Enantiospecific first total synthesis of 7a(S)-p-hydroxyphenopyrrozin

An enantiospecific first total synthesis of metabolite 7a(S)-p-hydroxyphenopyrrozin 2, isolated from the cultured fungi Chromocleista sp. has been achieved starting from readily and abundantly available l-proline. The strategy of synthesis utilizes base mediated cyclization and base mediated oxygenation as the key steps.     

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*.     

A simple and efficient enantioselective route to 2,6-disubstituted piperidines: synthesis of (2R,6S)-isosolenopsin A and (2S,6R)-isosolenopsin

The enantioselective synthesis of 2,6-cis-disubstituted piperidine alkaloids, (2R,6S)-isosolenopsin A 2 and (2S,6R)-isosolenopsin 5 from fire ant venom is described. Starting from the dodecanal and decanal, the synthesis presents two key steps. The first step involves Keck allylation to afford the chiral homoallylalcohol with the required stereochemistry and the second key step consists of Grubbs olefin cross metathesis. The synthesis was achieved in five steps with 44% overall yield.     

A type 2 Ferrier rearrangement-based synthesis of d-myo-inositol 1,4,5-trisphosphate

The synthesis of d-myo-inositol 1,4,5-trisphosphate (InsP₃) from methyl α-d-glucopyranose, via a type 2 Ferrier rearrangement is reported. A key intermediate in this synthesis possesses orthogonal protecting groups at the 1-, 4- and 5-position, making it a versatile starting point for the synthesis of unnatural InsP₃ derivatives. Biological evaluation of the synthetic InsP₃ demonstrates that this compound evokes selective Ca²⁺ release via activation of InsP₃ receptors.     

Asymmetric synthesis of 3,4-dihydroxyglutamic acids via enantioselective reduction of cyclic meso-imide

Stereoselective synthesis of (3S,4S)- and (3R,4R)-series of 3,4-dihydroxyglutamic acids was investigated. The key reaction in this synthesis is asymmetric reduction of meso-imide derived from meso-tartaric acid. Lewis acid-promoted cyanation of the obtained optically active lactam via the acyliminium intermediate followed by standard deprotection procedure afforded the desired 3,4-dihydroxyglutamic acids.     

An efficient enantioselective synthesis of florfenicol via asymmetric aziridination

An efficient enantioselective synthesis of florfenicol is accomplished in 44.7% overall yield from commercially available p-(methylsulfonyl)benzaldehyde. Key features of this synthesis are the asymmetric aziridination reaction mediated by the Wulff’s catalyst in situ derived from (R)-VANOL and diastereoselectively ring-opening of (2S,3S)-fluoroaziridine 13.     

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.     

Asymmetric synthesis of a dopamine D1 agonist,dihydrexidine from d-serine

A scalable asymmetric synthesis of trans-2-amino-6,7-dimethoxy-1-phenyltetralin 2 and its N-nosyl derivative 12 have been achieved from Garner aldehyde derived from easily available d-serine using a stereoselective PhMgBr addition, Wittig reaction and TFA-mediated Friedel–Crafts cyclization as the key steps. The synthesis of dihydrexidine is accomplished from the N-nosyl-2-amino-1-phenyltetralin 12.     

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.     

Asymmetric synthesis of tert-butyl ((1R,4aR,8R,8aR)-1-hydroxyoctahydro-1H-isochromen-8-yl)carbamate

The asymmetric synthesis of methyl (E)-4-((1R,2S,3R)-3-amino-2-((E)-2-methoxycarbonyl-eten-1-yl)cyclohexyl)but-2-enoate 14 has been achieved from dimethyl (2E,7E)-nona-2,7-dienedioate 2. A key step is the asymmetric synthesis of 1-hydroxyoctahydro-1H-isochromene derivative 5 whose X-ray analysis corroborated the stereochemistry of the new stereocenters. The asymmetric synthesis of the isochromenyl acetate derivative 11 shows the potential of this methodology for fused cyclohexanic system heterocyclic synthesis.     

Stereoselective synthesis of (+)-sordidin, the male-produced aggregation pheromone of the banana weevil Cosmopolites sordidus

Stereoselective synthesis of (1S,3R,5R,7S)-(+)-sordidin, the natural male-produced aggregation pheromone of the banana weevil Cosmopolites sordidus (Germar) starting from 5-benzyloxy-(2E)-pentene-1-ol is described. The key transformations employed in the synthesis are Sharpless asymmetric epoxidation, Ueno-Stork cyclization, and Jacobsen kinetic resolution.     

First enantioselective total synthesis of (−)-dysibetaine CPa and absolute configurations of natural product

Here we report total synthesis of enantiomerically pure dysibetaine CPa, isolated from Micronesian marine sponge and expected to serve as a neuroactive agent. Starting from meso-cyclopropane triester, the synthesis was achieved in 12.8% overall yield over 10 steps including organocatalytic enantioselective solvolysis of meso-succinic anhydride as a key step. This work established the absolute configurations of the natural product as (3R,4R).     

The first synthesis of ent-agelasine F

Agelasine F has previously been isolated from marine sponges (Agelas sp.) and has been associated with various bioactivities including inhibitory activity on Mycobacterium tuberculosis. No total synthesis of this natural product has been reported. ent-Agelasine F has now been synthesized for the first time, starting from (R)-pulegone. The synthesis is considerably more efficient than a previously reported route to rac-agelasine F. ent-Agelasine F is found to exhibit antimicrobial activity.     

An easy and versatile approach to the synthesis of chiral pheromone lactones via 4,4-dimethyl-2-oxazoline derivatives

As part of our ongoing investigation on the versatility of 4,4-dimethyl-2-oxazoline derivatives, we present a straightforward synthesis of chiral lactone pheromones from readily available starting materials. As an application, we describe the diastereoselective synthesis of cis and trans-2-methyl-5-hexanolide (1), a pheromone component of the carpenter bee Xylocopa hirutissima, and a formal synthesis of (4R,5Z)-5-tetradecen-4-olide (2), the sex pheromone of the Japanese beetle Popillia japonica.     

Asymmetric synthesis of (S)-homocitric acid lactone

Starting from (S)-phenylalanine, an asymmetric synthesis of (S)-homocitric acid lactone was achieved using Seebach’s SRS methodology. An intermediate for the synthesis of the (S)-per-homocitric acid lactone has also been synthesized.     

The effect of inert additives on the explosive mechanochemical synthesis of some metal chalcogenides

The effect of different inert additives on the mechanochemical synthesis of SnS was studied. A transition from explosive to nonexplosive mechanochemical reaction was observed. It was shown that this change takes place only when a critical volume x_c is occupied by inert material. The critical volume for a transition from an explosive to nonexplosive mechanochemical synthesis were determined for the chalcogenides of Zn, Cd, and Sn. The x_c values obtained are discussed. On the basis of the new data concerning the critical dimensions r_c of the exploding mechanical aggregates and the percolation phenomena, a mechanism for the transition from an explosive to nonexplosive mechanochemical synthesis is suggested.     

Reactivity of azafulvenium methides derived from pyrrolo[1,2-c]thiazole-2,2-dioxides: synthesis of functionalised pyrroles

Extrusion of sulfur dioxide from pyrrolo[1,2-c]thiazole-2,2-dioxides led to the synthesis of functionalised pyrroles via the generation of 1-azafulvenium methides. Sealed tube reaction conditions allowed the synthesis of N- and C-vinylpyrroles whereas from FVP methyl 1,3-dimethyl-5-oxo-5H-pyrrolizine-2-carboxylate and 4-oxo-1,4-dihydro-1-aza-benzo[f]azulene-3-carboxylates were obtained. These last compounds could also be obtained from the FVP of the N- and C-vinylpyrroles.     

Total synthesis of calystegine A7

A straightforward chiral pool synthesis for the glycosidase inhibitor calystegine A₇ (isolated from Lycium chinense) from methyl α-d-glucopyranoside is described. Keysteps of this synthesis include a ultrasound assisted Zn-mediated tandem ring opening reaction followed by a Grubbs' catalyst mediated ring closure metathesis.     

Stereoselective synthesis of 1,4-dideoxy-1,4-imino-d-allitol and formal synthesis of (2S,3R,4S)-3,4-dihydroxyproline

A stereoselective synthesis of 1,4-dideoxy-1,4-imino-d-allitol 1 and formal synthesis of (2S,3R,4S)-3,4-dihydroxyproline was achieved via the addition of vinylmagnesium bromide to the benzylimine derived from (R)-2,3-O-isopropylidene glyceraldehyde followed by N-allylation, ring-closing metathesis (RCM), and dihydroxylation.     

Rapid and convenient semi-automated microwave-assisted solid-phase synthesis of arylopeptoids

A facile and expedient route to the synthesis of arylopeptoid oligomers (N-alkylated aminomethyl benz-amides) using semi-automated microwave-assisted solid-phase synthesis is presented. The synthesis was optimized for the incorporation of side chains derived from sterically hindered or unreactive amines and both ortho- and para-substituted arylo-backbones. By utilizing this optimized protocol a complex nonameric arylopeptoid was synthesized in less than 11 h, featuring a novel alternating ortho-, meta-, and para-substituted backbone pattern and a variety of chemically diverse and challenging side chains.