Syntheses in enantiopure form of four diastereoisomeric naphthopyranquinones derived from aphid insect pigments

The first syntheses are described of the four enantiopure naphthopyranquinones (1R,3R,4S)- and (1R,3R,4R)-3,4-dihydro-4,7,9-trihydroxy-1,3-dimethylnaphtho[2,3-c]pyranquinone (quinone A 1 and quinone A' 2) and their two C-3 epimers, the (1R,3S,4S)- and (1R,3S,4R)-diastereoisomers 5 and 6, using enantiopure lactate as the source of asymmetry. Key factors in these syntheses are the maintenance of stereochemical integrity throughout the sequences and intramolecular diastereoselective cyclisations of the titanium phenolates of phenolic lactaldehydes. For these cyclisations the differing degree of diastereoselectivity is explained as are the stereochemistries of the product 2-benzopyran-4,5-diols.     

Rhodium-catalyzed cyclohydrocarbonylation approach to the syntheses of enantiopure homokainoids

Homologues of kainic acid, a naturally occurring potent glutamate receptor agonist, were designed based on a rigidified pipecolinoglutamic acid structure and can be regarded as homokainoids for their potential activities in the central nervous system. These novel homokainoids in an enantiomerically pure form were synthesized from enantiopure (R)- and (S)-Garner's aldehyde, featuring (i) the highly diastereoselective addition of alkenylcuprates to the acrylate intermediates and (ii) the Rh-catalyzed cyclohydrocarbonylation of homoallylic amine intermediates to construct the functionalized piperidine moiety in the key steps. For the introduction of a substituent at the 4- or 5-position of pipecolinoglutamic acid, a few different strategies were used, which successfully led to the formation of enantiopure homokainoids.     

Novel stereoselective synthesis of enantiopure (+)-N-Boc-norpandamarilactonine-A, the intermediate for pandamarilactonines

A novel synthesis of enantiopure N-Boc-norpandamarilactonine-A was established by employing a double ring-closing metathesis of a tetraene derivative, as a key step, where two five-membered rings were constructed in one step. N-Boc-Norpandamarilactonine-A was also converted to ent-norpandamarilactonine-A, and subsequently to pandamarilactonine-A and B.     

A stereoselective synthesis of (+/-)-C-secolimonoid BCDE model compounds related to the insect antifeedant ohchinolide.

A short and stereoselective synthesis of a (+/-)-BCDE C-secolimonid model insect antifeedant related to ohchinolide and nimbolidin was accomplished in 13 (30% overall yield) and 15 (30% overall yield) steps, respectively, from ethyl drimanate. The key steps are the torquoselective electrocyclization of the divinyl ketone 6, induced by perchloric acid, and the stereoselective rearrangement of the hydroxy lactone 12, inspired in a biosynthetic proposal. An alternative route, which provides access to (+/-)-BCDE ohchinolide and nimbolidin isomers, is also described.     

Influence of HMPA on the stereochemical outcome of the addition of a racemic allenylzinc onto enantiopure N-tert-butanesulfinimines: stereoselective access to enantiopure cis-ethynylaziridines

In the presence of 60 equivalents of HMPA, the condensation of the racemic allenylzinc derived from 1-chloro-3-trimethylsilylpropyne onto enantiopure non-alpha-branched N-tert-butanesulfinimines was proven to give access to the corresponding cis-ethynylaziridines as the major products. The good cis selectivity observed presumably resulted from a high kinetic resolution with the allenylzinc being partially configurationally labile with respect to the time scale defined by the rate of the reaction. Both single crystal X-ray analysis and semiempirical calculations conducted at the MM2 and AM1 levels of theory proved that the reaction certainly occurred through a preferred synclinal transition state in a supra- or antarafacial S(E)2' process. In all cases, chromatographic purification over silica gel allowed the cis-ethynyl-N-tert-butanesulfinylaziridines to be obtained as diastereo- and enantiomerically pure compounds (dr >98:2 and ee >99%).     

Highly stereoselective chemoenzymatic synthesis of the 3H-isobenzofuran skeleton. Access to enantiopure 3-methylphthalides

A straightforward synthesis of (S)-3-methylphthalides has been developed, with the key asymmetric step being the bioreduction of 2-acetylbenzonitriles. Enzymatic processes have been found to be highly dependent on the pH value, with acidic conditions being required to avoid undesired side reactions. Baker's yeast was found to be the best biocatalyst acting in a highly stereoselective fashion. The simple treatment of the reaction crudes with aqueous HCl has provided access to enantiopure (S)-3-methylphthalides in moderate to excellent yields.     

Convergent, stereoselective syntheses of the glycosidase inhibitors broussonetines C, O and P

The first syntheses of the polyhydroxylated alkaloids (iminosugars) broussonetines O and P, glycosidase inhibitors of the pyrrolidine class, have been performed in a convergent, stereocontrolled way from d-serine as the chiral starting material. The synthesis of broussonetin C, a further member of this compound family, is also reported. A cross-metathesis step was one key feature of the synthesis. The versatility of the synthetic concept chosen permits the access to many members of this compound family, both natural ones and analogues thereof.     

An approach to the stereoselective synthesis of enantiopure dihydropyrroles and aziridines from a common sulfinyl-sulfinamide intermediate

The diastereoselective addition of lithiated vinyl sulfoxides to enantiopure sulfinimines provides direct access to a wide assortment of allylic sulfinamides in good yields and excellent selectivities. These adducts are key precursors to differently functionalized cis- and trans-dihydropyrroles. Modulation of the protecting group on nitrogen prior to cyclization has a significant impact on the stereochemical outcome, allowing for the selective preparation of 2,5-cis- or 2,5-trans-3-sulfinyl disubstituted dihydropyrroles from a common sulfinamide intermediate. Further research on halocyclization conditions has also yielded a stereoselective synthesis of trisubstituted vinyl aziridines from these chiral sulfinamides, simply by changing the halogenating agent.     

Studies on the identification and syntheses of insect pheromones XXI stereoselective synthesis of all the possible optical isomers of the mosquito oviposition attractant pheromone

All the four optical isomers of the oviposition attractant pheromone of the mosquito $\text{Gulex pipiens fatigans}$ were synthesized via Sharpless asymmetric epoxidation.     

Chiral pyridin-3-ones and pyridines: syntheses of enantiopure 2,4-disubstituted 6-hydroxy-1,6-dihydro-2H-pyridin-3-ones, 2,3-disubstituted 4-iodopyridines, and enantiopure 2,3-disubstituted 4-pyridinemethanols

The development of an innovative method to access enantiopure 2,4-disubstituted 6-hydroxy-1,6-dihydro-2H-pyridin-3-ones starting from D-glucal via the aza-Achmatowicz transformation has been described. These highly functionalized pyridin-3-ones have been utilized for the synthesis of contiguously substituted pyridines through a rapid and efficient Et(3)N/Ac(2)O promoted cyclo-elimination, aromatization cascade, allowing the facile assembly of important pyridine-based building blocks like 2-substituted 3-acetoxy-4-iodopyridines and enantiopure 2-substituted 3-acetoxy-4-pyridinemethanols possessing benzylic stereogenic centers, whose synthesis otherwise would be tedious. The utilization of commercially available sugars as starting materials, mild reaction conditions, catalytic transfer hydrogen (CTH) of α-furfuryl azide derivatives, transfer of chiral aryl/alkyl methanols from enulosides to pyridin-3-ones and pyridines, high yields, and short reaction times are key features of this method. The utility of the method has been further exemplified by demonstrating the usage of the 2-substituted 3-acetoxy-4-iodopyridine for the construction of biologically significant molecules like 2,7-disubstituted furo[2,3-c]pyridines and 7,7'-disubstituted 2,2'-bifuro[2,3-c]pyridines.     

昆虫信息素结构鉴定与合成 XXI, 淡色库蚊产卵引诱信息素四个光学异构体的立体选择性合成

应用Sharless不对称环氧化反应,合成淡色库蚊产卵引诱信息素的所有四个光学异构体1a～1d, e.e.96～97%. 从炔醇2出发到1a～1d的总得率为15～20%.     

Sequential organocatalyzed Michael addition/[3 + 2]-heterocyclization for the stereoselective synthesis of fused-isoxazoline precursors of enantiopure cyclopentanoids

We propose an asymmetric synthesis of functionalized cyclopentanoids bearing up to four stereogenic centers from easily accessible nitroalkenes and unsaturated aldehydes. The overall sequence includes an enantioselective organocatalytic Michael addition and a [3 + 2]-heterocyclization between an in situ generated silylnitronate and the unactivated double bond. Finally, the fused isoxazoline can be further transformed to various cyclopentanoids.     

Nitrile biotransformations for the efficient synthesis of highly enantiopure 1-arylaziridine-2-carboxylic acid derivatives and their stereoselective ring-opening reactions

Catalyzed by the Rhodococcus erythropolis AJ270 whole cell catalyst under very mild conditions, biotransformations of racemic 1-arylaziridine-2-carbonitriles proceeded efficiently and enantioselectively to produce highly enantiopure S-1-arylaziridine-2-carboxamides and R-1-arylaziridine-2-carboxylic acids in excellent yields. Although the nitrile hydratase exhibits no selectivity against all nitrile substrates, the amidase is highly R-enantioselective towards 1-arylaziridine-2-carboxamides. When treated with benzyl bromide, 1-phenylaziridine-2S-carboxamide underwent a highly regioselective and enantiospecific ring-opening reaction to afford an almost quantitative yield of R-beta-[(benzyl)phenylamino]-alpha-bromopropanamide (C-2 attack) and R-alpha-[(benzyl)phenylamino]-beta-bromopropanamide (C-3 attack) in a 10.5:1 ratio. Further treatment of the resulting ring-opening products with an N-nucleophilic reagent such as amine and azide led to, through most probably the aziridinium intermediate, the formation of S-alpha-substituted-beta-[(benzyl)phenylamino]propanamides in good chemical yields with high enantiomeric purity.     

Iterative organometallic addition to chiral hydroxylated cyclic nitrones: highly stereoselective syntheses of alpha,alpha'- and alpha,alpha-substituted hydroxypyrrolidines

[reaction: see text]. Iteration of organometallic addition to chiral hydroxylated pyrroline N-oxides through an addition-oxidation-addition synthetic sequence allowed highly stereoselective double alkylation of pyrrolidine at C-2 or at C-2 and C-5 depending on the regioselectivity of the oxidation step. Application of this methodology has been exemplified by the synthesis of the all-substituted pyrrolidine alkaloid (-)-codonopsinine and of proline-type amino acid precursors possessing a quaternary stereogenic center, whose configuration can be controlled.     

Nonracemic Betti base as a new chiral auxiliary: application to total syntheses of enantiopure (2S,6R)-dihydropinidine and (2S,6R)-isosolenopsins

Total syntheses of enantiopure alkaloidal natural products (2S,6R)-dihydropinidine (as hydrochloride) and (2S,6R)-isosolenopsins (as hydrochlorides) were achieved in four steps and in 80-82% total yields by using a synthetic strategy of the formation-cleavage of 1,3-oxazinane. (S)-Betti base was proved to be an excellent chiral auxiliary and a novel Pd/C catalyzed N-debenzylation straightforward to amine hydrochloride was developed in the presence of CH2Cl2.     

A tandem Heck-carbocyclization/Suzuki-coupling approach to the stereoselective syntheses of asymmetric 3,3-(diarylmethylene)indolinones

[reaction: see text] An efficient and versatile method for stereoselective synthesis of (E)-3,3-(diarylmethylene)indolinones by a palladium-catalyzed tandem Heck-carbocyclization/Suzuki-coupling sequence is presented. Factors influencing yield and selectivity, namely catalyst, coordinating ligand, and solvent, are detailed.     

A convergent route to the CDEF-tetracycle of pectenotoxin-2

A convergent synthesis of the CDEF-tetracyclic region of pectenotoxin-2 (PTX-2) is described. The synthetic pathway derives from a head-to-tail union of 2 equiv of linalool to establish a stereodefined DEF-tricyclic aldehyde. Subsequent coupling with a "northern" fragment enolate, followed by a tandem Sharpless epoxidation/cyclization, delivers the C10-C26 polycyclic region of the natural product.     

Synthetic studies related to diketopyrrolopyrrole (DPP) pigments. Part 2: The use of esters in place of nitriles in standard DPP syntheses: Claisen-type acylations and furopyrrole intermediates

Ethyl 2-aryl-4,5-dihydro-5-oxopyrrole-3-carboxylates react with esters or acyl halides in the presence of a strong base to give 4-acyl derivatives, which exist predominantly as either E- or Z-enols. These are cyclised, either in solution at temperatures >200 °C or by microwave irradiation, to 3,6-disubstituted 1H-furo[3,4-c]pyrrolediones which, after N-protection, are convertible by reaction with primary amines into novel N,N′-disubstituted DPP derivatives.