Alfred E. Asato

Fluorinated Retinoids via Crossed Aldol Condensation of 1,1,1-Trifluoroacetone☆

Abstract Piperidine-acetic acid catalysed crossed aldol condensation of 1,1,1-trifluoroacetone with aryl or α,β-unsaturated aldehydes was found to be a useful method for the preparation of unsaturated trifluoromethyl ketones. Chain extension of these ketones led to several new fluorinated retinoids including the hitherto elusive all-trans isomers of 19,19,19- and 20,20,20-trifluororetinal.

[65] Synthesis and photochemistry of stereoisomers of retinal

Publisher Summary This chapter discusses the synthesis and photochemistry of stereoisomers of retinal. Recently, Because of the availability of better separation methods such as high-pressure liquid chromatography new geometric isomers are now known. Among those containing the 7- cis geometry, five ( 7- cis, 7,9-di cis , 7,9,13-tr icis , 7,13-di cis , and 7,11-di cis) have been isolated and their geometry unambiguously characterized. The two remaining 7- trans isomers (9,11-di cis and 9,11,13-tri cis) have also been prepared. Additionally, the 7,11,13-tri cis , 8 7,9,11- tri cis, and the all-cis isomers 7 of retinonitrile have been synthesized. In 7- cis- retinal preparation from direct irradiation of the all-trans isomer, ethanol is used as a solvent. In synthesis, all-trans-retinal is dissolved in acetonitrile and placed behind filter plate, the solution is irradiated externally with medium-pressure mercury lamp. The irradiated mixture is concentrated by evaporation on a rotary evaporator. The isomers are separated by preparative high-performance liquid chromatography (HPLC) using conditions identical to those for analysis. It is reported that in any organic structure determination, nuclear magnetic resonance spectroscopy is the reliable method for characterizing the stereochemistry of the polyene chain of the retinal isomers because of the nondestructive nature of the method and the increased sensitivity of the newer spectrometers.

9-Cis 11-cis isomers of 18,18,18-, 19,19,19- and 20,20,20-trifluororetinal

Abstract The preparation and properties of the 9-cis and 11-cis isomers of three trifluoromethylated retinals are described.

Azulene-containing donor-acceptor compounds as second-order nonlinear chromophores

Abstract Several novel, thermally stable azulene-containing donor-acceptor molecules were synthesized and their second-order nonlinear optical properties determined by the EFISH method. The βμ-values for these new compounds featuring azulene as the pi-electron donor were comparable with NLO compounds containing para-N,N-diethylaniline as the electron-donor.

The preparation of vicinal difluoroolefinic carbonyl compounds and their application to the synthesis of difluororetinal analogs

Abstract The preparation of a novel vicinal difluorinated retinal analog is described. The key difluoroolefinic intermediate in the synthesis was prepared by the reaction of DAST with ethyl acetoacetate.

ANALYZING THE RED‐SHIFT CHARACTERISTICS OF AZULENIC, NAPHTHYL, OTHER RING‐FUSED AND RETINYL PIGMENT ANALOGS OF BACTERIORHODOPSIN*

Prompted by the near infrared‐absorbing properties of some of the azulenic bacteriorhodopsin (bR) analogs, we have analyzed their absorption characteristics along with 11 new related ring‐fused analogs and the corresponding Schiff bases (SB) and protonated Schiff bases (PSB). The following three factors are believed to contribute to the total red shift of each of the pigment analogs (αRS): perturbation of the basic chromophore (SB shift, ΔSB), protonation of the SB (PSB shift, PSBS) and protein perturbation (the opsin shift, OS). For each factor, effects of structural modifications were examined. For the red‐shifted pigments, percent OS has been suggested as an alternate way of measuring protein perturbation. Computer‐simulated chromophores provided evidence against any explanation involving altered shapes of the binding pocket as a major cause for absorption differences. Implications of the current bR results on preparation of further red‐shifted bR and possible application to visual pigment analogs are discussed.

SHAPE OF THE CHROMOPHORE BINDING SITE IN PHARAONIS PHOBORHODOPSIN FROM A STUDY USING RETINAL ANALOGS

Abstract To investigate the shape of the chromophore binding site of pharaonis phoborhodopsin (ppR), ppR‐opsin was incubated with five ring‐modified retinal analogs: an acyclic retinal, phenylretinal, α‐retinal, cyclohexylretinal and 5‐isopropyl‐α‐retinal. The experimental results were compared with those obtained from bacteriorhodopsin‐opsin (bR‐opsin) and the same retinal analogs. It was suggested that ring chain conformation is important in affecting the spectral shoulder unique for the absorption spectrum of ppR. The rate of pigment formation depended greatly on the analogs used with the planar analogs showing rapid formation. Thus, we concluded that the space of the retinal binding site of ppR is restricted to the plane of the cyclohexenyl ring of the chromophore, whereas that of bR is less restricted.

The proline and β-lactoglobulin mediated asymmetric self-condensation of β-ionylideneacetaldehyde, retinal and related compounds.

Abstract Proline was found to effectively mediate the asymmetric reaction of β-ionylideneacetaldehyde 1A , retinal and related α,β-unsaturated aldehydes to form their corresponding self-condensation products in reasonable enantiomeric excess (up to 65% ee). This same interesting conversion was also observed when 1A was incubated in the presence of the milk whey protein β-lactoglobulin (BLG).

7‐cis‐PORPHYROPSIN FROM 7‐cis‐3‐DEHYDRORETINAL AND CATTLE OPSIN

Abstract 7‐cis‐3‐Dehydroretinol, prepared by photoisomerization of the all‐trans isomer in a polar solvent, was found to combine with cattle opsin to form a visual pigment analogue with an absorption maximum at 464 nm. The pigment is only moderately stable in hydroxylamine or in Ammonyx LO. and cannot be purified by column chromatography using Ammonyx LO. 9‐cis‐Porphyropsin, prepared in a manner similar to that reported by Azuma et al., is stable and has been purified by passing through a hydroxylapatite column. Three fractions were collected with eluant of increasing ionic strength. All fractions exhibit similar absorption properties with Λmax at 498 nm. These results further indicate that the binding of opsin is a flexible one.

The Nature of the Delocalized Cations in Azulenic Bacteriorhodopsin Analogs

Abstract Depending on the size and shape of their azulenic chromophores, azulenic bacteriorhodopsin (bR) pigment analogs can exist as either an initial pigment P1, a more red-shifted final pigment P2 or an equilibrium mixture of both. The absorption spectra of red-shifted bR analogs exhibit characteristic narrow-band shapes similar to charge fully delocalized cyanine-like dyes. Therefore, all such red-shifted pigments are believed to be highly delocalized, bond-equalized carbocations. We have determined structural requirements that facilitate their formation. To describe fully the red-shift potentials of these retinal analogs, we have introduced a new parameter—percent red-shift (PRS). A large PRS value not only reflects the extent of red-shift, but is also suggestive of extensive delocalization of the positive charge. Relevance of these findings in consideration of the possibility of forming stable O-intermediates is presented. The postulated resonance hybrid-like structures for different cations of the positively charged protonated Schiff base chromophores are in fact structurally distinct species, equilibrating in response to local perturbations within the supramolecular protein environment.