The Johnson Synthesis of Zaragozic Acid C

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Aldol Condensation ◽  
Enantiomerically Pure ◽  
Secondary Hydroxyl ◽  
Zaragozic Acids ◽  
Single Diastereomer ◽  
Stereogenic Centers ◽  
Aldol Cyclization ◽  
One Step ◽  
Zaragozic Acid ◽  
Zaragozic Acid C

The zaragozic acids, exemplified by Zaragozic Acid C 3, are picomolar inhibitors of cholesterol biosynthesis. Jeffrey S. Johnson of the University of North Carolina developed (J. Am. Chem. Soc. 2008, 130, 17281) an audacious silyl glyoxylate cascade approach to the oxygenated backbone fragment 1. Intramolecular aldol cyclization converted 1 to 2, setting the stage for the construction of 3. The lactone 2 includes five stereogenic centers, two of which are quaternary. The authors were pleased to observe that exposure of 4 to vinyl magnesium bromide 5 led, via condensation, silyl transfer, condensation, and again silyl transfer, to a species that was trapped with t-butyl glyoxylate 6 to give 7 as a single diastereomer. This one step assembled three of the stereogenic centers of 2, including both of the quaternary centers. The alcohol 7 so prepared was racemic, so the wrong enantiomer was separated by selective oxidation. Intramolecular aldol condensation of the derived α-benzyloxy acetate 1 then completed the construction of 2. Addition of the alkyl lithium 8, again as a single enantiomerically-pure diasteromer, to 2 gave the hemiketal 9. Exposure of 9 to acid initially gave a mixture of products, but this could be induced to converge to the tricyclic ester 10. To convert 10 to 11 , the diastereomer that was needed for the synthesis, two of the stereogenic centers had to be inverted. This was accomplished by exposure to t-BuOK/t-amyl alcohol, followed by re-esterification. The inversion of the secondary hydroxyl group was thought to proceed by retro-aldol/re-aldol condensation. Debenzylation of 11 followed by acetylation delivered 12, an intermediate in the Carreira synthesis of the zaragozic acids. Following that precedent, the ring acetates of 12 were selectively removed, leaving the acetate on the side chain. Boc protection was selective for the endo ring secondary hydroxyl, leaving the exo ring secondary hydroxyl available for condensation with the enantiomerically-pure acid 13. Global deprotection then completed the synthesis of Zaragozic Acid C 3. The key to the success of this synthesis of the complex spiroketal 3 was the assembly of 7 in one step as a single diastereomer from the readily-available building blocks 4, 5, and 6.

Enantioselective Organocatalyzed Construction of Carbocyclic Rings

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Michael Addition ◽  
Max Planck ◽  
Enantiomerically Pure ◽  
Single Diastereomer ◽  
Stereogenic Centers ◽  
Aldol Cyclization ◽  
National University ◽  
Carbocyclic Rings ◽  
Asymmetric Transformation ◽  
Technological University

One of the most practical ways to construct enantiomerically-enriched carbocyclic systems is to effect asymmetric transformation of preformed prochiral rings. Choon-Hong Tan of the National University of Singapore observed (Chem. Commun. 2008, 5526) that allylic halides such as 1 coupled with malonates such as 2 to give the α-methylene ketone 3 in high ee. Xinmiao Liang of the Dalian Institute of Chemical Physics and Jinxing Ye of the East China University of Science and Technology reported (Chem. Commun. 2008, 3302) that nitromethane 5 could be added to enones such as 4 to construct cyclic quaternary stereogenic centers such as that of 6. The addition of the cyclohexanone 7 to the acceptor 8 described (Chem. Commun. 2008, 6315) by Yixin Lu, also of the National University of Singapore led to the creation of two new cyclic stereogenic centers. Polycarbocyclic prochiral rings are also of interest. Teck-Peng Loh of Nanyang Technological University devised (Tetrahedron Lett. 2008, 49, 5389) the steroid AB donor 10, that added to crotonaldehyde 1 to give the single enantiomerically-pure diastereomer 12. Nitro alkenes are excellent Michael acceptors. Dieter Enders of RWTH Aachen took advantage of this (Angew. Chem. Int. Ed. 2008, 47, 7539) in developing the addition of aldehydes such as 14 to the nitroalkene 13. Intramolecular alkylation ensued, to deliver the product 15 as a single diastereomer. Guofu Zhong, also of Nanyang Technological University, established (Organic Lett. 2008, 10, 3425; Organic Lett. 2008, 10, 3489) an approach to cyclopentane construction based on the Michael addition of β-ketoesters such as 16 and 19 to nitroalkenes such as 17 and 20. Intramolecular nitro aldol (Henry) addition led to 18, while an intramolecular Michael addition delivered 21. Damien Bonne and Jean Rodriguez of Aix-Marseille Université employed (Organic Lett. 2008, 10, 5409) intramolecular dipolar cycloaddition to convert the initial adduct between 22 and 23 to the cyclopentane 24. They also prepared cyclohexane derivatives using this approach. The diketone 25 is prochiral. Benjamin List of the Max-Planck Institut, Mülheim devised (Angew. Chem. Int. Ed. 2008, 47, 7656) an organocatalyst that mediated the intramolecular aldol cyclization of 25 to 26 in high ee.

Studies towards the synthesis of the zaragozic acids: Synthesis of the bicyclic acetal core of zaragozic acid C

1997 ◽  
Vol 38 (24) ◽  
pp. 4301-4304 ◽  
Author(s):  
Ian Paterson ◽  
Klaus Feßner ◽  
M.Raymond V. Finlay
Keyword(s):  
Zaragozic Acids ◽  
Zaragozic Acid ◽  
Zaragozic Acid C

Stereocontrolled Construction of Arrays of Stereogenic Centers

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Aldol Condensation ◽  
Simple Procedure ◽  
Unsaturated Ester ◽  
Magnesium Bromide ◽  
National Chemical Laboratory ◽  
Chemical Laboratory ◽  
Enantiomerically Pure ◽  
Stereogenic Centers ◽  
Diastereoselective Addition ◽  
The University

Complex natural products and even some complex pharmaceuticals contain arrays of stereogenic centers. Sometimes, the desired array is readily available from a natural product, but usually, such arrays of multiple stereogenic centers must be assembled. Armando Córdova of Stockholm University has reported (Angew. Chem. Int. Ed. 2007, 46, 778) a simple procedure for the organocatalyst-mediated addition of the nitrene equivalent 2 to an α, β-unsaturated aldehyde to give the protected aziridine 4 in high ee. Organocatalysis was also used (Organic Lett. 2007, 9, 1001) by Arumugam Sudalai of the National Chemical Laboratory, Pune, to effect coupling of the aldehyde 5 with dibenzylazodicarboxylate 6 to give, following the List procedure, the intermediate aldehyde 7. Osmylation of the derived unsaturated ester 8 proceeded with high diastereocontrol, to give 9. Products 4 and 9 have adjacent stereogenic centers. Hisashi Yamamoto of the University of Chicago has introduced (J. Am. Chem. Soc. 2007, 129, 2762) the linchpin reagent acetaldehyde “super”silyl enol ether 11. Diastereoselective addition of 11 to the enantiomerically-pure aldehyde 10, with concomitant silyl transfer, followed by the addition of allyl magnesium bromide delivered the protected triol 12 in high de and ee. Arrays that combine alkylated and oxygenated or aminated centers are also important. Akio Kamimura of Yamaguchi University took (J. Org. Chem. 2007, 72, 3569) a Baylis- Hillman like approach, adding thiophenoxide to t -butyl acrylate in the presence of an enantiomerically-pure aldehyde N-sulfinimine such as 13 to give the adduct 14 with high diastereocontrol. Keiji Maruoka of Kyoto University has designed (Angew. Chem. Int. Ed. 2007, 46, 1738) the chiral amine 17, that catalyzed the condensation of an aldehyde with ethyl glyoxylate 16 with high enantiocontrol. In a very thoughtful approach, Liu-Zhu Gong of the University of Science and Technology of China in Hefei extended (Chem. Commun. 2007, 736) the now-classic aldol condensation of cyclohexanone to 4-substituted cyclohexanones such as 19. The product 21 could be carried in many directions, including to the Bayer-Villiger product 22. Arrays of alkylated and polyalkylated centers have been among the most challenging to prepare.

The asymmetric syntheses of the C-1 sidechains of zaragozic acid A and zaragozic acid C

1993 ◽  
Vol 34 (52) ◽  
pp. 8403-8406 ◽  
Author(s):  
Albert J. Robichaud ◽  
Gregory D. Berger ◽  
David A. Evans
Keyword(s):  
Asymmetric Syntheses ◽  
Zaragozic Acid ◽  
Zaragozic Acid C

Total Synthesis of the Squalene Synthase Inhibitor Zaragozic Acid C by a Carbonyl Ylide Cycloaddition Strategy

2003 ◽  
Vol 115 (43) ◽  
pp. 5509-5513 ◽  
Author(s):  
Seiichi Nakamura ◽  
Yuuki Hirata ◽  
Takahiro Kurosaki ◽  
Masahiro Anada ◽  
Osamu Kataoka ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Squalene Synthase ◽  
Carbonyl Ylide ◽  
Zaragozic Acid ◽  
Synthase Inhibitor ◽  
Squalene Synthase Inhibitor ◽  
Zaragozic Acid C

scholarly journals New palladium–oxazoline complexes: Synthesis and evaluation of the optical properties and the catalytic power during the oxidation of textile dyes

2015 ◽  
Vol 11 ◽  
pp. 1175-1186 ◽  
Author(s):  
Rym Hassani ◽  
Mahjoub Jabli ◽  
Yakdhane Kacem ◽  
Jérôme Marrot ◽  
Damien Prim ◽  
...  
Keyword(s):  
Optical Properties ◽  
Spectroscopic Analysis ◽  
Palladium Complexes ◽  
X Ray Diffraction ◽  
Factors Affecting ◽  
Enantiomerically Pure ◽  
One Step ◽  
Uv Visible ◽  
High Yields

The present paper describes the synthesis of new palladium–oxazoline complexes in one step with good to high yields (68–95%). The oxazolines were prepared from enantiomerically pure α-aminoalcohols. The structures of the synthesized palladium complexes were confirmed by NMR, FTIR, TOFMS, UV–visible spectroscopic analysis and X–ray diffraction. The optical properties of the complexes were evaluated by the determination of the gap energy values (E g) ranging between 2.34 and 3.21 eV. Their catalytic activities were tested for the degradation of Eriochrome Blue Black B (a model of azo dyes) in the presence of an ecological oxidant (H2O2). The efficiency of the decolorization has been confirmed via UV–visible spectroscopic analysis and the factors affecting the degradation phenomenon have been studied. The removal of the Eriochrome reached high yields. We have found that the complex 9 promoted 84% of color elimination within 5 min (C 0 = 30 mg/L, T = 22 °C, pH 7, H2O2 = 0.5 mL) and the energetic parameters have been also determined.

Enzymes in organic synthesis. 32. Stereospecific horse liver alcohol dehydrogenase-catalyzed oxidations of exo- and endo-oxabicyclic meso diols

1984 ◽  
Vol 62 (11) ◽  
pp. 2578-2582 ◽  
Author(s):  
J. Bryan Jones ◽  
Christopher J. Francis
Keyword(s):  
Alcohol Dehydrogenase ◽  
Organic Synthesis ◽  
Horse Liver Alcohol Dehydrogenase ◽  
Preparative Scale ◽  
Enantiomerically Pure ◽  
Liver Alcohol Dehydrogenase ◽  
Horse Liver ◽  
One Step ◽  
Catalyzed Oxidation ◽  
Enzymes In Organic Synthesis

Preparative-scale horse liver alcohol dehydrogenase-catalyzed oxidation of mesoexo- and endo-7-oxabicyclo[2.2.1]heptane diols provides a direct one-step route to enantiomerically pure chiral γ-lactones of the oxabicyclic series.

The Roush Synthesis of ( + )-Superstolide A

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Malignant Cell ◽  
Alder Reaction ◽  
Diels Alder ◽  
Protecting Group ◽  
The Third ◽  
Diels Alder Reaction ◽  
Single Diastereomer ◽  
Superstolide A ◽  
One Step ◽  
Fourth Component

( + )-Superstolide A 3, isolated from the New Caledonian sponge Neosiphonia superstes, shows interesting cytotoxicity against malignant cell lines at ~ 4 ng/mL concentration. The key transformation in the synthesis of 3 described (J. Am. Chem. Soc. 2008, 130, 2722) by William R. Roush of Scripps Florida was the transannular Diels-Alder cyclization of 2, which established, in one step with high diastereocontrol, both the cis decalin and the macrolactone of 3. The octaene 1 was assembled from four stereodefined fragments. The first, the linchpin 6, was prepared from the stannyl aldehyde 4. Homologation gave the enyne 5, which on hydroboration and oxidation gave 6. Earlier, Professor Roush had optimized the crotylation of the protected alaninal 7. In this case, the Brown reagent 8 delivered the desired Felkin product 9. Protection followed by ozonolysis gave the aldehyde 10. Crotylation with the Roush-developed tartrate 11 then gave the alkene 12, setting the stage for conversion to the iodide 13. Coupling of 13 with 6 completed the preparation of 14. The third component of (+)-superstolide A 3, the phosphonium salt 21, was assembled by Brown allylation of the aldehyde 15, to give 17. Protecting group interchange followed by ozonolysis delivered 18, which via Still-Gennari homologation was carried on to 21. Condensation with the fourth component, the aldehyde 22 , and esterification with 14 then gave 1. Under high dilution Suzuki conditions 1 was converted to 2. Storage in CDCl3 for five days, or brief warming, cyclized 2 to a single diastereomer of the transannular Diels-Alder product, that was carried on to (+)-superstolide A 3. While acyclic trienes comparable to 2 could be induced to cyclize, the transannular Diels-Alder reaction proceeded with much higher diastereocontrol.

Enantioselective Organocatalytic Construction of Carbocycles: The Nicolaou Synthesis of Biyouyanagin A

2011 ◽  
Author(s):  
Douglass Taber
Keyword(s):  
Methyl Ether ◽  
Conjugate Addition ◽  
Unsaturated Aldehyde ◽  
Enantiomerically Pure ◽  
Intramolecular Alkylation ◽  
Stereogenic Centers ◽  
Chinese Academy Of Sciences ◽  
Academy Of Sciences ◽  
Polycyclic System ◽  
Selective Addition

One of the more powerful routes to enantiomerically-pure carbocycles is the desymmetrization of a prochiral ring. Karl Anker Jørgensen of Aarhus University has found (J. Am. Chem. Soc. 2007, 129, 441) that many cyclic β-ketoesters, including the vinylogous carbonate 1, can be homologated with 2 to the corresponding alkyne 3, in high ee. Sanzhong Luo of the Chinese Academy of Sciences, Beijing, and Jin-Pei Cheng, of the Chinese Academy of Sciences and Nankai University, have shown (J. Org. Chem. 2007, 72, 9350) that the catalyst 6 mediated the selective addition of 4-substituted cyclohexanones such as 4 to the nitroalkene 5, establishing three new stereogenic centers. Organocatalysts, alone or complexed with activating metals, have also been used to effect enantioselective ring construction. E. J. Corey of Harvard University has established (J. Am. Chem. Soc. 2007, 129, 12686) that the proline-derived complex 10 will mediate the 2 + 2 addition of a cyclic enol ether with an acrylate to give the cyclobutane 11. Further elaboration led to the cyclohexenone 12. Armando Córdova of Stockholm University has described (Tetrahedron Lett. 2007, 48, 5835) a novel route to cyclopentanones such as 16, via tandem conjugate addition/intramolecular alkylation. Professor Jørgensen has reported (Angew. Chem. Int. Ed . 2007, 46 , 9202) the double addition of 18 to the unsaturated aldehyde 17 to give 20. Earlier last year, Yujiro Hayashi of the Tokyo University of Science had shown (Angew. Chem. Int. Ed. 2007, 46, 4922) that the double addition of the inexpensive 21 to 5 could, depending on conditions, be directed selectively to 22, 23, or 24. As illustrated by the conversion of 8 to 13, organocatalysis can be used to effect the enantioselective construction of polycarbocyclic products. The initial ring prepared in enantiomerically-pure form by organocatalysis can also set the chirality of a polycyclic system. Professor Corey has reported (J. Am. Chem. Soc. 2007, 129, 10346) that Itsuno-Corey reduction of the prochiral diketone 25 led to the ketone 27. Cyclization followed by oxidation and reduction then delivered estrone methyl ether 28.

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