Selective Epimerization Research Articles

Organofluorine compounds and fluorinating agents Part 17: Sonochemical-forced preparation of perfluoroalkanals and their use for non-conventional acetalations of carbohydrates

The homologous 1-iodo-perfluoroalkanes 1a-1c and α,ω-dibromo-perfluoroalkanes 4a, 4b were carbonylated with DMF in the presence of Al/SnCl 2 Al/PbBr 2 under sonication in a short reaction time. The hydrated aldehydes 2a-2c and 5a, 5b respectively were obtained in good yields allowing dehydration to 3a-3c and 6a, 6b. Some of the fluorinated aldehydes were selected as substrates in a Wittig-Horner olefination assisted by ultrasound and in non-conventional acetalations of methyl α- l-rhamnopyranoside ( 9). Thus, ( E)-1-perfluorooctyl-2-phenylsulphonyl-ethene ( 8) was prepared from 3c and the phosphonate 7 by Wittig-Horner synthesis. Acetalations of 9 were carried out with the aldehydes ( 3a, 3b, 6a), hydrated aldehydes ( 2a, 2b), and the aldehyde hemiacetal 12 respectively, in the presence of dicyclohexylcarbodiimide (DCC). In all cases, a selective epimerization was observed at the C-atom 3 of the monosaccharide, i.e. polyfluoroalkylidenated 6-deoxy-α- l-altropyranosides 10,11,13, and 14 were obtained.

Selective epimerization and skeletal resection in the ascomycin framework: A study of the biological consequences of lactam rotamer selection

Ascomycin ( 1a), a macrolactam antifungal antibiotic disclosed by Arai in 1962, 1 was found to display immunosuppressive activity more than 2 decades later by Okuhara and coworkers at Fujisawa. 2 Ascomycin ( 1a) and FK506 ( 1b) bind to a peptidyl-prolyl-isomerase, FKBP, a necessary but insufficient condition for drug activity. Both FK506 and ascomycin exist as a mixture of slowly interconverting cis and trans amide rotamers. It has also been shown that only the trans amide rotamer binds to FKBP. 24-epi-Ascomycin ( 3), 24-oxo-22-norascomyin ( 9a), and 22-norascomycin ( 9b), obtained by semisynthesis from ascomycin, exist as single rotamers on the NMR time scale. Their synthesis and the biological consequences of this observation are discussed.

Highly Selective Epimerization of the 3β-Hydroxyl Function of Gibberellin Derivatives with a Base in an Aprotic Medium: Efficient Preparation of Methyl Esters of3-epi-GA and3-epi-GA1

Methyl esters of 3-epi-GA3 and 3-epi-GA1 were efficiently prepared from methyl esters of GA3 and GA1 respectively, by highly selective epimerization of the 3-hydroxyl function with a base in a low-polar aprotic medium.

Stereoselective access to polyfunctionalized decalins

As a model of a stereoselective approach to ajugareptansin 1, a versatile and straightforward access to polyfunctionalized cis or trans decalins is presented. It is based on a Lewis acid-mediated addition of furan to the unsaturated ketoester 3 followed by oxidative opening of the furan to give cis decalins by an aldolisation process. Selective epimerization at carbons 5 or 10 is described and allows the access to the trans ring geometry.

Asymmetric synthesis of (–)-(1R,2S)-cispentacin and related cis- and trans-2-amino cyclopentane- and cyclohexane-1-carboxylic acids

The antifungal antibiotic (–)-(1R,2S)-2-aminocyclopentane-1-carboxylic acid (cispentacin)8 and its cyclohexane homologue 14 have been prepared utilizing the highly stereoselective conjugate addition of homochiral lithium N-benzyl-N-α-methylbenzylamide 5. The corresponding trans-β-amino acids 10 and 16 were also prepared via the selective epimerization of the cis-β-amino ester conjugate addition products.

1,2,3-trisubstituted cyclopropanes as conformationally restricted peptide isosteres: application to the design and synthesis of novel renin inhibitors.

The 1,2,3-trisubstituted cyclopropanes 6 and 7 are the first members of a novel class of isosteric replacements for peptide linkages that are more generally represented by the dipeptide mimics 2 and 3. These unique peptide surrogates are specifically designed to lock a section of a peptide backbone in an extended beta-strand conformation (phi-angle restriction) while simultaneously enforcing one of two specifically defined orientations for the amino acid side chain (chi 1-angle restriction). Methods were first developed for the stereoselective, asymmetric synthesis of the trisubstituted cyclopropanes 15a-d, 18a-d, 22a-d, and 23a-d (Scheme II), by an efficient approach featuring the Rh2(S-MEPY)4 (11) and Rh2(R-MEPY)4 (20) catalyzed cyclization of the allylic diazoacetates 10a-d to give the optically active lactones 12a-d and 21a-d, respectively, in up to greater than or equal to 94% enantiomeric excess. Nucleophilic opening of the lactone ring of 12a-d gave the corresponding morpholine amides 14a-d. By exploiting tactics that allowed for selective epimerization of one of the two functionalized side chains on the cyclopropane nucleus, 14a-d were transformed into the two series of diastereoisomeric morpholine amide carboxylic acids 15a-d and 18a-d. Epimerization of the morpholine amide group on 14a-d followed by Jones oxidation of the intermediate alcohols gave 15a-d. Alternatively, initial oxidation of the primary alcohol groups in 14a-d followed by selective, base-catalyzed inversion alpha to the aldehyde function and then Jones oxidation gave the diastereomeric dicarboxylic acid derivatives 18a-d. In a similar fashion, the enantiomeric lactones 21a-d were converted into the two corresponding enantiomeric series of dicarboxylic acid derivatives 22a-d and 23a-d. Inhibitors of aspartic proteinases, of which renin is a typical example, are known to bind to the enzyme active site cleft in an extended conformation. Thus, in order to evaluate the efficacy of 1,2,3-trisubstituted cyclopropanes as rigid replacements of beta-strand secondary structure in pseudopeptidic ligands, 15a-d, 18a-d, 22a-d, and 23a-d were incorporated at the P3 subsite of the potential renin inhibitors 24a-h and 25a-h by coupling with the tripeptide replacement 8. A significant number of substances inhibited renin at nanomolar concentrations. On the basis of this preliminary test, 1,2,3-trisubstituted cyclopropanes do appear to constitute a viable new class of peptide mimics. Since the stereochemistry at each carbon on the cyclopropane ring may be altered, these novel replacements may also function as stereochemical probes to establish the conformation of pseudopeptide ligands bound to their macromolecular targets.

ChemInform Abstract: A Convenient Reduction‐Oxidation Procedure of the Selective Epimerization at Sulfur of Highly Functionalized, Optically Active Sulfoxides.

AbstractThe chiral β‐hydroxymethyl sulfoxides (Ib) and (Id) are O‐protected to form the corresponding tetrahydropyranyl ethers (Ic) and (Ie).

Synthetic approaches to phorbols via the intramolecular Diels–Alder reaction of furans: influence of the dienophile upon the stereochemical control

A carbotricycle (13) having the same relative stereochemistry as the phorbols at 6 centres has been constructed via stereoselective Intramolecular Diels–Alder reaction of furans (IMDAF) of a precursor (7) possessing a Z-vinylogous ketoester followed by selective epimerisation at C-10 of the initial cycloadduct (11); whereas the corresponding E-isomer (8) or alkyne (3) show no stereoselection in the IMDAF.

A Convenient Reduction-Oxidation Procedure for the Selective Epimerization at Sulfur of Highly Functionalized, Optically Active Sulfoxides

Abstract A convenient method is described for the selective epimerizatin at sulfur of highly functionalized, optically active sulfoxides. The approach followed involves a sulfoxide reduction (with 2-phenylene phosphochloridite) - oxidation (with m-chloroperoxybenzoic acid) - separation of diastereomers sequence of steps. It was applied for the conversion of 3a, 3b and 3c into 2a, 2b and 2C, respectively, key intermediates in the total synthesis of the antitumor antibiotic sparsomycin and derivatives. Overall yields range from 26% to 37%.

Stereoselective reactions. XII. Synthesis of antitumor-active steganacin analogs, picrosteganol and epipicrosteganol, by selective isomerization.

New steganacin analogs with definite absolute configurations, (-)-picro- and (-)-epipicrosteganol, were synthesized by isomerization of (-)-steganol and (-)-episteganol, respectively, at the α-position to the lactone carbonyl. The structure of (-)-epipicrosteganol was confirmed by X-ray crystallographic analysis. Selective epimerization at the C-4 benzylic position was observed upon acidic treatment of (-)-steganacin, giving (-)-episteganacin.

Asymmetric synthesis of [C‐1‐3H]‐labelled (+)‐trans [1R,3R]‐chrysanthemic acid

AbstractA facile asymmetric synthesis of [C‐1‐3H]‐labelled (+)‐trans[1R,3R]‐chrysanthemic acid, required for biosynthetic studies is described. The tritium labelled acid is prepared from the corresponding (−)‐cis[1S,3R]‐ester by selective epimerisation of the C‐1 centre in the latter, in the presence of tritiated water.