Catalytic asymmetric epoxidation and kinetic resolution: modified procedures including in situ derivatization

Gao, Yun; Hanson, Robert M.; Klunder, Janice M.; Ko, Soo‐Byung; Masamune, Hiroko; Sharpless, K. Barry

doi:10.1021/ja00253a032

Cited by 2,010 publications

(949 citation statements)

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“…Asymmetric epoxidation [33] of geraniol afforded (2S,3S)-2,3-epoxygeraniol (20a, 94:4 er), and the 2R,3R-antipode (ent-20a). The enantiomeric purities were established by conversion to the diasteromeric (S)-camphanate ester ((S)-camphanic chloride, DMAP, pyr, 2h) [34] and 1 H NMR analysis in DMSO-d 6 .…”

Section: Phosphorylation Of 2-fluorolinaloolmentioning

confidence: 99%

Inhibition of monoterpene cyclases by inert analogues of geranyl diphosphate and linalyl diphosphate

Karp

Zhao

Santhamma

et al. 2007

Archives of Biochemistry and Biophysics

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The tightly coupled nature of the reaction sequence catalyzed by monoterpene synthases has prevented direct observation of the topologically required isomerization step leading from geranyl diphosphate to the enzyme-bound, tertiary allylic intermediate linalyl diphosphate, which then cyclizes to the various monoterpene skeletons. X-ray crystal structures of these enzymes complexed with suitable analogues of the substrate and intermediate could provide a clearer view of this universal, but cryptic, step of monoterpenoid cyclase catalysis. Toward this end, the functionally inert analogues 2-fluorogeranyl diphosphate, (±)-2-fluorolinalyl diphosphate, and (3R)-and (3S)-homolinalyl diphosphates (2,6-dimethyl-2-vinyl-5-heptenyl diphosphates) were prepared, and compared to the previously described substrate analogue 3-azageranyl diphosphate (3-aza-2,3-dihydrogeranyl diphosphate) as inhibitors and potential crystallization aids with two representative monoterpenoid cyclases, (−)-limonene synthase and (+)-bornyl diphosphate synthase. Although these enantioselective synthases readily distinguished between (3R)-and (3S)-homolinalyl diphosphates, both of which were more effective inhibitors than was 3-azageranyl diphosphate, the fluorinated analogues proved to be the most potent competitive inhibitors and have recently yielded informative liganded structures with limonene synthase.

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Section: Phosphorylation Of 2-fluorolinaloolmentioning

confidence: 99%

Inhibition of monoterpene cyclases by inert analogues of geranyl diphosphate and linalyl diphosphate

Karp

Zhao

Santhamma

et al. 2007

Archives of Biochemistry and Biophysics

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“…[16][17][18][19] Enantioenriched allylic alcohols are often isolated from kinetic resolution (KR) with the Sharpless-Katsuki asymmetric epoxidation catalyst. [5][6][7]4 Although (E)-allylic alcohols are excellent substrates for the KR, (Z)-disubstituted allylic alcohols are not (Scheme 1). [5][6][7]4 Other drawbacks to the KR include the need to separate the desired allylic alcohol from the epoxy alcohol product and a maximum yield of 50%.…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7]4 Although (E)-allylic alcohols are excellent substrates for the KR, (Z)-disubstituted allylic alcohols are not (Scheme 1). [5][6][7]4 Other drawbacks to the KR include the need to separate the desired allylic alcohol from the epoxy alcohol product and a maximum yield of 50%. 20 More efficient methods to prepare allylic alcohols include asymmetric vinylation of aldehydes [21][22][23][24][25]13,15,[8][9][10][26][27][28] or ketones 29,30 (Scheme 2) and reductive coupling of alkynes and carbonyl compounds.…”

Section: Introductionmentioning

confidence: 99%

Catalytic Asymmetric Generation of (Z)-Disubstituted Allylic Alcohols

et al. 2007

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A one-pot method for the direct preparation of enantioenriched (Z)-disubstituted allylic alcohols is introduced. Hydroboration of 1-halo-1-alkynes with dicyclohexylborane, reaction with t-BuLi, and transmetallation with dialkylzinc reagents generates (Z)-disubstituted vinylzinc intermediates. In situ reaction of these reagents with aldehydes in the presence of a catalyst derived from (−)-MIB generates (Z)-disubstituted allylic alcohols. It was found that the resulting allylic alcohols were racemic, most likely due to a rapid addition reaction promoted by LiX (X = Br and Cl). To suppress the LiX promoted reaction, a series of inhibitors was screened. It was found that 20-30 mol % tetraethylethylene diamine (TEEDA) inhibited LiCl without inhibiting the chiral zinc-based Lewis acid. In this fashion, (Z)-disubstituted allylic alcohols were obtained with up to 98% ee. The asymmetric (Z)-vinylation could be coupled with tandem diastereoselective epoxidation reactions to provide epoxy alcohols and allylic epoxy alcohols with up to three contiguous stereogenic centers, enabling the rapid construction of complex building blocks with high levels of enantio-and diastereoselectivity.

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“…Chart 5 summarizes the synthesis of alkyne 57, 44) starting with the known allyl alcohol 52. 45) Catalytic asymmetric epoxidation of 52 under Sharpless conditions 46) provided epoxy alcohol 53 in 91% yield and 92% ee. Enantiomeric excess could be enhanced to 100% upon recrystallization of the derived 3,5-dinitrobenzoate 54.…”

Section: The Aldol Approach To Zaragozic Acid Cmentioning

confidence: 99%

Total Synthesis of the Squalene Synthase Inhibitor Zaragozic Acid C

Nakamura

2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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Zaragozic acids and squalestatins were documented by Merck, Glaxo, and Tokyo Noko University/Mitsubishi Kasei Corporation as part of a program aimed at identifying novel inhibitors of squalene synthase, as well as farnesyl transferase. These natural products have attracted considerable attention from numerous synthetic chemists because of their therapeutic potential and novel architecture. This review highlights our total syntheses of zaragozic acid C by two convergent strategies. The key steps in our first-generation synthesis involve 1) simultaneous creation of the C4 and C5 quaternary stereocenters through the Sn(OTf) 2 -promoted aldol coupling reaction between the a a-keto ester and silyl ketene thioacetal derived from L-and D-tartaric acids, respectively; and 2) construction of the bicyclic core structure via acid-catalyzed internal ketalization under kinetically controlled conditions. The second-generation strategy relies on a tandem carbonyl ylide formation/1,3-dipolar cycloaddition approach and features elongation of the C1 alkyl side chain through an olefin cross-metathesis as well as high convergency and flexibility.

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Catalytic asymmetric epoxidation and kinetic resolution: modified procedures including in situ derivatization

Cited by 2,010 publications

References 0 publications

Inhibition of monoterpene cyclases by inert analogues of geranyl diphosphate and linalyl diphosphate

Inhibition of monoterpene cyclases by inert analogues of geranyl diphosphate and linalyl diphosphate

Catalytic Asymmetric Generation of (Z)-Disubstituted Allylic Alcohols

Total Synthesis of the Squalene Synthase Inhibitor Zaragozic Acid C

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