Jadwiga Frelek

[Rh2(OCOCF3)4] as an auxiliary chromophore in chiroptical studies on steroidal alcohols

Abstract The circular dichroism (CD) of in situ formed complexes of steroidal substituted secondary and tertiary alcohols with [Rh2(OCOCF3)4] have been investigated. The applicability of the bulkiness rule, developed for unsubstituted secondary alcohols and connecting the sign of the E band at ca. 350 nm with the absolute stereochemistry of an alcohol, is extended to substituted secondary and tertiary alcohols. The rule works well for secondary and tertiary alcohols containing a double bond, alkoxy, ester or amide groups, halogen substituents as well as additional primary hydroxy groups in a molecule. The influence of other substituents present at the stereogenic center, e.g. a keto-, amino-, azido- or additional hydroxy groups, on CD is also described. It is demonstrated that alcohol molecules bind to the Rh-core at axial positions to form 1:2 adducts of the general formula [Rh2(OCOCF3)4(alcohol)2].

Spontaneous chiral resolution of a coordination polymer with distorted helical structure consisting of achiral building blocksDedicated to Professor Peter Jutzi on the occasion of his 65th birthday.

Reaction of achiral 2,5-diphenyl-3,4-di(3-pyridyl)cyclopenta-2,4-dien-1-one (2) with ZnCl2 and HgBr2, respectively, afforded the helically chiral coordination polymers [(2)ZnCl2]infinity and [(2)HgBr2]infinity, which show spontaneous chiral resolution, forming colonies of homochiral crystals.

Distinguishing between polymorphic forms of linezolid by solid-phase electronic and vibrational circular dichroism

For the first time two crystalline forms of the same compound (linezolid polymorphs) were investigated by means of the solid-phase ECD and VCD spectra. The ECD spectra show distinct differences and the band at 221 nm serves as a diagnostic one because it is present in form II but absent in form III. The VCD spectra strongly differ in the diagnostic carbonyl absorption range exhibiting two relatively strong bands of opposite signs.

1,3-Dipolar cycloaddition of a nitrone derived from (S)-malic acid to α,β-unsaturated δ-lactones

Abstract 1,3-Dipolar cycloaddition of nitrone 7 to α,β-unsaturated δ-lactones: non-chiral 2, racemic mixture 3/3ent, d -glycero 3 and d -threo 15 proceeds with high stereoselectivity in the case of 2 and 15, and with a significant kinetic resolution in the case of the racemate 3/3ent. The endo approach of reactants was not observed. CD-spectroscopy proved an attractive tool for determination of the absolute configuration of cycloadducts.

APPLICATION OF MO2(OAC)4 FOR DETERMINATION OF ABSOLUTE CONFIGURATION OF BRASSINOSTEROID VIC-DIOLS BY CIRCULAR DICHROISM

The in situ complexes of dimolybdenum tetraacetate [Mo2(OAc)4] with vicinal diols give CD spectra suitable for determination of their absolute configuration. Positive (negative) torsional angle in the O-C-C-O moiety leads to a positive (negative) Cotton effect at around 300 nm. The extension of this rule to compounds containing a second vic-diol moiety in the same molecule is studied on brassinosteroid vic-diols 1–14. It is demonstrated that the in situ method allows fast and easy configurational assignment of both glycol moieties present in brassinosteroids on the basis of the sum and difference CDs of respective pairs of (22S,23S)- and (22R,23R)-isomers. Chirality 9:578–582, 1997.

Double Asymmetric Induction in 1,3‐Dipolar Cycloaddition of Nitrones to 2,3‐Unsaturated Sugar 1,5‐Lactones

1,3‐Dipolar cycloaddition of nitrones 1–3 to the α,β‐unsaturated δ‐lactones, non‐chiral 4, d‐glycero 5, dl‐glycero 5/5ent, d‐erythro 6, and d‐threo 7, provides an interesting example of a double asymmetric induction. In all cases, only the exo approach of reactants was observed. The high preference of anti addition of the nitrones to the terminal acetoxymethyl group in the lactones 5–7 is consistent with previous observations, and can be explained in terms of the axial approach of the nitrone oxygen atom. The 3‐t‐butoxy group of the nitrone plays a similar role. In the case of mismatched pairs, the location of the 4‐acetoxy substituent in the lactone and that of the 4‐t‐butoxy one in the nitrone become decisive for the outcome of the addition. CD‐spectroscopy proved to be an attractive tool to determine the absolute configuration of the cycloadducts. †This paper is dedicated to Professor Gérard Descotes on the occasion of his 70th birthday.

Glucosylceramide Mimics: Highly Potent GCase Inhibitors and Selective Pharmacological Chaperones for Mutations Associated with Types 1 and 2 Gaucher Disease

A series of iminoxylitol derivatives carrying a C‐linked di‐O‐acyl or di‐O‐alkyl glyceryl substituent were prepared and characterized. All of these compounds, which were designed as glucosylceramide (GlcCer) mimics, were nanomolar inhibitors of lysosomal β‐glucosidase (glucocerebrosidase, GCase). Two of these pseudoglycolipids were further evaluated for their ability to enhance the activity of mutant GCase in human Gaucher cells. Although the di‐O‐hexyl ether was surprisingly devoid of chaperoning activity on both N370S and L444P GCases, the di‐O‐decanoyl ester was a potent chaperone of the L444P hydrolase, capable of increasing the residual activity of the enzyme by a factor of two at a very low concentration (50 nM); such a significant effect on the L444P mutation in human fibroblasts has not yet been observed. In heat‐stress studies, the diether was found to be much more effective in stabilizing the wild‐type enzyme than the diester. Four representative pseudoglycolipids were also assayed as inhibitors of GlcCer synthase, because such compounds could find use in the substrate reduction therapy approach to treat lysosomal storage diseases, but these compounds revealed only moderate activity. As efficient pharmacological chaperones, new structures such as the di‐C10‐ester constitute leads for the development of therapeutic agents for types 2 and 3 Gaucher disease, the most severe neuronopathic forms of this lysosomal disease.

Rearrangement of 23-oxospirostanes to the 22-oxo-23-spiroketal isomers promoted by Lewis acids—X-ray crystal structure of (23R,25S)-3β-acetoxy-16β,23:23,26-diepoxy-5β-cholestan-22-one

Both 25R and 25S 23-oxospirostanes undergo rearrangement to the 22-oxo-23-spiroketal isomers promoted by Lewis acids. An X-ray crystal structure analysis of the rearranged product of 23-oxosarsasapogenin acetate confirmed the R configuration at the new spiro carbon atom.

Configurational assignment of vic-amino alcohols from their circular dichroism spectra with dirhodium tetraacetate as an auxiliary chromophore

Abstract The in situ formed complexes of dirhodium(II) tetraacetate with optically active derivatives of the 1,2-amino alcohols ephedrine and adrenaline show circular dichroism spectra suitable for determination of their absolute configuration. According to the M- or P-helicity of the N–C–C–O moiety the investigated compounds generate negative or positive Cotton effects at around 300 and 440 nm, respectively. The third prominent CE of an opposite sign to the first two occurs at ca. 380 nm. It is demonstrated that the in situ method allows fast and easy configurational assignment based on the helicity rule that connects the signs of the Cotton effects at around 300 and 440 nm with the sign of the N–C–C–O torsional angle.

Chiroptical properties of steroid 1,3-diaxial diols in the presence of [Mo2(OAc)4]

SummaryBidentate complexes of dimolybdenum tetraacetate with 1,3-diaxial diols show Cotton effects around 490–540 nm (CD band I), 400–440 nm (II), 350–380 nm (III), 320 nm (IV) and 280 nm (V). The sign of the Cotton effect II can be predicted by a proposed sector rule. It seems that from the Cotton effects for cyclic 1,3-diols the absolute configurations or conformations can be obtained.