Diastereomeric Adducts Research Articles

Diels-Alder reactions of 1,2-(1,1'-binaphthalene-2,2'-diyldisulfonyl)ethylene with symmetrical and unsymmetrical dienes

The C 2 -symmetrical chiral reagent 1,2-(1,1'-binaphthalene-2,2'-diyldisulfonyl) ethylene (1) is a reactive dienophile and forms Diels-Alder adducts with symmetrical and unsymmetrical dienes. In the case of unsymmetrical dienes the reaction affords, in most cases, a single diastereomeric adduct whose stereochemistry has been determined by NMR spectroscopy and confirmed by X-ray structure determination of selected adducts. The arylsulfonyl groups can be removed with formation of a double bond, making 1 a chiral synthetic equivalent of acetylene in [4+2]-cycloaddition reactions. The binaphthyl auxiliary can be recovered and recycled

Active site interactions in hydrated trypsin-organophosphate adducts: a yeti molecular mechanics study

Two diastereomers (P R, P S) of 2-propyl methylphosphonate covalently bonded to Ser-195 of bovine trypsin have been generated from appropriate X-ray crystallographic coordinates. The corresponding enzymic dealkylation product, the methylphosphonate anion, has also been modeled for each diastereomer. In addition to 168 experimentally determined water molecules, 101 water molecules were generated with the program SOLVGEN and the structure was refined with the molecular mechanics program YETI. The partial atomic charges for the seryl-phosphonate moiety were generated with the MNDO method AMPAC. Zone refinements around the active sites Hip-57, Asp-102, Ser-214 and the Ser-195-bound inhibitor fragment were performed for 62 residues on each of the diastereomeric adducts and their reaction products. The diastereomer adduct P S gives the more stable conformation, which suggests that the other diastereomer P r will undergo preferential dealkylation. This more labile conformation corresponds to the “up” position in diisopropyl phosphate, from which dealkylation is known to occur in favor of the “down” position. The dealkylation product from the P R diastereomer is 3.7 kcal mol − more stable than that from the P S diastereomer.

ChemInform Abstract: Synthesis of (S)‐β,β,β‐Trifluorolactic Acid and (S)‐α‐Methoxy‐α‐(trifluoromethyl)phenylacetic Acid from (R)‐Methyl p‐Tolyl Sulfoxide.

AbstractThe optically active sulfoxide (R)‐(I) is coupled with the trifluorocarbonyl compounds (II) to give the diastereomeric adducts (III) as the main products.

Influence of polypeptides on the reactivity of thiols toward iron(III) complex ions

Oxidation of L-cysteine by quaterpyridineiron( III) complex ions (FeT) anchored to ordered poly(L-glutamate) or poly(D-glutamate) was studied in the pH range 7–8. Surprisingly, electron transfer from substrate to the central metal ion does not take place, despite the favorable thermodynamic driving force. Instead, a stable, polymer-supported Fe IIIT-cysteinate complex forms, to which no stereoselectivity is associated. This finding contrasts the known lability of Fe III-thiolate complexes, ultimately yielding disulfides and iron( II) species, and is relevant in view of the current interest in model compounds of cytochrome P-450, where cysteine is axially bound to ferric porphyrin. The formation of this complex was studied by kinetics and low-temperature electron paramagnetic resonance spectroscopy. The stereochemical features of the diastereomeric adducts were investigated by theoretical conformational analysis and compared with those already computed for the encounter complexes with some L-dihydroxy substrates. The results collectively emphasize the environmental control of the polypeptide matrix on the stability of cysteinate sulfur axial ligation.

Radical identification by liquid chromatography/thermospray mass spectrometry

Radical adducts of 5,5-dimethyl-1-pyrroline N-oxide (DMPO) with hydroxyl, methanol-derived, and ethanol-derived radicals were detected by a combination of liquid chromatography with either electron paramagnetic resonance or thermospray mass spectrometry (LC/EPR or LC/TSP-MS) in the Fenton system (with methanol or ethanol). One radical adduct was observed in the reaction of DMPO with the hydroxyl radical or the methanol-derived radical, while two adducts were detected in the reaction of DMPO with ethanol-derived radicals. The LC/TSP-MS spectra showed quasi-molecular ions [M + H]+ at m/z 146 and m/z 160 for the methanol-derived and ethanol-derived radical adducts, respectively, and an apparent molecular ion M+ at m/z 130 for the hydroxyl radical adduct. Use of methyl-D3 alcohol (CD3OH) and ethyl-D5 alcohol (CD3CD2OH) indicated that carbon-centered radicals are formed. Experiments with partially deuterated ethanol (CD3CH2OH and CH3CD2OH) indicated that the two adducts observed in the reaction of DMPO with ethanol-derived radicals correspond to the two diastereomeric adducts of DMPO with the alpha-hydroxyethyl free radical.

ChemInform Abstract: Diels‐Alder Reactions of Acyclic Chiral Alkoxy Dienes: Oxygen versus Sulfur as an Allylic Directing Group.

AbstractThe optically active aldehydes (I) are converted to the protected dienols (IV) which undergo (4 + 2)cycloaddition reaction with the dienophiles (V), yielding the diastereomeric adducts (VI) and (VII).

Diastereoselective additions of lithiated N- tertbutyldiphenylsilyl- S-methyl-S-phenylsulfoximine to imines and aldehydes

Lithiated N-tert-butyldiphenylsilyl-S-methyl-S-phenylsulfoximine undergoes 1,2 addition to imines (R 1CHNPh) and aldehydes (RCHO) to give diastereomeric adducts. The diastereoselection of the former reactions is dependent on the steric demand of the imine substituent R 1, while that of the latter is independent of the steric demand of the aldehyde substituent R.

ChemInform Abstract: Functionalized 2‐Azabicyclo(3.3.1)nonanes. Part 10. α,α′‐Anellation of 1‐Benzyl‐2,5‐piperidinedione and Isolation of an Azabicyclic Adduct as Stable Hydrate.

AbstractThe piperidinedione (I) is converted to the enamine (III) and then treated with acrolein (IV), yielding the diastereomeric adducts (V).

ChemInform Abstract: Effective Synthesis of Optically Active 2‐Methyl‐1,2‐hexanediols.

AbstractThe chiral oxathiane (I) reacts with butyllithium and 2‐hexanone (II) to yield the diastereomeric adducts (III) which are oxidatively cleaved after chromatographic separation, forming the optically active aldehydes (IV).

ChemInform Abstract: Cycloaddition Reactions of 3,4‐Dihydro‐2H‐pyran with Benzylideneanilines.

AbstractBenzylideneaniline (I) and dihydropyran (II) undergo cycloaddition reaction in the presence of iron(III) chloride, forming the diastereomeric (4 + 2)adducts (III) and (IV).

ChemInform Abstract: Titanium as a Regio‐ and Stereoselective Control Element in the Reaction of α‐Alkoxyallylic Phosphine Oxide Anions with Carbonyl Compounds.

AbstractCondensation of the methoxyallylphosphine oxides (I) with the aldehydes (III) proceeds at the α‐position of the allyl system to give the diastereomeric adducts (IV) and (V).

Depurination and imidazole ring-opening in nucleosides and DNA alkylated by styrene oxide

Styrene-7,8-oxide was reacted with guanosine and deoxyguanosine and four isomeric 7-alkylguanosines were isolated, two of each being substitutions through the α and β carbon of styrene oxide. The diastereomeric adducts imidazole ring-opened at an identical rate but the α- and β-adducts differed (half-lives 90 and 56 min, respectively, pH 10, 24°C). The 7-β alkyldeoxyguanosine derivatives ring-opened at a six times slower rate, which was similar to 7-methyldeoxyguanosine. The diastereomeric guanosine products also depurinated at the same rate but the β-derivatives depurinated faster than the α-derivatives ( t 1 2 35 vs. 79 min, respectively, pH 1, 70°C). The differences in the ring-opening and depurination of the α- and β-isomers corresponded to their respective p K a values (7.31–7.32 vs. 7.16–7.19). The 7-alkyldeoxyguanosine derivatives of styrene oxide depurinated equally fast as 7-methyldeoxyguanosine. By contrast, the depurination of 7-alkylguanine was 15 times slower in the single-stranded DNA and 55 times slower in the double-stranded DNA.

Conjugate addition of amines to chiral (E) and (Z) vinyl sulfoxides, an enantioconvergent and kinetic process

The kinetically controlled conjugate addition of benzylamine to isomeric ( E) or ( Z) chiral vinyl sulfoxides affords the same major diastereomeric adduct

Intramolecular diels-alder reaction with furan-diene. Comparison of reactivity and stereoselectivity within a set of structurally related substrates of

The reactivity and stereoselectivity of the intramolecular cycloaddition of a set of structurally related Diels-Alder precursors 2–6 is studied. The kinetically controlled cycloaddition of acetylene 2 yields in refluxing benzene a mixture of 7 and 8 in which the latter predominates. The allene-derivative 3b was found to cycloadd at room temperature at the unactivated π-bond to yield a single adduct 9b . The structural elucidation of adducts 7b , 8a and 9b was solved by X-ray diffraction. Olefin 4 gives the adduct 12 as sole diastereomeric adduct. A model is proposed for rationalizing the observed stereochemical outcome.

ChemInform Abstract: Synthesis of Optically Active Litsenolide C.

AbstractCoupling of the lithium enolate (II), derived from an α‐phenyl thioester, with the optically active aldehyde (R)‐(I) gives the diastereomeric adducts (III) which are cyclized to form the γ‐lactones (IV).

ChemInform Abstract: Unusual Applications of Oxygen Heterocycles in Synthesis

A program underway in the author's lab to examine the production and synthetic utility of 1 ,2-hydroxycycloalkanones and derivatives is described. Emphasis is placed on the synthesis of optically pure, biologically active, natural products. THE SULFOXIMINE ROUTE Compound 1 is rapidly deprotonated with butyllithium in tetrahydrofuran to provide methylphenylsulfonimidoylmethyllithium (2). Additions of optically pure 1 (as the lithio reagent 2) to a simple acydic prochiral ketone or aldehyde results in the production of two optically active diastereomeric adducts 31 We have found these 3-hydroxysulfoximines (3) are thermally unstable and revert to the starting carbonyl compound and sulfoximine in the temperature range of 80 to 1200 C. lb The reversion is probably facilitated by the transfer of the OH proton to the sulfoximine nitrogen such that carboncarbon bond cleavage occurs with the ylide 4 as the leaving group. The ylide selfquenches by tautomerization to the starting sulfoximine (Scheme 1). One might envision the overall procedure of adduct formation and thermal release of the starting materials as a carbonyiprotection/deprotection procedure. The deprotection step is especially intriguing in that it occurs without the intervention of acid or base. Scheme 0 0 0 II n-Bull II K Ph S Me Ph S CH2 Li ____________ Ph II THFOC II ThF,-78C MeN 0 80120'C MeN MeN thenH H

ChemInform Abstract: Asymmetric Hydrogenation of Methyl‐(Z)‐α‐acetamidocinnamate Catalyzed by (1,2‐Bis((phenyl‐o‐anisoyl)phosphino)ethane)rhodium(I): Kinetics, Mechanism, and Origin of Enantioselection.

AbstractThe less stable of the two diastereomeric adducts (III) leads to the predominant product enantiomer (IV) by virtue of its much higher reactivity toward H2.

Unusual applications of oxygen heterocycles in synthesis

Abstract

Aminoglycoside Antibiotics – Fortamine Aglyca Total Synthesis, Optical Resolution, Chemical Modifications

AbstractStarting from the dianhydro‐epi‐inositol 10 (available ultimately from benzene) an expedient total synthesis of enantiomerically pure (+)/(−)‐de‐O‐methylfortamines (derivatives) has been developed. Key steps are the regiospecific epoxide openings which occur intramolecularly in the diepoxybis(urethane) 11 and intermolecularly by (+)‐1‐phenylthylamine in the epoxyurethanes rac‐13. The diastereomeric adducts (30, 32) are quantitatively separated by crystallization/chromatogrphy. Following hydrogenation, natural and nonnatural cis‐1,4‐inosadiamines are obtained optically pure [e.g. fortamine (−)‐1, ent‐fortamine (+)‐1, 3‐O‐demethylfortamine (−)‐38, ent‐3‐O‐demethylfortamine (+)‐38]. This approach, which was optimized by numerous model reactions, allows wide chemical modifications and leads among others to 3‐O‐demethylfortamine and ent‐fortamine derivatives in which only the (6)4‐OH‐group, the one to be glycosidated, remains unprotected.

ChemInform Abstract: Stereoselective Addition of Lithioethyl Acetate to Boc‐L‐prolinal. A Convenient Chiral Synthetic Building Block for the Pyrrolizidine Alkaloid Ring System.

AbstractThe prolinal (II), obtained by reduction of the ester (I), reacts with lithioethyl acetate (III)to give the diastereomeric adducts (IV).