10-C19 segment was accomplished using Brown's crotylboration, asymmetric alkylation, and a stereoselective allylic chlorination reactions.     

The total synthesis of (-)-callystatin A

Callystatin A is a prominent member of a class of natural products which display promising growth inhibition of cancer cells in their biological profile. The challenging structure and the interesting biological activity of (-)-callystatin A fueled our interest in the synthesis of this marine natural product. We achieved the total synthesis using a highly convergent approach joining four subunits together with a Wittig olefination, a selective Heck reaction and an aldol reaction as the pivotal steps. The aldol reaction as one of the final transformations during the synthesis opens fast access to a variety of structural analogues and circumvents tedious protecting group manipulations. Here we report an improved synthesis utilizing a modified vinyl iodide which shortens the synthesis by two steps. Additionally, first biological results will be reported.