The chemistry of thujone. VI. Thujone as a chiral synthon for the synthesis of optically active steroid analogues

The thujone derived enone 1 is converted in one step to the pentacyclic compound 4 . The structure of 4 was determined by X-ray diffraction analysis. The acid-catalyzed cyclopropane-ring opening of 4 and of the model compound 9 are described.     

The chemistry of thujone. VIII. Thujone as a chiral synthon for the synthesis of optically active steroid analogues. The enol lactone route

The thujone-derived enone 1 is converted via enol lactone intermediates 4 and 5 to the optically active steroidal analogue 13 and the corresponding 19-norsteroid analogue 14 . The structure of 13 was determined by X-ray diffraction analysis. The acid-catalyzed cyclopropane-ring opening of 13 and ozonolysis of the resulting olefin provided the 16-keto-steroid analogue 18 .     

Chemoenzymatic synthesis of (R)-(+)-2-methylbutan-1-ol,a chiral synthon for the preparation of optically active pheromones

Optically active (R)-(+)-2-methylbutan-1-ol (which is not commercially available) was prepared by a chemoenzymatic synthesis, in which the key step involved a reduction catalyzed by baker's yeast. The synthon was used in the synthesis of (R)-10-methyldodecan-1-yl acetate, the chiral methyl-branched pheromone of Adoxophyes sp.     

New synthesis of a chiral steroid cd-ring synthon by means of enantioselective double Michael addition

A new synthetic method of (+)-(1R)-acetyl-(7aR)-methyl-4-hydroinden-5-one (2) by highly enantioselective double Michael addition involving alkenylcopper-phosphine complex, 3-trimethylsilylbutenone and 2-methyl-2-cyclo-pentenone is presented.     

Highly enantioselective synthesis of optically active hydroxyaldehydes using a chiral catalyst

Optically active hydroxyaldehydes arc synthesized in 88–94% e.e. by the catalytic enantioselective addition of dialkylzinc using N,N-dibutylnorephedrine.     

A new convenient route to enantiopure 2-coumarinyloxypropanals: application to the synthesis of optically active geiparvarin analogues

A new convenient route to enantiopure 2-coumarinyloxypropanals is described: Rosenmund reduction of (R)- or (S)-2-coumarinyloxypropanoyl chlorides afforded in good yields the corresponding 2-coumarinyloxypropanals. Their subsequent aldolic condensation with 3(2H)-furanones, followed by dehydration, led to enantiopure geiparvarin analogues now being investigated as promising antitumoral compounds.     

The Chemistry of Thujone. Part XIV.. Synthesis of biologically active aryl terpenoid analogues

Employing thujone-derived intermediates, a series of achiral ( 9a–d ; Scheme 1) and chiral ( 11b and 11d; Scheme 2) terpene analogues related to the biologically active ‘terpenoid’ hybrids have been prepared. The stereochemistry of the key epoxidation reaction was established by correlation of the product 11b with the previously reported alcohol (R)- 20 of known absolute configuration (Scheme 3).     

Radical-mediated diastereoselective construction of a chiral synthon for synthesis of dolabellanes

[reaction: see text] A useful trans-substituted multifunctional cyclopentane with a chiral quaternary center was selectively synthesized by free radical Michael addition to the (Z)-propionate or -malonate derivatives. The stereoselectivity could be reversed by changing the configuration of the double bond.     

Ketones as a new synthon for quinoxaline synthesis

o-Phenylenediamines react with an array of ketones in PEG-400 at 60 °C under an atmosphere of air in the presence of KOH to afford the corresponding quinoxalines in good yields.     

2-Carbomethoxycyclopentenone as a synthon. synthesis of sarkomycin

The first regiospecific synthesis of sarkomycin (II), a compound active against ascites-type tumors, is reported. Treatment of 2-carbomythoxycyclopentenone (I) with Et₂AlCN generated the carbon skeleton; aelective functional group manipulations then gave the keto lactone X and the protected hydroxy acid XI; and mild acid treatment of these led to sarkomycin.     

Esterase-mediated synthesis of optically active GABA analogues containing a stereogenic all-carbon quaternary carbon atom

Esterase from Horse Liver (HLAP) was able to hydrolyze a series of linear and cyclic β,β-dialkyl-γ-nitroesters, in spite of the well-known reluctance of hydrolytic enzymes to recognize and transform hindered substrates, such as those possessing a stereogenic quaternary carbon atom next to the reaction site. The resulting optically active γ-nitroesters gave access to optically active β,β-disubstituted γ-aminoacids as well as α,α-disubstituted succinic acids, both being biologically relevant compounds.     

Recent advances of optically active helical polymers as adsorbents and chiral stationary phases for chiral resolution

Chiral resolution is very important and still a big challenge due to different biological activity and same physicochemical property of one pair (R)- and (S)-isomer. There is no doubt that chiral selectors are essentially needed for chiral resolution, which can stereoselectively interact with a pair of isomers. To date, a large amount of optically active helical polymers as chiral selectors have been synthesized via two strategies. First, the target helical polymers are derived from natural polysaccharide such as cellulose and amylose. Second, they can be synthesized by polymerization of chiral monomers. Alternatively, an achiral polymer is prepared first followed by static or dynamic chiral induction. Furthermore, a part of them is harnessed as chiral stationary phases for chromatographic chiral separation and as chiral adsorbents for enantioselective adsorption/crystallization, resulting in good enantioseparation efficiency. In summary, the present review will focus on recent progress of the polymers with optical activity for chiral resolution, especially the literature published in the past 10 years. In addition, development prospects and future challenges of optically active helical polymers will be discussed in detail.     

Total synthesis of optically active liverwort sesquiterpenes,trifarienols A and B,using phenylethylamine as a chiral auxiliary

The imine of (rac)-2,3-dimethylcyclohexanone 10a with (S)-(−)-phenylethylamine was reacted with methyl acrylate to yield methyl (1′S,6′R)-3-(1′,6′-dimethyl-2′-oxocyclohexyl)propanoate 4a in 26% (97% ee) after hydrolysis. When (2RS,3R)-2,3-dimethylcyclohexanone 10b was used, the same product 4b was obtained in 59% yield (>99.5% ee) after hydrolysis. When (2RS,3R)-2,3-dimethylcyclohexanone 10b and (R)-(+)-phenylethylamine were used, the reaction underwent in only 5% yield, the products being 4c, 12, 13, 14, and 15. Thus, the reaction of 3b with methyl acrylate is a matched case, while that of 3c is a mismatched case. These phenomena are explained by the nonbonded interaction of methyl acrylate with chiral phenylethylamine and the methyl group at the 6′-position of the cyclohexanone ring in the transition state. The propanoate product 4b was successfully transformed into liverwort sesquiterpene (+)-trifarienol A 1 and (−)-trifarienol B 2 in 10 steps. We have developed an HPLC method to determine the ees of 2,2-disubstituted and 2,2,3-trisubstituted cyclohexanones using the corresponding pentafluorophenyl esters.     

New chiral binaphthyl building blocks: synthesis of the first optically active tetrathiafulvalene dimers

New enantiomerically pure binaphthyl derivatives bearing triphenylphosphine or phosphonate groups have been synthesized and used as building blocks to prepare the first optically active tetrathiafulvalene dimers.     

Click chemistry as a route to cyclic tetrapeptide analogues: synthesis of cyclo-[Pro-Val-psi(triazole)-Pro-Tyr

[STRUCTURE: SEE TEXT] Despite the plethora of techniques to cyclize small peptides, a synthesis of cyclo-[(L)Pro-(L)Tyr-(L)Pro-(L)Val], a potent tyrosinase inhibitor, remains elusive because of the unfavorable transition state leading to the cyclic product. Herein, we report the successful synthesis of its triazole analogue, cyclo-[(L)Pro-(L)Val-psi(triazole)-(L)Pro-(L)Tyr]. Attempted cyclization via peptide bond formation at room temperature fails to provide the desired product, but Cu(I)-catalyzed alkyne-azide coupling at 110 degrees C affords the triazole tetrapeptide in 70% yield, demonstrating the utility of "click" chemistry.     

A new strategy for the synthesis of optically active benzylic fluorides and corresponding five-membered heteroaromatic analogues

Benzylic fluorides, as well as five-membered heterocycles, have been obtained in high ee’s through cycloaddition reactions starting from easily accessible optically active propargylic fluorides.     

A chiral pool approach to the synthesis of optically active tetrahalo norbornyl building blocks

Optical antipodes of the mono- and disubstituted polyhalo norbornyl derivatives were prepared in excellent yields. The monosubstituted derivatives 7 were obtained with good enantiopurities. A kaleidoscopic change in the product formation and distribution was observed by changing the chronology of reactions.