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IRIDOIDS : ENANTIOSELECTIVE SYNTHESIS OF LOGANIN VIA AN ASYMMETRIC DIELS-ALDER REACTION

Starting from (-)-camphor-10-sulfonic acid (5) the crystalline sultam 9 was readily prepared.TiCl4-mediated Diels-Alder addition of the N-crotonyl sultam 11 to cyclopentadiene, crystallization of the resulrting adduct 12 and subsequent reduction gave virtually pure (1S, 4R,5R, 6S)-1 together with recovered auxiliary 9.The loganin precursor 1 was transformed into norbonanone 20, which upon Baeyer-Villiger oxidation led to the suitably substituted cyclopentane 22 from which 1-B-O-methyl loganin aglucone (2) was readily available.

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Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

 

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Novel application of chiral micellar media to the Diels-Alder reaction

A novel chiral surfactant has been used in the first reported aqueous chiral micellar catalysis of a Diels-Alder reaction and enantioselectivities have been observed.

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Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

 

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Progress toward the total synthesis of callipeltin A (I): Asymmetric synthesis of (3S,4R)-3,4-dimethylglutamine

(equation presented) During the total synthesis of the novel cyclic depsipeptide callipeltin A (1), the unit (3S,4R)-3,4-dimethylglutamine, was successfully synthesized by asymmetric Michael addition and subsequent electrophilic azidation. The key feature of this approach is the generation of three adjacent stereogenic centers using the same camphorsultam chiral auxiliary.

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Reference£º
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

 

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Process for the preparation of substituted pyrrolidine derivatives and intermediates

Two syntheses are provided; one for the preparation of (3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol, and other for the preparation of (3S,4R)-4-(hydroxymethyl)pyrrolidin-3-ol. (3R,4R)-4-(hydroxymethyl)pyrrolidin-3-ol is prepared using the achiral ylide prepared from benzylamine instead of phenethylamine (Scheme 3) which provides a crystalline intermediate. The synthesis of (3S,4R)-4-(hydroxymethyl)pyrrolidin-3-ol is achieved from (S)-diethylmalate as described in Scheme 4. A process for preparing camphor sultam is also provided.

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Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

 

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Asymmetric Oxidation of Ester and Amide Enolates Using New (Camphorylsulfonyl)oxaziridines

The first asymmetric oxidation of ester and amide lithium enolates 5 to optically active alpha-hydroxycarbonyl compounds 6 is reported using new, easily prepared, stable (camphorylsulfonyl)oxaziridines (+)-(2R,8aS)-3 and (-)-(2S,8aR)-4.Either enantiomer of 6 can be readily obtained because the configuration of the oxaziridine three-membered ring determines the product stereochemistry.

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Isothiazole – Wikipedia,
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Methods and systems for evaluating and predicting the reactivity of monooxygenase enzymes

Methods and systems for evaluating and predicting the reactivity of natural and engineered monooxygenase enzymes are provided. Methods are provided for acquiring a functional profile (fingerprint) of monooxygenases that encode information regarding the active site configuration of such monooxygenases. Methods are also provided for carrying out analysis of a monooxygenase fingerprint, to formulate predictions regarding the reactivity properties (e.g., substrate reactivity, chemo-, regio, and stereoselectivity properties) of the fingerprinted monooxygenases.

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Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

 

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Chemistry of Oxaziridines. 18. Synthesis and Enantioselective Oxidations of the <(8,8-Dihalocamphoryl)sulfonyl>oxaziridines

The synthesis and enantioselective oxidations of <(8,8-dihalocamphoryl)sulfonyl>oxaziridines 13 are reported.These reagents are prepared in two steps from the (camphorylsulfonyl)imine 4 by treatment of the corresponding azaenolate with electrophilic halogen sources followed by biphasic oxidation of the resulting dihalo imine 6-9 with m-CPBA/K2CO3.Of these oxaziridines the dichloro reagent 13b, available on a multigram scale, affords the highest enantioselectivities for the asymmetric oxidation of sulfides to sulfoxides (42-74 percent) and for the hydroxylation of enolates (often better than 95 percent ee).In general the molecular recognition is predicted and explained in terms of minimization of nonbonded steric interactions in the transition states.For the asymmetric oxidation of sulfides to sulfoxides, secondary electronic factors related to the polarity of the sulfide and oxaziridine also play a role.Definitive evidence for chelation of the metal enolate with the C-X bond in 13 is not found.The molecular recognition is interpreted in terms of the higher reactivity of the reagents and an active-site structure which is sterically complementary with the enolate.For the asymmetric hydroxylation of the Z- and E-enolates of propiophenone (16a), the Z-enolate exhibits much higher stereoselectivity than the E-enolate: >95 percent vs 22 percent ee.

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Isothiazole – Wikipedia,
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Asymmetric synthesis of sultams and sulfonamides via diastereoselective reduction of N-sulfonylimines

The diastereoselective reduction of both cyclic and acyclic camphor sulfonylimines was investigated. With cyclic camphor sulfonylimines 1, reduction using NaBH4 in methanol afforded the corresponding camphorsultams 2 in 92-95% yield as single diastereomers with the exception of 1c where debromination occurred prior to reduction. For the large scale preparation of camphorsultam 1a and its derivatives, important chiral auxiliaries in asymmetric synthesis, reduction with NaBH4 is the reagent of choice. Reduction of acyclic camphor sulfonylimines 7 to camphorsulfonamides 8 with the bulky reducing reagent, LiAl(OBu-i)3H afforded the highest de’s (>90% de) and yields 90-95%.

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Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

 

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Metal-Free Synthesis of the Methanol Solvate of (S)-Omeprazole Potassium Salt Using (1 R)-(-)-10-Camphorsulfonyloxaziridine: Oxidation Process Development and Optical Purity Enhancement Strategy

The results of our process development studies to synthesize the methanol solvate of (S)-omeprazole potassium salt (1) through the enantioselective oxidation of pyrmetazole (2) using (1R)-(-)-10-camphorsulfonyloxaziridine (3) are reported. Optical purity enhancement was achieved by means of a reslurry from methanol, the rationale and development details of which are also described.

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Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com

 

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A convenient, improved synthesis of (camphoryl)sulfonyl oxaziridines

A convenient, efficient procedure for the large scale synthesis of chiral oxidizing reagents (+), and (-)-((8,8-dichlorocamphory)sulfonyl)oxaziridine, 5, as well as of 8,8 unsubstituted (+), and (-) (camphoryl)sulfonyl oxaziridine, 4, from (+), or (-) (camphoryl)imine, 2, in step yields of 83% to 95%, is reported.

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Reference£º
Isothiazole – Wikipedia,
Isothiazole – ScienceDirect.com