P-Ionol

C21H26N2O5 2122-39-6) see Vincamine vinylene carbonate (C,H203 872-36-6) see Bisantrene vinyl-p-ionol... 

Generally for simple alkenes the E-isomer is thermodynamically more stable than the Z-isomer. Photochemical isomerization is thus a powerful method to obtain Z-alkenes in good yields, as shown for p-ionol (3.3) 308). 

This French group patented a process for the preparation of vitamin A from vinyl-P-ionol, by BF3-Et20 catalyzed condensation with a C5 sulphide (50% yield) [58]. 

As shown in Scheme 1, isotretinoin (1) was first synthesized by Garbers et al. in 1968 utilizing a key Wittig condensation. Phosphonium salt 8 was prepared from direct treatment of vinyl p-ionol 7 with triphenylphosphonium bromide (PhsPaHBr) in ethanol. Subsequent addition of an excess of sodium ethoxide to 8 was followed by an ethanol solution of cij-3-formyl crotonic acid (9) to produce isotretinoin (1,2-cjs-vitamin A acid. 

The oxidation of various secondary alcohols, including the allylic alcohols carveol (5) and P-ionol (4), leads to the corresponding ketones in 70-80 % yield (Eq. (3), Table 7). Oxidation of (—)-carveol (J) with nickel peroxide (2.5 eq., 50 °C, benzene) yielded only 33 % ketone. 

Ethynyl-p-ionol Dimethyl sulfoxide Ethyl bromide Copper chloride Alumina (Alcoa F-20)... 

Ethynyl-beta-ionol has been converted to its lower alkyl ethers by use of alkyl sulfates, using an aprotic solvent such as dimethyl sulfoxide (DMSO) or dimethyl formamide (DMF) in a basic medium, using a base such as NaOH or Ba(OH)2.The yields around 90%. In one example, the following components were used ethynyl-p-ionol 65.7 g (0.3 mole) ethyl sulfate 138.6 g (0.9 mole) sodium hydroxide (97%) pellets 37.0 g (0.9 mole) dimethyl sulfoxide 200 ml. 

The infrared spectrum of the product obtained showed the presence of the acetate group and the ether group. Its ultraviolet spectrum showed a single maximum at 236 mp, characteristic of the p-ionol group diene. The reaction... 

Figure 1. Synthesis of 4-hydroxy-7,8-dihydro-P-ionol (4) from 4-oxo-P-ionol (2) via 4-oxo-7,8-dihydro-P-ionol (3).

Figure 4. Structures of thermal degradation products of 3-hydroxy-P-ionol (9) under SDE conditions (100°Cj pH 3.7). 5 cf. Fig. 3 6 2,2,6,7-tetramethyl-bi-cyclo- [4.3.0]nona-4,9(l)-dien-8-oli 7 = 3,4-didehydro-P-ionoli 13 = megastigma-5,7,9-trien-3-oli 14 mega-stigma-4, 6,8-trien-3-ol 15 > 2,2,6,7-tetramethyl-bi cyclo[4.3.0]nona-7,9(1)-di en-4-ol.

Figure 6. Structures of aglycones released from quince fruit extract after glycosidase (emulsin) treatment. 9 - 3-hydroxy-0-ionol 18 3-hydroxy- 3-ionone 19 > 3-oxo-o-ionol 20 = 3-hydroxy-7,8-dihydro-P-ionol 21 vomifoliol 22 = 7,8-dihydrovomifoliol.

The synthesis of vitamin A was certainly a pioneering work in the industrial application of the Wittig reaction 6). The decisive step in this synthesis performed by the BASF, which had already established a plant for the production of vitamin A in 1971 2S4), is the Wittig olefination of vinyl-P-ionol 503 with y-formylcrotyl acetate 507 to vitamin A acetate 508. The phosphonium salt 505 is obtained by reaction of the alcohol 503 with triphenylphosphine hydrobromide 504 2S5) (Scheme 85). 

The name of one-way isomerization was used by Ramamurthy and Liu in 1976 in the triplet-sensitized isomerization of an olefin related to vitamin A [51]. P-Ionol (3) underwent cis-trans isomerization on triplet sensitization with high-... 

Thus, the concept of one-way isomerization on sensitized isomerization of P-ionol 3 appeared several years before the finding of the typical one-way isomerization in 2-anthrylethenes (2). 

Figure 4.2. Principal norisoprenoid compounds in grape and wine. (29) TDN (1,1,6-trimethyl-l,2-dihydronaphthalene) (30) P-damascone (31) P-damascenone (32) vom-ifoliol (33) dihydrovomifoliol (34) 3-hydroxy-P-damascone (35) 3-oxo-a-ionol (36) 3-hydroxy-7,8-dihydro-P-ionol (37) oc-ionol (38) P-ionol (39) a-ionone (40) P-ionone (41) actinidols (42) vitispiranes (spiro [4.5]-2,10,10-trimethyl-6-methylene-l-oxa-7-decene) (43) Riesling acetal (2,2,6-tetramethyl-7,ll-dioxatricyclo[6.2.1.01,6] undec-4-ene).

Figure 4.8. The GC/MS-EI (70eV) SCAN mode chromatogram of compounds formed by acid hydrolysis of a Raboso grape skins extract. Peak 1. frans-furanlinalool oxide peak 2. cfs-furanlinalool oxide I.S.l, internal standard (1-octanol) peak 3. (Z)-ocimenol peak 4. ( )-ocimenol peak 5. a-terpineol I.S.2, internal standard (1-decanol) peak 6. 2-exo-hydroxy-l,8-cineol peak 7. benzyl alcohol peak 8. P-phenylethanol peak 9. actinidols A peak 10. actinidols B peak 11. endiol peak 12. eugenol peak 13. vinylguaiacol peak 14. p-menthenediol I peak 15. 3-hydroxy-P-damascone peak 16. vanillin peak 17. methyl vanillate peak 18. 3-oxo-a-ionol peak 19. 3-hydroxy-7,8-dihydro-P-ionol peak 20. homovanillic alcohol peak 21. vomifoliol.

By reaction of the Cg-hydroxyketone (3R)-58 with isopropenyl methyl ether, the acetonide 59 was obtained. Subsequent reaction with but-3-yn-2-ol (60), acetylation and dehydration gave the diacetate 61 which was reduced with sodium bis-(2-methoxyethoxy)aluminium hydride (SMEAH) to (3/ )-3-hydroxy-p-ionol (62) Scheme 15). 

Buten-2-oI, 4-(3-hydroxy-2,6,6-trimethyI-1-cycIohexen-1-yI)- 3-hydroxy-p-ionol 1364 1156, 1251,4090 ... 

Fujimori, T., R. Kasuga, H. Kaneko, and M. Noguchi Isolation of 3-hydroxy-P-ionol from hurley tobacco Agr. Biol. Chem. Japan 39 (1975) 913-914. 

M. Noguchi Isolation of a new tobacco constituent, (3S,5R,6S,9E)-3-hydroxy-5,6-epoxy-P-ionol, from 3862c. 

Buten-2-ol, 4-(4-hydroxy-2,6,6-trimethyl-1 -cyclohexen-1 -yl)- 4-hydroxy-P-ionol II.A-5... 

There are numerous applications of acetylides in the preparation of a-hydroxyalkynes, the following being illustrative of the general procedures. For the preparation of ethynyl-p-ionol (2), a key carotenoid building block, P-ionone (i) is condensed with ethynyl magnesium bromide (4) in ether [2], or with lithium acetylide (5) in liquid ammonia [7], in 87% and 75% yields, respectively (Scheme 1). The lower yield obtained with lithium acetylide probably reflects the propensity of P-ionone (3) to enolize under the reaction conditions. 

Of particular importance for the synthesis of carotenoids is the preparation of vinyl alcohols by the condensation of aldehydes and ketones with vinyl magnesium halides, frequently the commercially available bromides, in THF [12]. The reaction is conducted by adding a solution of the aldehyde or ketone in anhydrous THF to the vinyl Grignard reagent in THF below 0°C, and is exemplified by the preparation of the vinyl-p-ionols 20 [13] and 27 [14] from p-ionone (3) and (3/ )-3-hydroxy-p-ionone (22), respectively (Scheme 6). Table 2 lists some vinyl alcohols that have been prepared from vinyl magnesium halides. 

The units 49 and 50 used in the synthesis of vitamin A are also used in many ways in carotenoid syntheses and are produced industrially in large scale. p-Ionone (17) can be converted into vinyl-p-ionol (51) by ethynylation to 52 and partial hydrogenation [42]. This conversion is also achieved in one step by 1,2-addition of vinylmagnesium chloride 55[43]. The two routes are, in principle, equivalent, and which one is used in practice is decided by conditions on site. In this example, the main considerations are the availability of acetylene (4) and vinyl chloride, operating experience, and permits for handling these materials. The Ci5-phosphonium salt 49 is formed directly from 51 by the action of triphenylphosphine and acid [44,45]. A step involving labile P-ionylidene-ethyl halide is thus avoided. Crystalline (lE,9E)-49 is obtained in excellent yield by reaction of 51 with triphenylphosphine and sulphuric acid in isopropanol/heptane [46]. 

---