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Iron(III)Porphinate/H202-Mediated Conversion of All-(Zs)-Retinol

Doris Waldmann, Thorsten König, Peter Schreier*Lehrstuhl für Lebensmittelchemie, Universität Würzburg, Am Hubland,D-97074 Würzburg, GermanyZ. Naturforsch. 50b, 589-594 (1995); received October 13, 19945,6- and 5,8-Epoxyretinol, 4-Hydroxyretinol, 4-Oxoretinol, Retinol Conversion

The reaction of hydrogen peroxide with all-(£)-retinol (1) catalyzed by (meso-tetraphenyl- porphinato)iron(III) led to the formation of 4-hydroxyretinol (2), 4-oxoretinol (3), 5,8-epoxy- retinol (4), 5,6-epoxyretinol (5), 3-dehydroretinol (6), all-(£)- and 12-(Z)-retroretinol (7/7a) as well as all-(£')- and 12-(Z)-anhydroretinol (8/8 a) as major non-volatile products. The con­version products were characterized by comparison of their chromatographic (HPLC) and spectroscopic data (UV; MS; 'H and 13C NMR) with those of synthesized reference com­pounds. The observed product formation supports the hypothesis of a C4 centered radical as the key intermediate of all-(£')-retinol conversion.

Introduction

In the past, the stability of all-(£’)-retinol (vita­min A alcohol) (1) and its esters against acids [1], heat [2], transitient metals [3] and oxygen [4] has been studied extensively. As to oxidative reac­tions, however, only a few information about the products formed is available [5,6], In addition, the activity of 1 in cancer chemoprevention [7] has been related to its oxidative transformation, but only little is known about the metabolites formed in vivo [8].

It was the aim of our study to use (meso-tetra- phenylporphinato)-iron(III) (Fe3+-TPP)-H20 2 as a simple model system for the oxidative conver­sion of retinol (1). The importance of metallo- porphyrin catalyzed oxidations in biological sys­tems has brought considerable attention to metal complex mediated reactions [9].

Materials and MethodsAll commercial chemicals used were of analyti­

cal grade quality; solvents were of high purity at purchase and were redistilled before use. All-(£')- retinol (1), retinal and retinyl acetate were from Fluka, Neu-Ulm. N-bromosuccinimide, pyridinium dichromate, diisobutylaluminium hydride (1.5 M in toluene), lithium tris[(3-ethyl-3-pentyl)oxy]- aluminium hydride and (weso-tetraphenylporphi- nato)iron(III) (Fe3+-TPP) were purchased from

* Reprint requests to Prof. Dr. P. Schreier.

Aldrich, Neu-Ulm. Column chromatography was carried out with Merck silica gel 60.

Fe3+-TPP/H 2O2 catalyzed conversion o f retinol (1)

Fifty mg (35 mM) of retinol (1) and 3.5 mg (1 mM) of Fe3+-TPP were dissolved in 5 ml CH2C12/ CH3OH (1 :3). The reaction was initiated by addi­tion of 0.6 mg (1 mM) 30% hydrogen peroxide and allowed to continue under stirring at 30 °C until >95% of the retinol was decomposed (HPLC-UV control). The reaction was stopped by the addition of 0.9 mg (1 mM) BHA and immedi­ately analyzed by HPLC-UV.

High performance liquid chromatography (HPLC)

HPLC analyses were performed under (a) re­versed phase and (b) normal phase conditions using a Knauer HPLC pump 64 gradient system and a Hewlett Packard 1040A diode-array detec­tor interfaced with a HP 9153 C computer system,(a) Eurospher 100 C-18 columns (250 mm x 4.6 mm i.d.; 250 mm x 16 mm i.d.; 5 jum\ Knauer, Ber­lin) were employed at flow rates of 1.0 ml/min and 5.0 ml/min, respectively, using methanol-water- gradients, (i): 5 min 70% MeOH isocratic, then increased up to 100% M eOH in 15 min. (ii): 70% MeOH at t = 0 min and 100% M eOH at t = 25 min. (b) Lichrospher Si 100 columns (250 mm x4.6 mm i.d.; 250 mm x 16 mm i.d.; 5 /um Knauer, Berlin) were employed at flow rates of 0.9 ml/min and 4.5 ml/min, respectively, using (iii) methyl tert. butyl ether + pentane (4 + 6. v/v) as eluent. UV- VIS spectra in the range of 200-450 nm were recorded.

0932 - 0776/95/0400 - 0589 $06.00 © 1995 Verlag der Zeitschrift für N aturforschung. All rights reserved.

590 D. W aldm ann et al. ■ Iron (III)Porphinate/H 202-M ediated Conversion of A ll-(£')-Retinol

Capillary gas chromatography (HRGC)

(a) A Carlo Erba Mega 5160 gas chromatograph equipped with a J& W fused silica DB-Wax capil­lary column (30 m x 0.259 mm i.d.; film thickness 0.25 /zm) and FID was used. Split injection (1:20) was employed. The tem perature program was 3 min isothermal at 50 °C, then increased from 50 to 240 °C at 4 °C/min. The flow rate for the carrier gas was 2.0 ml/min He and for the makeup gas 30 ml/min N2; for the detector gases the flow rates were 30 ml/min H 2 and 300 ml/min air. Injector and detector temperatures were kept at 220 and 260 °C, respectively.

(b) A Hewlett-Packard 5890A gas chromato­graph equipped with a J& W fused silica DB-5 capillary column (30 m x 0.259 mm i.d.; film thick­ness 0.25 /um) and FID was used. Split-injection (1:20) was employed. The tem perature program was 60 °C to 300 °C at 5 °C/min. The flow rate of the carrier gas was 1.6 ml/min He and for the makeup gas 30 ml/min N2; for the detector gases the flow rates were 30 ml/min H 2 and 300 ml/min air. Injector and detector tem perature were kept at 250 °C.

Capillary gas chromatography-mass spectrometry (HRGC-M S)

A Varian 3400 gas chromatograph with split-in- jection (1:20) was combined by direct coupling to a Finnigan MAT 44 S mass spectrometer with PCDS data system. The same types of columns and the same temperature programs as mentioned above for HRGC were used. Temperature of ion source and all connection parts, 220 °C; electron energy, 70 eV; cathodic current, 0.7 mA; mass range 41-250.

Reference compounds

4-Hydroxy retinol (2): Treatment of 80 mg (0.56 mmol) retinal with 100 mg (0.56 mmol) N-bromo- succinimide in CH2C12 (7.5 min; 0 °C; Ar) pro­vided an unstable allylic bromide. After stirring (24 h; 20 °C; Ar) with AcOH and KOAc in ace­tone/water (9:1) a 4:1 mixture of 4-hydroxyretinal and 4-acetoxyretinal was obtained [10]. To a solu­tion of 50 mg (about 0.17 mmol) of this mixture in 10 ml of toluene ( -7 °C) 0.25 ml of 1.5 M diisobu- tylaluminium hydride solution in 12 ml toluene was dropwise added under stirring (20 min; - 7 °C; Ar). The reaction mixture was poured carefully to a mixture of ice and 250 ml methanol. The solution was concentrated under reduced pressure and the aqueous phase extracted twice with E t20 . The

combined organic layer was washed with saturated N aH C 0 3 solution, H20 , saturated NaCl solution and dried over Na2S 0 4. After filtration and solvent evaporation under reduced pressure an oily product was obtained. Column chromatogra­phy on S i0 2 (50% EtOAc/hexane) afforded 42.5 mg (85%) of 4-hydroxyretinol (2) (spectroscopic data, cf. Table I).

4-Oxoretinol (3): To a solution of 70 mg (0.24 mmol) of 4-hydroxyretinal (synthesized according to [10]) in 10 ml CH2C12 (0 °C; Ar) 1.7 g (4.6 mmol) pyridinium dichromate was added and the mixture was allowed to stirr at room temperature for 1.5 h. After adding of 200 ml of H 20 the sus­pension was extracted several times with E t20 . The combined organic layer was dried over

Table I. Spectroscopic data of 4-hydroxyretinol (2).

U V (M eO H ) [Amax] 326 nm (e 52000)EI-MSa [m/z(%)] M + 302 (13). 246 (9), 201 (12), 173 (13).

119 (18), 91 (22), 71 (35), 43 (100)'H N M R b [d] 1.015 (s, 6 H, H-16, H-17), 1.3 (m, 2H , H-

2), 1.7 (m, 2H . H-3), 1.82 (s, 6 H, H-18, H-19), 1.95 (s, 3H . H-20), 3.79 ( t , 1H. 7, = 4.8 Hz, J2 = 4.4 Hz, H-4), 4.30 (d. 2H , 7 = 6 .8 Hz. H-15), 5.68 (m. 1 H. H-14), 6.09 (1H. d, 7 = 14.3 Hz, H-8 ), 6.12 (d, 1 H, 7 = 11.4 Hz, H-10), 6.29 (d, 2H . 7 = 15.2 Hz, H-7, H-12), 6.60 (dd, 1H. 7, = 11.3 H z,72 = 14.8 Hz, H - ll)

,3C NM RC [d] 12.6 (C 19), 15.2 (C20), 20.3 (C18), 27.5(C 17), 28.4 (C3), 29.0 (C16), 34.5 (C2).34.7 (C l) , 59.3 (C15), 70.2 (C4), 124.7 (C 14), 125.6 (C7), 130.6 (C5), 131.0 (CIO, C l l ) , 135.5 (C 9), 136.5 (C13),136.9 (C12), 138.6 (C 8 ), 141.8 (C 6 )

a 70 eV; b 200 MHz, CDC13, ppm, <5 relative to Me4Si: c 50.3 MHz, CDC13, ppm, d relative to Me4Si.

Table II. Spectroscopic data of 4-oxoretinol (3).

UV (M eO H ) [/lmax] 336 nm (e 54000)EI-MSa [1m/z{%)] M+ 300 (2), 279 (4), 167 (24), 149 (73).

121 (5), 104 (9), 71 (43), 57 (85), 43 (100) 'H NM R b [d] 1.18 (s, 6 H. H-16, H-17), 1.40 (s, 3H , H-

18), 1.42 (s, 3H. H-19). 1.50 (s, 3H , H-20). 1.82 (m. 2H, H-2), 2.53 (m. 2H , H-3), 4.31 (d. 2H. 7 = 6.7 Hz. H-15), 5.73 (t.7 = 7.2 Hz. 1H. H-14), 6.15 (1H . d. 7 = 11.2 Hz. H-10). 6.28 (d. 2H . 7 = 15.2 Hz. H-7. H-8 ). 6.35 (d. 1 H, 7 = 15.2 Hz. H- 12), 6.61 (dd, 1H. 7, = 10.8 Hz, 7 , = Hz. H -ll)

13C NM RC [<3] 12.5 (C 19), 12.6 (C20), 13.7 (C18), 27.6(C 17), 27.6 (C 16). 34.3 (C3). 35.7 (C l) .37.4 (C 2), 59.5 (C15), 124.5 (C14). 125.8 (C 7), 130.5 (C5), 131.6 ( C l l ) , 133.7 (CIO), 134.8 (C9), 136.5 (C13), 138.5 (C 12), 141.1 (C 8 ), 161.5 (C 6 ), 199.3 (C4)

a 70 eV; b 200 MHz, CDC13, ppm. d relative to Me4Si: c 50.3 MHz, CDCI3 , ppm. d relative to Me4Si.

D. W aldm ann et al. • Iron(III)Porphinate/H 202-M ediated C onversion of A ll-(£ ')-R etinol 591

Table III. Spectroscopic data of all-E-(7)- and 12-Z- (7 a) retroretinol.

U V (M eOH) [Amax] 7 326, 346, 366 nm (e 54500)7a -270, 324, 344, 364 nm (e 54500)

EI-M Sa [m/z(%)] M+ 286 (38), 213 (2), 157 (22), 145 (22), 119 (35), 105 (53), 91 (52), 55 (67), 41 (100)

>H N M R h [Ö] 7 1.29 (s, 3H, H-16), 1.29 (s, 3H , H-17), -1 .5 (m, 2H, H-2), 1.84 (s, 3H , H-18),1.91 (s*, 3H, H-19), 2.09 (s*, 3H , H-20), -2 .32 (m, 2H. H-3), 2.36 (t, 2H , 7, = 6.1, J2 = 13.1, H-14), 3.72 (t, 2H , 7, = 6.5, J2 =11.7, H-15), 4.47 (d, 1 H, 7 = 15.4, H-10),5.76 (t, 1 H, 7, = 4.0, J2 = 8.4, H-4), 6.05 (d, 1 H, 7 = 10.2, H-12), 6.32 (d, 1H, 7 =10.3, H-7), 6.46 (d, 1 H, 7 = 10.5, H-8 ),6.79 (dd, 1H, 7, = 10.3, J2 = 15.7, H - ll )

7a 1.29 (s, 3H. H-16), 1.29 (s, 3H , H-17),-1 .5 (m, 2H , H-2), 1.84 (s, 3H , H-18),1.91 (s*, 3H, H-19), 2.09 (s*, 3H , H-20), -2 .32 (m, 2H , H-3), 2.50 (t, 2H , 7, = 6.1, J2 = 13.1, H-14). 3.72 (t, 2H , Jx = 6 .5 ,72 =11.7, H-15), 4.47 (d, 1 H, 7 = 15.4. H-10),5.76 (t, 1H, 7, = 4.0, 72 = 8.4, H-4), 6.05 (d, 1H, 7 = 10.2, H-12), 6.32 (d, 1 H, 7 =10.3, H-7), 6.46 (d, 1 H, 7 = 10.5, H-8 ),6.79 (dd, 1 H, 7, = 10.3, J2 = 15.7, H - ll )

13C NM RC [d] 7 12.0 (C19), 12.0 (C20), 21.6 (C18), 22.9(C3), 28.9 (C 16), 28.9 (C17), 35.8 (C l) ,40.7 (C2), 43.1 (C 14), 60.5 (C15), 120.0 (C7), 123.4 ( C l l ) , 127.8 (C 4), 128.3 (C12), 128.3 (C 8 ), 129.2 (C 5), 129.9 (C 13), 134.9 (C 9), 137.3 (CIO), 146.7 (C 6 )

7a 12.0 (C19), 16.8 (C20), 21.6 (C18), 22.9 (C3), 28.3 (C 16), 28.3 (C17), 35.8 (C l) ,40.7 (C2), 43.1 (C 14), 60.5 (C15), 120.0 (C7), 118.1 ( C l l ) , 127.8 (C 4), 128.3 (C 12), 128.3 (C 8 ), 129.2 (C 5), 129.9 (C13), 134.9 (C 9), 135.5 (CIO), 146.7 (C6)

a 70 eV; b 400 MHz, CDC13, ppm, d relative to Me4Si; c 100 MHz, CDC13, ppm, d relative to Me4Si; * inter­changeable values.

Na2S 0 4 and subsequently concentrated under re­duced pressure. S i02 column chromatography (EtOAc/hexane 6/4) afforded 56 mg (80%) of 4- oxoretinal, which was chemoselectively reduced to 3 with 90% yield using lithium tris[(3-ethyl-3-pen- tyl)oxy]aluminium hydride according to [11] (spectroscopic data, cf Table II).

5,6-Epoxyretinol (4), 5,8-epoxyretinol (5) and 3-dehydroretinol (6)

Epoxyretinols 4 and 5 were synthesized as de­scribed [12] and their identities were confirmed by NMR spectroscopy [13], The synthesis of 6 was performed as described [14] and the product char­acterized by NMR spectroscopy [15].

Table IV. Spectroscopic data of all-E-(8)- and 12-Z- (7a) anhydroretinol.

U V (M eO H ) [Amax] 8 346, 366, 388 nm (e 54500)8 a -270, 344, 364, 384 nm (e 54500)

EI-MSa [m/z(%)] M+ 268 (31), 197 (15), 161 (15), 145 (46), 119 (55), 105 (70), 91 (69), 41 (100)

'H NM R b [<3] 8 1.31 (s, 3H , H-16), 1.31 (s, 3H , H-17), -1 .52 (m, 2H , H-2), 1.91 (s, 3H , H-18),1.91 (s*, 3 H, H-19), 1.95 (s*. 3H , H-20), -2 .17 (m, 2 H, H-3), 5.02 (d, 1 H, 7 = 10.6, H(Z)-15), 5.20 (d, 1 H, 7 = 17.3, H(E)-15),5.78 (t, 1H, 7, = 4.4, Jz = 8.7, H-4), 6.19 (d, 1H , 7 = 11.0, H-12), 6.42 (d, 1H, 7 =11.1, H-7), 6.44 (d, 1H, 7 = 14.5, H-10),6.46 (t, 2H , 7j = 10.5, J2 = 17.2, H-14),6.61 (dd, 1H, 7, = 11.3, 72 = 14.9, H - ll) ,6.79 (d, 1 H, 7 = 11.4, H-8 )

8 a 1.31 (s, 3H , H-16), 1.31 (s, 3H , H-17), -1 .52 (m, 2H , H-2), 1.91 (s, 3H . H-18),1.91 (s*, 3H , H-19), 1.95 (s*, 3H , H-20), -2 .17 (m, 2H , H-3), 5.01 (d, 1 H, 7 = 10.6, H (Z)-15), 5.19 (d, 1H, 7 = 17.3, H(E)-15),5.78 (t, 1H, 7, = 4.4, J2 = 8.7, H-4), 6.19 (d, 1 H, 7 = 11.0, 11-12), 6.42 (d. 1 H. 7 =11.1. H-7), 6.44 (d, 1H. 7 = 14.5, H-10),6.46 (t, 2H , 7, = 10.5, J2 = 17.2, H-14),6.61 (dd, 1 H, 7, = 11.3, J2 = 14.9, H - ll) ,6.79 (d. 1H, 7 = 11.4, H-8 )

13C NM RC [<3] 8 11.9 (C 19), 11.9 (C20), 21.2 (C18), 22.0 (C 3), 28.5 (C 16), 28.5 (C17), 34.6 (C l) ,40.4 (C 2), 112.0 (C 15), 120.3 (C 7), 123.9 ( C l l ) , 128.5 (C4), 130.0 (C 8 ), 132.4 (C 12), 134.4 (C 5), 135.6 (C 9), 135.0 (C 13), 139.3 (CIO), 141.4 (C14), 146.1 (C 6)

8 a 11.9 (C 19), 16.0 (C20), 21.2 (C18), 23.8 (C 3), 27.9 (C 16), 27.9 (C17), 36.2 (C l), 37.0 (C 2), 111.8 (C 15), 118.4 ( C l l ) ,118.6 (C 7), 128.1 (C 4), 130.2 (C 8 ), 133.4 (C 12), 134.3 (C 5), 134.7 (C13), 135.6 (C 9), 138.2 (CIO), 141.2 (C14), 146.0 (C 6 )

a 70 eV; b 400 MHz, CDC13, ppm, d relative to Me4Si; c 100 MHz, CDCI3, ppm, d relative to Me4Si; * inter­changeable values.

all-E-(7) and 12-Z-(7a) Retroretinol

According to [16] acid-catalyzed isomerization of retinyl acetate delivered retroretinyl acetate. Its saponification with 10% ethanolic KOH quantita­tively yielded 7; approximately 10% of (7) iso- merized spontaneously to 7 a (spectroscopic data, cf. Table III).

all-E-(8) and 12-Z-(8si) Anhydroretinol

According to [16] retinol was converted to anhy­droretinol (8) in isopropanol water (pH 2) mix­ture; approximately 15% of purified 8 (S i0 2; EtOAc/hexane 85/15) spontaneously isomerized to 8a (spectroscopic data cf. Table IV).

592 D. W aldm ann et al. ■ Iron (III)P orph inate /H 2Q 2-M ediated Conversion of A lI-(£')-Retinol

Nuclear magnetic resonance (NMR)

'H and 13C NMR spectra were recorded on Bruker AC 200 and AC 400 instruments using CDCI3 as solvent and Me4Si as reference standard. 2D-NM R experiments were carried out using the Bruker standard procedures.

Results and Discussion

Complete (>98%) (Fe3+-TPP)/H20 2 catalyzed conversion of all-(£')-retinol (1) was achieved after 24 h and yielded a number of products whose sep­aration was performed by combination of both re­versed phase and normal phase HPLC analyses. Fig. 1 shows the HPLC separations of the products formed. As major non-volatile products 4-hydroxy- retinol (2), 4-oxoretinol (3), 5,8-epoxyretinol (4),5,6-epoxyretinol (5), 3-dehydroretinol (6 ), all-(£)- and 12-(Z)-retroretinol (7/7a), and all-(£')- and 12-(Z)-anhydroretinol (8/8 a) were identified by comparison of their chromatographic and spectro-

Rt [min]

Fig. 1. HPLC separations of the non-volatile products formed from retinol (1) by Fe3+-TPP/H20 2 catalysis on Eurospher 100 C-18 [(i) (ii)] and on Lichrospher Si 100 [(iii)] columns (cf. Materials and Methods). 2 4-hydroxy- retinol 3 4-oxoretinol 4 5,8-epoxyretinol 5 5,6-epoxyreti- nol 6 3-dehydroretinol 7/7a all-(£')- and 12-(Z)-retroreti- nol 8/8a all-(£)- and 12-(Z)-anhydroretinol.

Fig. 2. Structures of non-volatile products formed from retinol (1) by Fe3+-TPP/H20 2 catalysis (cf. Fig. 1).

scopic data with those of synthesized reference substances (Fig. 1 and 2). In addition, several short-chain oxygenated compounds were iden­tified by HRGC-MS analysis, i.e. 1,6,6-trimethyl-2-hydroxy-cyclohexanone, ß-cyclocitral, /3-ionone.5,6-epoxy-/3-ionone and dihydroactinidiolide. Some minor volatile compounds remained un­identified.

The doubtless assignment of the two rearranged products 7 and 8 as well as the differentiation of their (£/Z)-isomers was only possible by means of 13C NMR spectroscopy. Neither for 7 nor for 8 complete NMR data were available in the litera­ture. We therefore performed an INADEQUATE- 2D-NM R experiment with 8, in order to reveal all the assignments of the twenty carbon atoms [13]. With this 2D-NM R method unambiguous assign­ment of the full sequence of carbon atoms includ­ing ring size, position of double bonds and methyl groups was achieved. By comparison with data published previously for (£/Z)-isomers of reti­noids the structures of the all-(£') and 12-(Z)-iso- mers (7/7 a; 8/8 a) were elucidated [17,18].

D. W aldm ann et al. • Iron(III)Porphinate/H 202-M ediated C onversion of A ll-(£ ')-R etinol 593

Table V. Distribution of the major products formed from retinol ( l ) a by Fe3+-TPP/H20 2 catalysis.

Product Amount [wg]

Non-volatile productsb4-Hydroxyretinol (2) 654-Oxoretinol (3) 705,8-Epoxyretinol (4) 555,6-Epoxyretinol (5) 653-Dehydroretinol (6) 35Retroretinol [all-(£)+12-(Z)] (7a/7b) 100Anhydroretinol [all-(£)+12-(Z)] (8a/8b) 95Volatile productsc2,6,6-Trimethyl-2-hydroxy-cyclohexanone 8ß-Cyclocitral 6/3-Ionone 425,6-Epoxy-/3-ionone 76Dihydroactinidiolide 131

a 10 mg (6.9 mM) (1); b HPLC determination using reference solutions of known concentrations; c HRGC determination by means of external standard (1-butanol; F - 1.0).

Scheme 1.

Product quantification was limited by the in­complete HPLC separations (cf. Fig. 1). In addi­tion, approximately 25% of 1 was not recovered among the conversion products. Thus, the data represented in Table V have to be regarded under these restrictions. Similar incomplete balances have been reported recently by several authors during carotenoid degradation studies [19,20].

As to the potential formation pathways of the main products formed during (Fe3+-TPP)-H20 2- catalyzed conversion of 1 there is sufficient infor­mation from the literature to consider a C4 cen­tered radical ( la ) as the key intermediate during conversion of 1 by iron(III)porphinates [21-23] (cf. Scheme I; >FeIII+ represents an iron(III)- porphyrin cation). According to [22,23] the C4 peroxyl radical formed from l a by reaction with oxygen attacks the 5,6-double bond yielding 5,6- epoxyretinol (5) that easily rearranges to 5,8-ep- oxyretinol (4). 4-Hydroxyretinol (2) may be gener­

ated by homolytic cleavage of the O -O -bond of the peroxyl radical and subsequent attack of H atom. Dehydration of 2 results in the formation of3-dehydroretinol (6). The production of 4-oxoreti- nol (3) can be explained by the attack of an inter­mediate hydroperoxyl radical [24] and subsequent dehydration. Finally, solvent effects of radical sta­bilization might be responsible for the production of the rearranged substances 7/7 a and 8/8 a. The abstraction of the proton from C4 [16] leads to the generation of retroretinol (7); subsequent de­hydration forms the anhydroretinol (8).

AcknowledgementsThis work was gratefully supported by the

Deutsche Forschungsgemeinschaft, Bonn (SFB 347) and the Fonds der Chemischen Industrie. E. Ruckdeschel and Dr. Scheutzow (Institut für O r­ganische Chemie) are thanked for recording the NMR spectra and helpful discussions.

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