THE CONFORMATIONAL ANALYSIS AND PHOTOISOMERIZATION OF RETINOCHROME ANALOGS WITH POLYENALS

Abstract— 3, 7-Dimethyl-2, 4, 6, 8, 10-dodecapentaenal was synthesized for reconstitution of the retinochrome analog. Its opsin shift was 1000 cm ¹ smaller than that of native retinochrome, whose chromophore contains the same number of double bonds. The conformational change from 6-s-trans to 6-s-cis , as figured in a retinal molecule, plays an important role in the formation of the retinochrome analog, based on the estimation of opsin shifts for retinal analogs locked in the 6-s conformation. Thus the conformation of the 6–7 single bond in the native retinochrome was suggested to be 6 -cis . Analysis of the circular dichroic spectra of retinochrome analogs revealed that the 6-s conformation is independent of the appearance of the β-band. The stereoselectivity in the photoisomerization of the retinal analogs by a retinochrome template depends on the hydrophobic binding in the region of the β-ionone ring.     

Synthesis of 7-alkyl-2,4-dimethoxy-5-oxo-5H-pyrano[4,3-d]pyrimidines

A convenient synthesis of 7-alkyl-2,4-dimethoxy-5-oxo-5H-pyrano[4,3-d]pyrimidines from methyl 2,4-dimethoxy-6-phenylselenylmethyl (or 6-phenylthiomethyl)-5-pyrimidinecarboxylate with alkylaldehydes is described.     

Iodocyclization of hydroxylamine derivatives based on the control of oxidative aromatization leading to 2,5-dihydroisoxazoles and isoxazoles

An efficient method for the synthesis of 2,5-dihydroisoxazoles and isoxazoles using iodocyclization of N-alkoxycarbonyl O-propargylic hydroxylamines has been developed. 2,5-Dihydro-4-iodoisoxazole underwent the cross-coupling reactions without aromatization to afford polyfunctionalized 2,5-dihydroisoxazoles. This process was applied to the preparation of valdecoxib and its 2,5-dihydro-derivative.     

Total synthesis of myxol and deoxymyxol stereoisomers and their application to determining the absolute configurations of the natural products

The total synthesis of myxol stereoisomers 1a,b and deoxymyxol (plectaniaxanthin) stereoisomers 2a,b was accomplished by Wittig reaction of (S)- and (R)-C₁₀-phosphonium salts 8a,b bearing a silyl-protected 1,2-dihydroxy-ψ end group with C₃₀-apocarotenals 6 and 7. The phosphonium salts 8a,b were derived from aldehydes 11a,b possessing a cyclopentylidene ketal moiety, prepared via Sharpless asymmetric epoxidation of allylic alcohol 12 followed by regioselective cleavage of the oxirane ring. We established an analytical HPLC method using a chiral column to separate stereoisomers 1a,b and 2a,b and thus determined the absolute configurations of the natural products. The HPLC analyses established that both myxol and deoxymyxol isolated from bacteria have the 2′S-configuration.     

A convenient and stereoselective synthesis of 11Z-3,4-didehydroretinal by Horner-Emmons reaction using diphenyl phosphonate

A convenient synthesis of 3,4-didehydroretinal was developed. The Horner-Emmons reaction between 3,4-didehydro-beta-ionone and diphenyl phosphonate in the presence of crown ether gave the retinonitrile as an isomeric mixture, in which the newly produced double bond was predominantly 11Z-form. After separation of the 11Z-form retinonitrile, it was converted into the corresponding retinal in good yield without isomerization of the double bonds.     

Carotenoids and related polyenes, part 12. First total synthesis and absolute configuration of 3'-deoxycapsanthin and 3,4-didehydroxy-3'-deoxycapsanthin

The synthesis of 3'-deoxycapsanthin (1) and 3,4-didehydroxy-3'-deoxycapsanthin (2), carotenoids of paprika, has been achieved by employing Lewis acid-promoted regio- and stereoselective rearrangement of the C(15)-epoxy dienal 5a. The absolute stereochemistry of the newly formed C-5 chiral center of rearrangement product 6a was determined to be (R) from its alternative synthesis derived from (+)-(R)-camphonanic acid (11).     

Synthesis of 11Z‐9‐demethyl‐9‐((3‐indolyl)methyl)retinal

A convenient synthesis of 11Z‐9‐demethyl‐9‐((3‐indolyl)methyl)retinal, which has an amino acid residue of tryptophan at the 9 position in retinal, is described using a tricarbonyliron complex.     

Iodocyclization of ethoxyethyl ethers to alkynes: a broadly applicable synthesis of 3-iodobenzo[b]furans

A wide variety of 3-iodobenzo[b]furans were readily prepared by iodocyclization of 2-alkynyl-1-(1-ethoxyethoxy)benzenes with the I(coll)2PF6-BF3 x OEt2 combination. Aryl-, vinylic-, and alkyl-substituted alkynes undergo iodocyclization in good to excellent yields. The mechanism of the reaction is also discussed.     

Synthesis of gamma-hydroxybutenolides applying crossed aldol condensation in the presence of a bulky lewis acid and their anti-tumor activity

An improved synthesis of gamma-hydroxybutenolides 1a-d was achieved via crossed aldol condensation between aldehydes 2a-d and the protected gamma-hydroxy-beta-methylbutenolides 3 or 4 using the bulky Lewis acid, aluminum tris(2,6-diphenylphenoxide) (ATPH). Using this same methodology, the gamma-hydroxybutenolides 17a-d having various heteroaromatic rings were synthesized and their anti-tumor activities were evaluated.     

An improved synthesis of benzocycloalkanone derivatives

A convenient and improved annulation method for the synthesis of bicyclic ketones was developed. A 2,2-dimethyl-6-(2-phenylsulfonyl)ethylcyclohexanone was converted into a sulfonylester by the addition of ethyl acetate and subsequent dehydration. A Dieckmann type condensation of the sulfonylester followed by desulfonylation afforded the 8,8-dimethyl-1,2,3,4,5,6,7,8-octahydronaphthalene-2-one in good yield. This annulation method was also applicable for the synthesis of the benzocyclooctanone derivative.