A flexible organocatalytic enantioselective synthesis of heptadeca-1-ene-4,6-diyne-3S,8R,9S,10S-tetrol and its congeners

A unified enantioselective route is developed for the synthesis of heptadeca-1-ene-4,6-diyne-3S,8R,9S,10S-tetrol and its synthetic congeners. A proline-catalyzed aminoxylation, cross-metathesis, Wittig reaction, and catalytic dihydroxylation are key steps of this synthesis. This new approach is envisioned to facilitate the synthesis of every representative member of the family with skeletal and stereochemical variation.     

A new, improved synthesis of the trisaccharide repeating unit of the O-antigen from Xanthomonas campestris pv. campestris 8004

Recent studies have revealed that lipid-A and core fragments of the lipopolysaccharide from Xanthomonas campestris pv. campestris 8004 (Xcc), a phytopathogenic Gram-negative bacterium, are able to elicit plant immunity with two independent mechanisms. To date, nothing is known about the effect of the O-antigen portion. Since its separation from the core region by selective chemical degradation is very difficult, the chemical synthesis of related oligosaccharides is strictly necessary. In this paper a new, improved synthesis of the O-antigen repeating unit is presented. The main improvements in the synthesis are: (1) a shorter, high-yielding preparation of an efficient glycosyl donor of the rare sugar 3-acetamido-3,6-dideoxy-d-galactopyranose (3-acetamido-d-fucose, d-Fucp3NAc); (2) a new protecting group pattern, which is demonstrated to open a path to the future synthesis of higher oligomers.     

Synthesis of cyclitols via ring-closing metathesis

A convenient synthesis of enantiomerically pure and differentially protected l-chiro- and myo-inositols as well as conduritols B and F from 2,3,4-tri-O-benzyl-d-xylopyranose via ring-closing metathesis is reported. The facile synthesis of conduritol B constitutes a short formal synthesis of (−)-cyclophellitol.     

A facile route for the synthesis of vinyl-substituted 1,3,4-oxadiazoles

An efficient synthesis of vinyl-substituted 1,3,4-oxadiazoles using o-nitrophenyl sulfoxide precursor via syn-elimination reaction using sodium acetate in THF is described. This method is cost effective as it uses cheap o-nitrothiophenol and can be used in the synthesis of vinyl intermediates during synthesis of bioactive compounds, which avoids the use of any toxic metals.     

An improved and general synthesis of monomers for incorporating trityl linker groups into polystyrene synthesis supports

A straightforward synthesis of trityl alcohols in which one of the aryl rings is substituted with a vinyl group is presented. The synthesis of the alcohols involves the direct addition of the Grignard reagent prepared from 4-bromostyrene to substituted benzophenones. These compounds are used to incorporate trityl linker groups into polystyrene-based organic synthesis supports. Both non-cross-linked and cross-linked (JandaJel™) polystyrene have been prepared using these monomers.     

First total synthesis of glabramycin B and revision of its relative configuration

Structural revision of glabramycin B, which is an antibacterial 10-membered lactone isolated from a fermentation broth of Neosartorya glabra, was achieved by enantioselective synthesis of our proposed structure. The correct structure of glabramycin B was presumed on comparison with related compounds, and synthesis of it was succeeded via dianion alkylation, Shiina's lactonization and Stille cross-coupling. By this synthesis, we were able to correct the reported structural misassignment, and to confirm the relative configuration of glabramycin B to be 10S*,11S*,15R*,20S*.     

Synthetic studies towards dendridine A: synthesis of hemi-dendridine A acetate by Fischer indolization

A short synthesis of hemi-dendridine A acetate has been accomplished. The synthesis is based on a modified Fischer indolization that represents a rare example of the single-step synthesis of a 7-oxytryptamine from an ortho-oxygenated phenylhydrazine. The synthetic route required developing an efficient synthesis of N-acetyl-2-pyrroline, the key coupling partner for the modified Fischer indolization. Some interesting chemistry associated with the abnormal Fischer indolization has been uncovered, whereby two molecules of the phenylhydrazine substrate combined along the abnormal reaction pathway, affording an unusual N-phenylindoleamine product.     

One-step synthesis of [1]benzothieno[3,2-b][1]benzothiophene from o-chlorobenzaldehyde

Simple one-step synthesis of [1]benzothieno[3,2-b][1]benzothiophene (BTBT) from commercially available o-chlorobenzaldehyde is reported. The procedure is also applicable to the synthesis of dinaphtho[2,3-b:2′,3′-f]thieno[3,2-b]thiophene (DNTT).     

Facile synthesis of a cis-syn thymine dimer building block and its incorporation into oligodeoxynucleotides

The synthesis of a building block containing the photobiologically relevant cis-syn thymine cyclobutane photoproduct and its incorporation into oligonucleotides by the phosphoramidite-based solid-phase synthesis is reported. Compared to previous syntheses, this route is extremely short and allows such modified oligonucleotides to be easily available for biological studies.     

Exploiting morph-DAST mediated ring-expansion of substituted cyclic β-amino alcohols for the preparation of cyclic fluorinated amino acids. Synthesis of 5-fluoromethylproline and 5-fluoropipecolic acid

The synthesis of proline analogues bearing a fluorine-containing substituent at the fifth position of the pyrrolidine ring, racemic trans- and cis-5-fluoromethyl prolines, was performed. The key step of the synthesis is a transformation of the CH₂OH-group into the CH₂F-one using morpholinosulfur trifluoride. During the synthesis, an efficient procedure to prepare trans- and cis-5-fluoropipecolic acids was elaborated.     

Iterative synthesis of the ABCDEF-ring system of yessotoxin and adriatoxin

A stereocontrolled linear synthesis of the ABCDEF-ring system of yessotoxin and adriatoxin, diarrhetic shellfish toxins, is described. Iterative application of a tetrahydropyran synthesis by reaction of the alkylation of a sulfonyl-stabilized oxiranyl anion followed by 6-endo cyclization of a 4,5-epoxy alcohol led to the synthesis of the trans-fused hexacyclic ether system, and the seven-membered E ring was constructed by ring expansion reaction.     

Enantiospecific synthesis of 3-aza-6,8-dioxa-bicyclo[3.2.1]octane carboxylic acids from erythrose

New methodology for the synthesis of enantiopure 3-aza-6,8-dioxa-bicyclo[3.2.1]octane-carboxylic acids belonging to 7-endo-BTAa sub-class of γ/δ amino acids is described. The novelty is the use of 2,3-O-isopropylidene-erythrose instead of meso-tartaric acid derivative, thus allowing us to perform an enantiospecific synthesis. Reductive amination of erythrolactol with aminoacetaldehyde diethylacetal or benzylamine, and subsequent acid cyclisation gave directly the amino alcohol scaffold. Protection of nitrogen as urethane and final alcohol oxidation afforded the Fmoc-, Boc-, and Cbz-amino acids. The new synthetic route was applied to multigram scale, thus resulting in a marked improvement of the synthesis of enantiopure 7-endo-BTG and 7-endo-BTK amino acids.     

Total synthesis of 4-epi-atpenin A5 as a potent nematode complex II inhibitor

It is clear that atpenins and their analogs are useful chemical tools for elucidation of complex II functionality and that they could act as lead compounds for the development of novel helminth complex II-specific inhibitors. Recently, we discovered 4-epi-atpenin A5 as a potent nematode complex II inhibitor during our SAR studies of atpenin A5. This result led us to embark on a concise total synthesis of 4-epi-atpenin A5. In this study, we describe the total synthesis of 4-epi-atpenin A5. Importantly, this was more concise and practical synthesis than our previous total synthesis of atpenin A5.     

Synthetic studies towards Pseudoxylallemycin B,an antibiotic active against gram-negative bacteria: Total synthesis of 3-epi-Pseudoxylallemycin B

In an attempt towards the total synthesis of Pseudoxylallemycin B, a homo dimeric, N-methylated macrocyclic tetrapeptidic natural product, synthesis of its epimer at position 3 (d-Tyr instead of l-Tyr) is described here. During the course of synthesis we came across a striking yet unusual observation of complete epimerization which led to the formation of 3-epi-Pseudoxylallemycin B.     

An expedient synthesis of salviadione

An expedient synthesis of the alkaloid salviadione, the only to date isolated naturally occurring 1H-benzo[def]carbazole is described. The key step in the synthesis is a palladium-catalyzed, carbon monoxide-mediated reductive N-heterocyclization of a nitroarene with an adjacent alkene.     

Stereoselective nitrenium ion cyclizations: asymmetric synthesis of the (+)-Kishi lactam and an intermediate for the preparation of fasicularin

The asymmetric synthesis of the (+)-Kishi lactam and an intermediate for the preparation of the marine natural product fasicularin is reported. The keystone of this divergent synthesis is the diastereoselective azaspirocyclization of an N-methoxy γ-arylbutanoamide, which is believed to proceed through the intermediacy of an N-acylnitrenium ion.     

Total synthesis of malayamycin A and analogues

The total synthesis of the bicyclic C-nucleoside malayamycin A is described starting with d-ribonolactone. A new method was developed to obtain preparatively important quantities of β-pseudouridine, which was used as an intermediate. The synthesis of a carba N-nucleoside analogue of malayamycin A is also described.     

Formal total synthesis of aspergillides A and B

The formal total synthesis of the cytotoxic 14-membered macrolides, aspergillides A and B is described. A combination of a chiron approach and an asymmetric synthesis is adopted for the synthesis of the target macrolides. The required 2,6-syn and 2,6-anti tetrahydropyrans were constructed via a tandem Sharpless asymmetric epoxidation and 6-exo cyclization on δ-hydroxy allylic alcohols, as the key steps. The requisite chiral synthon was prepared from l-ascorbic acid.     

Cu(I)-catalyzed reaction of diazo compounds with terminal alkynes: a direct synthesis of trisubstituted furans

A method for the synthesis of tri-substituted furans has been developed based on Cu(I)-catalyzed reaction of terminal alkynes with β-keto α-diazoesters. This method for the synthesis of 2,3,5-trisubstituted furans is operationally simple and applicable to wide substrate scope. Moreover, this synthesis employs cheap Cu(MeCN)₄PF₆ as the catalyst and no additional ligand is needed. Similar reaction has also been applied to ethyl (E)-2-diazo-3-(methoxyimino)butanoate for the synthesis of 2,3,5-trisubstituted N-methoxypyrroles with limited success.     

Stereoselective synthesis of (+)-(8R,8aR)-perhydro-8-indolizidinol

A highly stereoselective total synthesis of (+)-(8R,8aR)-perhydro-8-indolizidinol is described. Key steps involved in this synthesis are diastereoselective zinc allylation, azido-olefin cyclization and reductive amination followed by cyclization which effectively constructed the indolizidine ring. This contributes a unique approach to the synthesis of indolizidine alkaloids that offers the advantages of brevity and relatively high overall yields.