Triptycene as a rigid, 120° orienting, three-pronged, covalent scaffold for porphyrin arrays

The synthesis of novel porphyrin trimers covalently linked by one central, rigid triptycene unit is described. Reaction of 2,6,14-triiodotriptycene, generated in a three-step synthesis from triptycene, with borylated porphyrins under Suzuki cross-coupling conditions afforded porphyrin trimers. In addition, Sonogashira cross-coupling conditions could be successfully applied for the synthesis of trimeric porphyrin arrays as well.     

Isolation, structure determination, and synthesis of neodysiherbaine A, a new excitatory amino acid from a marine sponge

[structure: see text] A new excitatory amino acid, neodysiherbaine A (2), was isolated as a minor constituent of the aqueous extract from the marine sponge Dysidea herbacea. The structure was deduced by spectroscopic methods and established unambiguously by the total synthesis. The present synthesis, including as a key step cross-coupling of the 6/5-bicyclic core with an amino acid residue, is useful in constructing its structural analogues.     

A short,stereocontrolled, and practical synthesis of alpha-methylomuralide,a potent inhibitor of proteasome function

An efficient and practical synthesis of alpha-methylomuralide (3), a selective inhibitor of proteasomes, has been developed as outlined in Scheme 1. Among the advantages of this route of synthesis over previously described approaches are (1) ease of scale-up and (2) high yields (28% overall yield of alpha-methylomuralide from 6) and stereocontrol (including high enantiocontrol). The synthesis is well suited to the production of 3 in the quantities needed for material-intensive in vivo investigations.     

RNA-protein cross-links induced by sensitization with a pyrroloquinolinone derivative, a furocoumarin analogue

The capacity of 2,6-dimethyl-9-methoxy-4H-pyrrolo [3,2,1-ij] quinolin-4-one (PQ), a furocoumarin analogue, of inhibiting protein synthesis in Ehrlich cells upon UVA irradiation was investigated. Using 8-methoxypsoralen (8-MOP) as a reference, we observed that in our short-term test the block of RNA synthesis do not affect protein synthesis, which is driven by pre-synthesised molecules of m-RNA; actually 8-MOP, studied at 100 μM concentration, practically abolished RNA synthesis without affecting significantly protein synthesis. Studying PQ sensitization in HL60 cells by alkaline elution and protein precipitation, the formation of covalent RNA-protein cross-links was observed. 8-MOP, assayed in severe experimental conditions, induced only moderate amounts of such lesion. On the basis of the data obtained in experiments carried out using various scavengers or exposing cells to UVA light in a nitrogen atmosphere, this damage appeared to be due to singlet oxygen formation, which is generated by PQ to a large extent. These results are consistent with the data obtained by H. Singh and J.A. Vadasz (Singlet oxygen: a major reactive species in the furocoumarin photosensitized inactivation of E. coli ribosomes, Photochem. Photobiol., 28 (1978) 539–545) on E. coli ribosomes. The lower activity we observed with 8-MOP might be attributed to a different sensitivity of whole mammalian cells in comparison with isolated ribosomes.     

Stereocontrolled total synthesis of a polyfunctional carotenoid, peridinin

Peridinin, which was isolated from the planktonic algae dinoflagellates causing red tides, is a highly oxidized carotenoid containing an allene and a characteristic (Z)-gamma-ylidenebutenolide function in the main conjugated polyene chain in addition to functionalized cyclohexane rings at both ends of the molecule. We achieved a stereocontrolled total synthesis of peridinin by featuring the Sharpless asymmetric epoxidation under precise reaction conditions, Wittig reaction with silylfuranmethylide followed by photosensitized oxygenation, stereocontrolled Pd-catalyzed one-pot (Z)-gamma-ylidenebutenolide synthesis, and modified Julia-Kocienski olefination. This synthesis is the first example of controlling the stereochemistry of polyfunctional allenic carotenoids.     

Application of a Double Aza-Michael Reaction in a 'Click, Click, Cy-Click' Strategy: From Bench to Flow

The development of a 'click, click, cy-click' process utilizing a double aza-Michael reaction to generate functionalized 1,2,5-thiadiazepane 1,1-dioxides is reported. Optimization in flow, followed by scale out of the inter-/intramolecular double aza-Michael addition has also been realized using a microwave-assisted, continuous flow organic synthesis platform (MACOS). In addition, a facile one-pot, sequential strategy employing in situ Huisgen cycloaddition post-double aza-Michael has been accomplished, and is applicable to library synthesis.     

Synthesis of Atisine,Ajaconine, Denudatine,and Hetidine Diterpenoid Alkaloids by a Bioinspired Approach

A unified approach to four different (atisine, ajaconine, denudatine, and hetidine) diterpenoid alkaloid skeletons was developed and applied to the total synthesis of the natural products dihydroajaconine ( 2 , atisine type) and gymnandine ( 4 , denudatine type). The synthesis features a biogenetically inspired strategy that relies on C−H oxidation, aza‐pinacol coupling, and aza‐Prins cyclization as key steps.     

Synthesis of Atisine,Ajaconine, Denudatine,and Hetidine Diterpenoid Alkaloids by a Bioinspired Approach

A unified approach to four different (atisine, ajaconine, denudatine, and hetidine) diterpenoid alkaloid skeletons was developed and applied to the total synthesis of the natural products dihydroajaconine ( 2 , atisine type) and gymnandine ( 4 , denudatine type). The synthesis features a biogenetically inspired strategy that relies on C?H oxidation, aza‐pinacol coupling, and aza‐Prins cyclization as key steps.     

Stereoselective synthesis of a tetrahydropyranyl diarylheptanoid,ent-diospongin A

The stereoselective synthesis of the unnatural enantiomer of a cyclic diarylheptanoid, diospongin A is described. The salient feature of this synthesis is the formation of a tetrahydropyran ring via the AgOTf-catalysed intramolecular oxa-Michael addition of a β-hydroxy ynone followed by hydrogenation     

The synthesis of 3-hydroxymethyldibenzo[b,f]thiepin 5,5-dioxide,a prostaglandin antagonist

An economic synthesis of 3-hydroxymethyldibenzo[b,f]thiepin 5,5-dioxide, a novel prostaglandin antagonist, is described. The key step in the synthesis is the formation of a carboxyphenylacetic acid by carboxylation of a toluic acid dianion, followed by cyclisation to the tricyclic ketone. Readily available starting materials are used in the synthesis and conditions have been found at each stage to give pure intermediates, requiring little purification, in high yield.     

Spatial photorelease of oligonucleotides, using a safety-catch photolabile linker

[reaction: see text] We report the development of a safety-catch photolabile linker that allows the light-directed synthesis and spatially selective photorelease of oligonucleotides from microarrays. The linker remains stable to light during DNA synthesis, and is activated for photorelease after acidic hydrolysis. We demonstrate that the photoreleased oligonucleotides can be amplified by PCR to produce double stranded DNA. The advantages offered by this linker could aid the development of an automated gene synthesis platform.     

Synthesis, Reactivity, and Resolution of a C(2)-Symmetric, P-Stereogenic Benzodiphosphetane, a Building Block for Chiral Bis(phosphines)

Although the pyramidal inversion barriers in diphosphines (R(2)P-PR(2)) are similar to those in phosphines (PR(3)), P-stereogenic chiral diphosphines have rarely been exploited as building blocks in asymmetric synthesis. The synthesis, reactivity, and resolution of the benzodiphosphetane trans-1,2-(P(t-Bu))(2)C(6)H(4) are reported. Alkylation with MeOTf followed by addition of a nucleophile gave the useful C(2)-symmetric P-stereogenic ligand BenzP* and novel analogues.     

Total synthesis of a new cytotoxic acetogenin, jimenezin, and the revised structure

The first total synthesis of jimenezin was achieved by using carbohydrates as chiral building blocks, thus revising the proposed structure 1 to 2. The key steps in this synthesis include an efficient construction of the THP-THF fragments 3 and 16 through a stereoselective condensation between the pyranyl aldehyde 5 and the acetylene derivative 6, and a palladium-catalyzed coupling reaction of 3 or 16 with a terminal butenolide 4.     

Asymmetric total synthesis of 11-deoxytetrodotoxin,a naturally occurring congener

Tetrodotoxin, a toxic principle of puffer fish poisoning, is a specific blocker of sodium channel. Despite many synthetic efforts since the structure elucidation in 1964, the only total synthesis of the racemic tetrodotoxin has been reported by Kishi and co-workers. In the course of our studies directed toward the total synthesis to analyze biologically interesting issues associated with tetrodotoxin, we accomplished a highly stereocontrolled synthesis of (-)-5,11-dideoxytetrodotoxin in 1999. Based on the synthesis, we describe herein the first total synthesis of 11-deoxytetrodotoxin, a naturally occurring analogue. The synthesis started from an allylic alcohol, the same intermediate for the synthesis of 5,11-dideoxytetrodotoxin. Epoxidation of the allylic alcohol was followed by isomerization with Ti(i-PrO)(4) to give an alpha-hydroxy allylic alcohol, in which the configurations of the two hydroxyl groups were inverted by oxidation and then a 2-step reduction. Further epoxidation of the allylic alcohol and ozonolysis of the remaining vinyl group gave an aldehyde, which reacted with magnesium acetylide to give a propargyl alcohol in a stereoselective manner. Oxidative cleavage of the acetylenic moiety with RuO(4) afforded a fully functionalized lactone for 11-deoxytetrodotoxin. Crucial guanidinylation was achieved from trichloroacetamide according to our own method to give acetyldibenzylguanidine. Finally, deprotection of benzyl groups, acetates, and acetal furnished 11-deoxytetrodotoxin.     

Enantioselective total synthesis of (-)-acetylaranotin, a dihydrooxepine epidithiodiketopiperazine

The first total synthesis of the dihydrooxepine-containing epidithiodiketopiperazine (ETP) (-)-acetylaranotin (1) is reported. The key steps of the synthesis include an enantioselective azomethine ylide (1,3)-dipolar cycloaddition reaction to set the absolute and relative stereochemistry, a rhodium-catalyzed cycloisomerization/chloride elimination sequence to generate the dihydrooxepine moiety, and a stereoretentive diketopiperazine sulfenylation to install the epidisulfide. This synthesis provides access to (-)-1 in 18 steps from inexpensive, commercially available starting materials. We anticipate that the approach described herein will serve as a general strategy for the synthesis of additional members of the dihydrooxepine ETP family.     

Synthesis of a LEC14 nonasaccharide, a core-fucosylated, biantennary N-glycan with a novel GlcNAc residue in the core region

The recently found core substitution of N-glycans termed LEC14 is characterized by a GlcNAc residue linked β(1,2) to the central β-mannoside. Starting from a pentasaccharide building block functionalized for core-fucosylated N-glycans the total synthesis of a protected LEC14 nonasaccharide was accomplished. The key step of the synthesis was the introduction of the additional β(1,2)-linked GlcNAc residue that was highly dependent on the solvent and appears to proceed via an amide acetal intermediate.     

Synthesis of balsaminone A, a naturally occurring pentacyclic dinaphthofuran quinone

A short synthesis of the natural product balsaminone A, a dinaphthofuran quinone, is described. The key steps of the synthesis are base-induced coupling of 1,4-dihydroxy-2-naphthaldehyde with 2,3-dichloronaphthoquinone to give a pentacyclic dinaphthofuran directly, followed by conversion of the aldehyde into the desired methoxy group via the corresponding phenol. The synthesis, in which the structure of a key pentacyclic intermediate is corroborated by X-ray crystallography, confirms the original structural assignment of the natural product.     

Asymmetric synthesis of a chiral buckybowl, trimethylsumanene

The first asymmetric synthesis of a chiral buckybowl, a C3 symmetric (C)-8,13,18-trimethylsumanene (1), was achieved by employing a synthetic strategy that translates chirality at sp3 centers into bowl chirality. The synthesis features a syn selective cyclotrimerization of an enantiopure halonorbornene derivative, tandem ring-opening/closing olefin metathesis reactions, and DDQ oxidation at low temperature. The bowl-to-bowl inversion energy of 1 was determined as 21.6 kcal/mol by circular dichroism spectra measurement.     

Practical synthesis of 16,22-diketocholesterol acetate, a precursor of anticancer saponin OSW-1, from diosgenin

An improved method using dibromide protection of the 5,6-double bond has been developed for the synthesis of the title compound, which is a key intermediate in the synthesis of saponin OSW-1 from diosgenin.     

Total Synthesis of Carthamin,a Traditional Natural Red Pigment

The first total synthesis of carthamin ( 3 ), a historic natural red pigment, has been achieved. The molecular structure was efficiently constructed by assembling two equivalents of the in situ generated lithiated monomers and triisopropyl orthoformate. This synthesis confirms the structure proposed in 1996.